Bio


Dill has interests in computational systems biology as well as the theory and application of formal verification techniques to system designs, which encompass hardware, protocols, and software. He has also done research in asynchronous circuit verification and synthesis, and in verification methods for hard real-time systems.

Academic Appointments


Honors & Awards


  • Pioneer Award, Electronic Frontier Foundation
  • Fellow, IEEE
  • Fellow, ACM
  • Member, National Academy of Engineering (2013)
  • Fellow, American Academy of Arts and Sciences (2013)

Professional Education


  • PhD, Carnegie Mellon (1987)

Current Research and Scholarly Interests


Computational methods for understanding regulatory circuits in cell biology

2017-18 Courses


Graduate and Fellowship Programs


  • Biomedical Informatics (Phd Program)

All Publications


  • Systematic discovery of mutation-specific synthetic lethals by mining pan-cancer human primary tumor data. Nature communications Sinha, S., Thomas, D., Chan, S., Gao, Y., Brunen, D., Torabi, D., Reinisch, A., Hernandez, D., Chan, A., Rankin, E. B., Bernards, R., Majeti, R., Dill, D. L. 2017; 8: 15580-?

    Abstract

    Two genes are synthetically lethal (SL) when defects in both are lethal to a cell but a single defect is non-lethal. SL partners of cancer mutations are of great interest as pharmacological targets; however, identifying them by cell line-based methods is challenging. Here we develop MiSL (Mining Synthetic Lethals), an algorithm that mines pan-cancer human primary tumour data to identify mutation-specific SL partners for specific cancers. We apply MiSL to 12 different cancers and predict 145,891 SL partners for 3,120 mutations, including known mutation-specific SL partners. Comparisons with functional screens show that MiSL predictions are enriched for SLs in multiple cancers. We extensively validate a SL interaction identified by MiSL between the IDH1 mutation and ACACA in leukaemia using gene targeting and patient-derived xenografts. Furthermore, we apply MiSL to pinpoint genetic biomarkers for drug sensitivity. These results demonstrate that MiSL can accelerate precision oncology by identifying mutation-specific targets and biomarkers.

    View details for DOI 10.1038/ncomms15580

    View details for PubMedID 28561042

  • Cell cycle progression in Caulobacter requires a nucleoid-associated protein with high AT sequence recognition PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Ricci, D. P., Melfi, M. D., Lasker, K., Dill, D. L., McAdams, H. H., Shapiro, L. 2016; 113 (40): E5952-E5961

    Abstract

    Faithful cell cycle progression in the dimorphic bacterium Caulobacter crescentus requires spatiotemporal regulation of gene expression and cell pole differentiation. We discovered an essential DNA-associated protein, GapR, that is required for Caulobacter growth and asymmetric division. GapR interacts with adenine and thymine (AT)-rich chromosomal loci, associates with the promoter regions of cell cycle-regulated genes, and shares hundreds of recognition sites in common with known master regulators of cell cycle-dependent gene expression. GapR target loci are especially enriched in binding sites for the transcription factors GcrA and CtrA and overlap with nearly all of the binding sites for MucR1, a regulator that controls the establishment of swarmer cell fate. Despite constitutive synthesis, GapR accumulates preferentially in the swarmer compartment of the predivisional cell. Homologs of GapR, which are ubiquitous among the α-proteobacteria and are encoded on multiple bacteriophage genomes, also accumulate in the predivisional cell swarmer compartment when expressed in Caulobacter The Escherichia coli nucleoid-associated protein H-NS, like GapR, selectively associates with AT-rich DNA, yet it does not localize preferentially to the swarmer compartment when expressed exogenously in Caulobacter, suggesting that recognition of AT-rich DNA is not sufficient for the asymmetric accumulation of GapR. Further, GapR does not silence the expression of H-NS target genes when expressed in E. coli, suggesting that GapR and H-NS have distinct functions. We propose that Caulobacter has co-opted a nucleoid-associated protein with high AT recognition to serve as a mediator of cell cycle progression.

    View details for DOI 10.1073/pnas.1612579113

    View details for Web of Science ID 000384528900022

    View details for PubMedID 27647925

  • A Pharmacogenetic Discovery: Cystamine Protects Against Haloperidol-Induced Toxicity and Ischemic Brain Injury GENETICS Zhang, H., Zheng, M., Wu, M., Xu, D., Nishimura, T., Nishimura, Y., Giffard, R., Xiong, X., Xu, L. J., Clark, J. D., Sahbaie, P., Dill, D. L., Peltz, G. 2016; 203 (1): 599-?

    Abstract

    Haloperidol is an effective antipsychotic agent, but it causes Parkinsonian-like extrapyramidal symptoms in the majority of treated subjects. To address this treatment-limiting toxicity, we analyzed a murine genetic model of haloperidol-induced toxicity (HIT). Analysis of a panel of consomic strains indicated that a genetic factor on chromosome 10 had a significant effect on susceptibility to HIT. We analyzed a whole-genome SNP database to identify allelic variants that were uniquely present on chromosome 10 in the strain that was previously shown to exhibit the highest level of susceptibility to HIT. This analysis implicated allelic variation within pantetheinase genes (Vnn1 and Vnn3), which we propose impaired the biosynthesis of cysteamine, could affect susceptibility to HIT. We demonstrate that administration of cystamine, which is rapidly metabolized to cysteamine, could completely prevent HIT in the murine model. Many of the haloperidol-induced gene expression changes in the striatum of the susceptible strain were reversed by cystamine coadministration. Since cystamine administration has previously been shown to have other neuroprotective actions, we investigated whether cystamine administration could have a broader neuroprotective effect. Cystamine administration caused a 23% reduction in infarct volume after experimentally induced cerebral ischemia. Characterization of this novel pharmacogenetic factor for HIT has identified a new approach for preventing the treatment-limiting toxicity of an antipsychotic agent, which could also be used to reduce the extent of brain damage after stroke.

    View details for DOI 10.1534/genetics.115.184648

    View details for Web of Science ID 000376012100040

    View details for PubMedID 26993135

    View details for PubMedCentralID PMC4858802

  • The multiple PDZ domain protein Mpdz/MUPP1 regulates opioid tolerance and opioid-induced hyperalgesia BMC GENOMICS Donaldson, R., Sun, Y., Liang, D., Zheng, M., Sahbaie, P., Dill, D. L., Peltz, G., Buck, K. J., Clark, J. D. 2016; 17

    Abstract

    Opioids are a mainstay for the treatment of chronic pain. Unfortunately, therapy-limiting maladaptations such as loss of treatment effect (tolerance), and paradoxical opioid-induced hyperalgesia (OIH) can occur. The objective of this study was to identify genes responsible for opioid tolerance and OIH.These studies used a well-established model of ascending morphine administration to induce tolerance, OIH and other opioid maladaptations in 23 strains of inbred mice. Genome-wide computational genetic mapping was then applied to the data in combination with a false discovery rate filter. Transgenic mice, gene expression experiments and immunoprecipitation assays were used to confirm the functional roles of the most strongly linked gene. The behavioral data processed using computational genetic mapping and false discovery rate filtering provided several strongly linked biologically plausible gene associations. The strongest of these was the highly polymorphic Mpdz gene coding for the post-synaptic scaffolding protein Mpdz/MUPP1. Heterozygous Mpdz +/- mice displayed reduced opioid tolerance and OIH. Mpdz gene expression and Mpdz/MUPP1 protein levels were lower in the spinal cords of low-adapting 129S1/Svlm mice than in high-adapting C57BL/6 mice. Morphine did not alter Mpdz expression levels. In addition, association of Mpdz/MUPP1 with its known binding partner CaMKII did not differ between these high- and low-adapting strains.The degrees of maladaptive changes in response to repeated administration of morphine vary greatly across inbred strains of mice. Variants of the multiple PDZ domain gene Mpdz may contribute to the observed inter-strain variability in tolerance and OIH by virtue of changes in the level of their expression.

    View details for DOI 10.1186/s12864-016-2634-1

    View details for Web of Science ID 000375079200001

    View details for PubMedID 27129385

  • CauloBrowser: A systems biology resource for Caulobacter crescentus. Nucleic acids research Lasker, K., Schrader, J. M., Men, Y., Marshik, T., Dill, D. L., McAdams, H. H., Shapiro, L. 2016; 44 (D1): D640-5

    Abstract

    Caulobacter crescentus is a premier model organism for studying the molecular basis of cellular asymmetry. The Caulobacter community has generated a wealth of high-throughput spatiotemporal databases including data from gene expression profiling experiments (microarrays, RNA-seq, ChIP-seq, ribosome profiling, LC-ms proteomics), gene essentiality studies (Tn-seq), genome wide protein localization studies, and global chromosome methylation analyses (SMRT sequencing). A major challenge involves the integration of these diverse data sets into one comprehensive community resource. To address this need, we have generated CauloBrowser (www.caulobrowser.org), an online resource for Caulobacter studies. This site provides a user-friendly interface for quickly searching genes of interest and downloading genome-wide results. Search results about individual genes are displayed as tables, graphs of time resolved expression profiles, and schematics of protein localization throughout the cell cycle. In addition, the site provides a genome viewer that enables customizable visualization of all published high-throughput genomic data. The depth and diversity of data sets collected by the Caulobacter community makes CauloBrowser a unique and valuable systems biology resource.

    View details for DOI 10.1093/nar/gkv1050

    View details for PubMedID 26476443

  • CauloBrowser: A systems biology resource for Caulobacter crescentus. Nucleic acids research Lasker, K., Schrader, J. M., Men, Y., Marshik, T., Dill, D. L., McAdams, H. H., Shapiro, L. 2016; 44 (D1): D640-5

    View details for DOI 10.1093/nar/gkv1050

    View details for PubMedID 26476443

  • Towards in vivo estimation of reaction kinetics using high-throughput metabolomics data: a maximum likelihood approach BMC SYSTEMS BIOLOGY Zhang, W., Kolte, R., Dill, D. L. 2015; 9

    View details for DOI 10.1186/s12918-015-0214-7

    View details for Web of Science ID 000362397100001

    View details for PubMedID 26437964

  • The role of Abcb5 alleles in susceptibility to haloperidol-induced toxicity in mice and humans. PLoS medicine Zheng, M., Zhang, H., Dill, D. L., Clark, J. D., Tu, S., Yablonovitch, A. L., Tan, M. H., Zhang, R., Rujescu, D., Wu, M., Tessarollo, L., Vieira, W., Gottesman, M. M., Deng, S., Eberlin, L. S., Zare, R. N., Billard, J., Gillet, J., Li, J. B., Peltz, G. 2015; 12 (2)

    Abstract

    We know very little about the genetic factors affecting susceptibility to drug-induced central nervous system (CNS) toxicities, and this has limited our ability to optimally utilize existing drugs or to develop new drugs for CNS disorders. For example, haloperidol is a potent dopamine antagonist that is used to treat psychotic disorders, but 50% of treated patients develop characteristic extrapyramidal symptoms caused by haloperidol-induced toxicity (HIT), which limits its clinical utility. We do not have any information about the genetic factors affecting this drug-induced toxicity. HIT in humans is directly mirrored in a murine genetic model, where inbred mouse strains are differentially susceptible to HIT. Therefore, we genetically analyzed this murine model and performed a translational human genetic association study.A whole genome SNP database and computational genetic mapping were used to analyze the murine genetic model of HIT. Guided by the mouse genetic analysis, we demonstrate that genetic variation within an ABC-drug efflux transporter (Abcb5) affected susceptibility to HIT. In situ hybridization results reveal that Abcb5 is expressed in brain capillaries, and by cerebellar Purkinje cells. We also analyzed chromosome substitution strains, imaged haloperidol abundance in brain tissue sections and directly measured haloperidol (and its metabolite) levels in brain, and characterized Abcb5 knockout mice. Our results demonstrate that Abcb5 is part of the blood-brain barrier; it affects susceptibility to HIT by altering the brain concentration of haloperidol. Moreover, a genetic association study in a haloperidol-treated human cohort indicates that human ABCB5 alleles had a time-dependent effect on susceptibility to individual and combined measures of HIT. Abcb5 alleles are pharmacogenetic factors that affect susceptibility to HIT, but it is likely that additional pharmacogenetic susceptibility factors will be discovered.ABCB5 alleles alter susceptibility to HIT in mouse and humans. This discovery leads to a new model that (at least in part) explains inter-individual differences in susceptibility to a drug-induced CNS toxicity.

    View details for DOI 10.1371/journal.pmed.1001782

    View details for PubMedID 25647612

    View details for PubMedCentralID PMC4315575

  • The role of abcb5 alleles in susceptibility to haloperidol-induced toxicity in mice and humans. PLoS medicine Zheng, M., Zhang, H., Dill, D. L., Clark, J. D., Tu, S., Yablonovitch, A. L., Tan, M. H., Zhang, R., Rujescu, D., Wu, M., Tessarollo, L., Vieira, W., Gottesman, M. M., Deng, S., Eberlin, L. S., Zare, R. N., Billard, J., Gillet, J., Li, J. B., Peltz, G. 2015; 12 (2)

    View details for DOI 10.1371/journal.pmed.1001782

    View details for PubMedID 25647612

  • Mutant WT1 is associated with DNA hypermethylation of PRC2 targets in AML and responds to EZH2 inhibition. Blood Sinha, S., Thomas, D., Yu, L., Gentles, A. J., Jung, N., Corces-Zimmerman, M. R., Chan, S. M., Reinisch, A., Feinberg, A. P., Dill, D. L., Majeti, R. 2015; 125 (2): 316-326

    Abstract

    Acute myeloid leukemia (AML) is associated with deregulation of DNA methylation; however, many cases do not bear mutations in known regulators of CpG methylation. We found that mutations in WT1, IDH2, and CEBPA were strongly linked to DNA hypermethylation in AML using a novel integrative analysis of TCGA data based on Boolean implications, if-then rules that identify all individual CpG sites that are hypermethylated in the presence of a mutation. Introduction of mutant WT1 (WT1mut) into wildtype AML cells induced DNA hypermethylation, confirming mutant WT1 to be causally associated with DNA hypermethylation. Methylated genes in WT1mut primary patient samples were highly enriched for polycomb repressor complex 2 (PRC2) targets, implicating PRC2 dysregulation in WT1mut leukemogenesis. We found that PRC2 target genes were aberrantly repressed in WT1mut AML, and that expression of mutant WT1 in CD34+ cord blood cells induced myeloid differentiation block. Treatment of WT1mut AML cells with shRNA or pharmacologic PRC2/EZH2 inhibitors promoted myeloid differentiation, suggesting EZH2 inhibitors may be active in this AML subtype. Our results highlight a strong association between mutant WT1 and DNA hypermethylation in AML, and demonstrate that Boolean implications can be used to decipher mutation-specific methylation patterns that may lead to therapeutic insights.

    View details for DOI 10.1182/blood-2014-03-566018

    View details for PubMedID 25398938

  • The global regulatory architecture of transcription during the Caulobacter cell cycle. PLoS genetics Zhou, B., Schrader, J. M., Kalogeraki, V. S., Abeliuk, E., Dinh, C. B., Pham, J. Q., Cui, Z. Z., Dill, D. L., McAdams, H. H., Shapiro, L. 2015; 11 (1)

    Abstract

    Each Caulobacter cell cycle involves differentiation and an asymmetric cell division driven by a cyclical regulatory circuit comprised of four transcription factors (TFs) and a DNA methyltransferase. Using a modified global 5' RACE protocol, we globally mapped transcription start sites (TSSs) at base-pair resolution, measured their transcription levels at multiple times in the cell cycle, and identified their transcription factor binding sites. Out of 2726 TSSs, 586 were shown to be cell cycle-regulated and we identified 529 binding sites for the cell cycle master regulators. Twenty-three percent of the cell cycle-regulated promoters were found to be under the combinatorial control of two or more of the global regulators. Previously unknown features of the core cell cycle circuit were identified, including 107 antisense TSSs which exhibit cell cycle-control, and 241 genes with multiple TSSs whose transcription levels often exhibited different cell cycle timing. Cumulatively, this study uncovered novel new layers of transcriptional regulation mediating the bacterial cell cycle.

    View details for DOI 10.1371/journal.pgen.1004831

    View details for PubMedID 25569173

  • The Global Regulatory Architecture of Transcription during the Caulobacter Cell Cycle. PLoS genetics Zhou, B., Schrader, J. M., Kalogeraki, V. S., Abeliuk, E., Dinh, C. B., Pham, J. Q., Cui, Z. Z., Dill, D. L., McAdams, H. H., Shapiro, L. 2015; 11 (1)

    View details for DOI 10.1371/journal.pgen.1004831

    View details for PubMedID 25569173

  • Towards in vivo estimation of reaction kinetics using high-throughput metabolomics data: a maximum likelihood approach. BMC systems biology Zhang, W., Kolte, R., Dill, D. L. 2015; 9: 66-?

    Abstract

    High-throughput assays such as mass spectrometry have opened up the possibility for large-scale in vivo measurements of the metabolome. This data could potentially be used to estimate kinetic parameters for many metabolic reactions. However, high-throughput in vivo measurements have special properties that are not taken into account in existing methods for estimating kinetic parameters, including significant relative errors in measurements of metabolite concentrations and reaction rates, and reactions with multiple substrates and products, which are sometimes reversible. A new method is needed to estimate kinetic parameters taking into account these factors.A new method, InVEst (In Vivo Estimation), is described for estimating reaction kinetic parameters, which addresses the specific challenges of in vivo data. InVEst uses maximum likelihood estimation based on a model where all measurements have relative errors. Simulations show that InVEst produces accurate estimates for a reversible enzymatic reaction with multiple reactants and products, that estimated parameters can be used to predict the effects of genetic variants, and that InVEst is more accurate than general least squares and graphic methods on data with relative errors. InVEst uses the bootstrap method to evaluate the accuracy of its estimates.InVEst addresses several challenges of in vivo data, which are not taken into account by existing methods. When data have relative errors, InVEst produces more accurate and robust estimates. InVEst also provides useful information about estimation accuracy using bootstrapping. It has potential applications of quantifying the effects of genetic variants, inference of the target of a mutation or drug treatment and improving flux estimation.

    View details for DOI 10.1186/s12918-015-0214-7

    View details for PubMedID 26437964

  • MYC through miR-17-92 Suppresses Specific Target Genes to Maintain Survival, Autonomous Proliferation, and a Neoplastic State. Cancer cell Li, Y., Choi, P. S., Casey, S. C., Dill, D. L., Felsher, D. W. 2014; 26 (2): 262-272

    Abstract

    The MYC oncogene regulates gene expression through multiple mechanisms, and its overexpression culminates in tumorigenesis. MYC inactivation reverses turmorigenesis through the loss of distinguishing features of cancer, including autonomous proliferation and survival. Here we report that MYC via miR-17-92 maintains a neoplastic state through the suppression of chromatin regulatory genes Sin3b, Hbp1, Suv420h1, and Btg1, as well as the apoptosis regulator Bim. The enforced expression of miR-17-92 prevents MYC suppression from inducing proliferative arrest, senescence, and apoptosis and abrogates sustained tumor regression. Knockdown of the five miR-17-92 target genes blocks senescence and apoptosis while it modestly delays proliferative arrest, thus partially recapitulating miR-17-92 function. We conclude that MYC, via miR-17-92, maintains a neoplastic state by suppressing specific target genes.

    View details for DOI 10.1016/j.ccr.2014.06.014

    View details for PubMedID 25117713

  • Automated identification of stratifying signatures in cellular subpopulations PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Bruggner, R. V., Bodenmiller, B., Dill, D. L., Tibshirani, R. J., Nolan, G. P. 2014; 111 (26): E2770-E2777
  • Automated identification of stratifying signatures in cellular subpopulations. Proceedings of the National Academy of Sciences of the United States of America Bruggner, R. V., Bodenmiller, B., Dill, D. L., Tibshirani, R. J., Nolan, G. P. 2014; 111 (26): E2770-7

    Abstract

    Elucidation and examination of cellular subpopulations that display condition-specific behavior can play a critical contributory role in understanding disease mechanism, as well as provide a focal point for development of diagnostic criteria linking such a mechanism to clinical prognosis. Despite recent advancements in single-cell measurement technologies, the identification of relevant cell subsets through manual efforts remains standard practice. As new technologies such as mass cytometry increase the parameterization of single-cell measurements, the scalability and subjectivity inherent in manual analyses slows both analysis and progress. We therefore developed Citrus (cluster identification, characterization, and regression), a data-driven approach for the identification of stratifying subpopulations in multidimensional cytometry datasets. The methodology of Citrus is demonstrated through the identification of known and unexpected pathway responses in a dataset of stimulated peripheral blood mononuclear cells measured by mass cytometry. Additionally, the performance of Citrus is compared with that of existing methods through the analysis of several publicly available datasets. As the complexity of flow cytometry datasets continues to increase, methods such as Citrus will be needed to aid investigators in the performance of unbiased--and potentially more thorough--correlation-based mining and inspection of cell subsets nested within high-dimensional datasets.

    View details for DOI 10.1073/pnas.1408792111

    View details for PubMedID 24979804

  • Mining TCGA data using Boolean implications. PloS one Sinha, S., Tsang, E. K., Zeng, H., Meister, M., Dill, D. L. 2014; 9 (7)

    Abstract

    Boolean implications (if-then rules) provide a conceptually simple, uniform and highly scalable way to find associations between pairs of random variables. In this paper, we propose to use Boolean implications to find relationships between variables of different data types (mutation, copy number alteration, DNA methylation and gene expression) from the glioblastoma (GBM) and ovarian serous cystadenoma (OV) data sets from The Cancer Genome Atlas (TCGA). We find hundreds of thousands of Boolean implications from these data sets. A direct comparison of the relationships found by Boolean implications and those found by commonly used methods for mining associations show that existing methods would miss relationships found by Boolean implications. Furthermore, many relationships exposed by Boolean implications reflect important aspects of cancer biology. Examples of our findings include cis relationships between copy number alteration, DNA methylation and expression of genes, a new hierarchy of mutations and recurrent copy number alterations, loss-of-heterozygosity of well-known tumor suppressors, and the hypermethylation phenotype associated with IDH1 mutations in GBM. The Boolean implication results used in the paper can be accessed at http://crookneck.stanford.edu/microarray/TCGANetworks/.

    View details for DOI 10.1371/journal.pone.0102119

    View details for PubMedID 25054200

    View details for PubMedCentralID PMC4108374

  • Mining TCGA Data Using Boolean Implications. PloS one Sinha, S., Tsang, E. K., Zeng, H., Meister, M., Dill, D. L. 2014; 9 (7)

    View details for DOI 10.1371/journal.pone.0102119

    View details for PubMedID 25054200

  • Liquid chromatography/mass spectrometry methods for measuring dipeptide abundance in non-small-cell lung cancer. Rapid communications in mass spectrometry : RCM Wu, M., Xu, Y., Fitch, W. L., Zheng, M., Merritt, R. E., Shrager, J. B., Zhang, W., Dill, D. L., Peltz, G., Hoang, C. D. 2013; 27 (18): 2091-2098

    Abstract

    Metabolomic profiling is a promising methodology of identifying candidate biomarkers for disease detection and monitoring. Although lung cancer is among the leading causes of cancer-related mortality worldwide, the lung tumor metabolome has not been fully characterized.We utilized a targeted metabolomic approach to analyze discrete groups of related metabolites. We adopted a dansyl [5-(dimethylamino)-1-naphthalene sulfonamide] derivatization with liquid chromatography/mass spectrometry (LC/MS) to analyze changes of metabolites from paired tumor and normal lung tissues. Identification of dansylated dipeptides was confirmed with synthetic standards. A systematic analysis of retention times was required to reliably identify isobaric dipeptides. We validated our findings in a separate sample cohort.We produced a database of the LC retention times and MS/MS spectra of 361 dansyl dipeptides. Interpretation of the spectra is presented. Using this standard data, we identified a total of 279 dipeptides in lung tumor tissue. The abundance of 90 dipeptides was selectively increased in lung tumor tissue compared to normal tissue. In a second set of validation tissues, 12 dipeptides were selectively increased.A systematic evaluation of certain metabolite classes in lung tumors may identify promising disease-specific metabolites. Our database of all possible dipeptides will facilitate ongoing translational applications of metabolomic profiling as it relates to lung cancer. Copyright © 2013 John Wiley & Sons, Ltd.

    View details for DOI 10.1002/rcm.6656

    View details for PubMedID 23943330

  • Identification of drug targets by chemogenomic and metabolomic profiling in yeast PHARMACOGENETICS AND GENOMICS Wu, M., Zheng, M., Zhang, W., Suresh, S., Schlecht, U., Fitch, W. L., Aronova, S., Baumann, S., Davis, R., St Onge, R., Dill, D. L., Peltz, G. 2012; 22 (12): 877-886

    Abstract

    To advance our understanding of disease biology, the characterization of the molecular target for clinically proven or new drugs is very important. Because of its simplicity and the availability of strains with individual deletions in all of its genes, chemogenomic profiling in yeast has been used to identify drug targets. As measurement of drug-induced changes in cellular metabolites can yield considerable information about the effects of a drug, we investigated whether combining chemogenomic and metabolomic profiling in yeast could improve the characterization of drug targets.We used chemogenomic and metabolomic profiling in yeast to characterize the target for five drugs acting on two biologically important pathways. A novel computational method that uses a curated metabolic network was also developed, and it was used to identify the genes that are likely to be responsible for the metabolomic differences found.The combination of metabolomic and chemogenomic profiling, along with data analyses carried out using a novel computational method, could robustly identify the enzymes targeted by five drugs. Moreover, this novel computational method has the potential to identify genes that are causative of metabolomic differences or drug targets.

    View details for DOI 10.1097/FPC.0b013e32835aa888

    View details for Web of Science ID 000311031800006

    View details for PubMedID 23076370

  • Computational genetic discoveries that could improve perioperative medicine CURRENT OPINION IN ANESTHESIOLOGY Zheng, M., Dill, D., Clark, J. D., Peltz, G. 2012; 25 (4): 428-433

    Abstract

    The review examines the rationale and translational utility of computational genetic studies using murine models of biomedical traits.Computational genetic mapping studies have identified the genetic basis for biomedical trait differences in 16 different murine models, including several that are of importance to perioperative medicine.The results have generated new treatments for alleviating incisional pain and narcotic drug withdrawal symptoms, which are now in clinical trials. A recent study identified allelic differences affecting chronic pain responses in mice and humans, which may enable a new 'personalized' approach to treating chronic pain.

    View details for DOI 10.1097/ACO.0b013e32835561f9

    View details for Web of Science ID 000306273900005

    View details for PubMedID 22647490

  • Gene Expression Commons: An Open Platform for Absolute Gene Expression Profiling PLOS ONE Seita, J., Sahoo, D., Rossi, D. J., Bhattacharya, D., Serwold, T., Inlay, M. A., Ehrlich, L. I., Fathman, J. W., Dill, D. L., Weissman, I. L. 2012; 7 (7)

    Abstract

    Gene expression profiling using microarrays has been limited to comparisons of gene expression between small numbers of samples within individual experiments. However, the unknown and variable sensitivities of each probeset have rendered the absolute expression of any given gene nearly impossible to estimate. We have overcome this limitation by using a very large number (>10,000) of varied microarray data as a common reference, so that statistical attributes of each probeset, such as the dynamic range and threshold between low and high expression, can be reliably discovered through meta-analysis. This strategy is implemented in a web-based platform named "Gene Expression Commons" (https://gexc.stanford.edu/) which contains data of 39 distinct highly purified mouse hematopoietic stem/progenitor/differentiated cell populations covering almost the entire hematopoietic system. Since the Gene Expression Commons is designed as an open platform, investigators can explore the expression level of any gene, search by expression patterns of interest, submit their own microarray data, and design their own working models representing biological relationship among samples.

    View details for DOI 10.1371/journal.pone.0040321

    View details for Web of Science ID 000306548900020

    View details for PubMedID 22815738

  • Cd14 SNPs regulate the innate immune response MOLECULAR IMMUNOLOGY Liu, H., Hu, Y., Zheng, M., Suhoski, M. M., Engleman, E. G., Dill, D. L., Hudnall, M., Wang, J., Spolski, R., Leonard, W. J., Peltz, G. 2012; 51 (2): 112-127

    Abstract

    CD14 is a monocytic differentiation antigen that regulates innate immune responses to pathogens. Here, we show that murine Cd14 SNPs regulate the length of Cd14 mRNA and CD14 protein translation efficiency, and consequently the basal level of soluble CD14 (sCD14) and type I IFN production by murine macrophages. This has substantial downstream consequences for the innate immune response; the level of expression of at least 40 IFN-responsive murine genes was altered by this mechanism. We also observed that there was substantial variation in the length of human CD14 mRNAs and in their translation efficiency. sCD14 increased cytokine production by human dendritic cells (DCs), and sCD14-primed DCs augmented human CD4T cell proliferation. These findings may provide a mechanism for exploring the complex relationship between CD14 SNPs, serum sCD14 levels, and susceptibility to human infectious and allergic diseases.

    View details for DOI 10.1016/j.molimm.2012.02.112

    View details for Web of Science ID 000304687500002

    View details for PubMedID 22445606

  • A better prognosis for genetic association studies in mice TRENDS IN GENETICS Zheng, M., Dill, D., Peltz, G. 2012; 28 (2): 62-69

    Abstract

    Although inbred mouse strains have been the premier model organism used in biomedical research, multiple studies and analyses have indicated that genome-wide association studies (GWAS) cannot be productively performed using inbred mouse strains. However, there is one type of GWAS in mice that has successfully identified the genetic basis for many biomedical traits of interest: haplotype-based computational genetic mapping (HBCGM). Here, we describe how the methodological basis for a HBCGM study significantly differs from that of a conventional murine GWAS, and how an integrative analysis of its output within the context of other 'omic' information can enable genetic discovery. Consideration of these factors will substantially improve the prognosis for the utility of murine genetic association studies for biomedical discovery.

    View details for DOI 10.1016/j.tig.2011.10.006

    View details for Web of Science ID 000300532200002

    View details for PubMedID 22118772

  • Cd14 SNPs regulate the innate immune response Molecular Immunology Lu, H., Hu, Y., Zheng, M., Engleman, E., Dill, D., Hudnall, M. 2012; 2 (51): 112–127
  • Computational genetic discoveries that could improve perioperative medicine Current Opinion in Anesthesiology Zheng, M., Dill, D., Clark, J., Peltz, G. 2012
  • Gene Expression Commons: an open platform for absolute gene expression profiliing PLoS One Seita, J., Sahoo, D., Rossi, D., Bhattacharya, D., Serwold, T., Inlay, M., Dill, D. 2012; 7
  • A better prognosis for genetic association studies in mice Trends in Genetics Zheng, M., Dill, D., Peltz, G. 2012; 2 (28): 62–69
  • Identification of drug targets by chemogenomic and metabolomic profiling in yeast. Pharmacogenetic Genomics Wu, M., Zheng, M., Zhang, W., Suresh, S., Schlecht, U., Fitch, W. L., Dill, D. 2012
  • Next-Generation Computational Genetic Analysis: Multiple Complement Alleles Control Survival after Candida albicans Infection INFECTION AND IMMUNITY Peltz, G., Zaas, A. K., Zheng, M., Solis, N. V., Zhang, M. X., Liu, H., Hu, Y., Boxx, G. M., Phan, Q. T., Dill, D., Filler, S. G. 2011; 79 (11): 4472-4479

    Abstract

    Candida albicans is a fungal pathogen that causes severe disseminated infections that can be lethal in immunocompromised patients. Genetic factors are known to alter the initial susceptibility to and severity of C. albicans infection. We developed a next-generation computational genetic mapping program with advanced features to identify genetic factors affecting survival in a murine genetic model of hematogenous C. albicans infection. This computational tool was used to analyze the median survival data after inbred mouse strains were infected with C. albicans, which provides a useful experimental model for identification of host susceptibility factors. The computational analysis indicated that genetic variation within early classical complement pathway components (C1q, C1r, and C1s) could affect survival. Consistent with the computational results, serum C1 binding to this pathogen was strongly affected by C1rs alleles, as was survival of chromosome substitution strains. These results led to a combinatorial, conditional genetic model, involving an interaction between C5 and C1r/s alleles, which accurately predicted survival after infection. Beyond applicability to infectious disease, this information could increase our understanding of the genetic factors affecting susceptibility to autoimmune and neurodegenerative diseases.

    View details for DOI 10.1128/IAI.05666-11

    View details for Web of Science ID 000296352400018

    View details for PubMedID 21875959

  • Are Cells Asynchronous Circuits? (Invited Talk) 12th International Conference on Verification, Model Checking, and Abstract Interpretation Dill, D. L. SPRINGER-VERLAG BERLIN. 2011: 1–1
  • Next-generation computational genetic analysis: Multiple complement alleles control survival after candida albicans infection Infection and Immunity Peltz, G., Zaas, A., K., Zheng, M., Solis, N., V., Zhang, M., X., Liu, H., H., Dill, D. 2011; 11 (79): 4472–4479
  • The Role of Interleukin-1 in Wound Biology. Part II: In Vivo and Human Translational Studies ANESTHESIA AND ANALGESIA Hu, Y., Liang, D., Li, X., Liu, H., Zhang, X., Zheng, M., Dill, D., Shi, X., Qiao, Y., Yeomans, D., Carvalho, B., Angst, M. S., Clark, J. D., Peltz, G. 2010; 111 (6): 1534-1542

    Abstract

    In the accompanying paper, we demonstrate that genetic variation within Nalp1 could contribute to interstrain differences in wound chemokine production through altering the amount of interleukin (IL)-1 produced. We further investigate the role of IL-1 in incisional wound biology and its effect on wound chemokine production in vivo and whether this mechanism could be active in human subjects.A well-characterized murine model of incisional wounding was used to assess the in vivo role of IL-1 in wound biology. The amount of 7 different cytokines/chemokines produced within an experimentally induced skin incision on a mouse paw and the nociceptive response was analyzed in mice treated with an IL-1 inhibitor. We also investigated whether human IL-1β or IL-1α stimulated the production of chemokines by primary human keratinocytes in vitro, and whether there was a correlation between IL-1β and chemokine levels in 2 experimental human wound paradigms.Administration of an IL-1 receptor antagonist to mice decreased the nociceptive response to an incisional wound, and reduced the production of multiple inflammatory mediators, including keratinocyte-derived chemokine (KC) and macrophage inhibitory protein (MIP)-1α, within the wounds. IL-1α and IL-1β stimulated IL-8 and GRO-α (human homologues of murine keratinocyte-derived chemokine) production by primary human keratinocytes in vitro. IL-1β levels were highly correlated with IL-8 in human surgical wounds, and at cutaneous sites of human ultraviolet B-induced sunburn injury.IL-1 plays a major role in regulating inflammatory mediator production in wounds through a novel mechanism; by stimulating the production of multiple cytokines and chemokines, it impacts clinically important aspects of wound biology. These data suggest that administration of an IL-1 receptor antagonist within the perioperative period could decrease postsurgical wound pain.

    View details for DOI 10.1213/ANE.0b013e3181f691eb

    View details for Web of Science ID 000284973300033

    View details for PubMedID 20889944

  • The Role of Interleukin-1 in Wound Biology. Part I: Murine In Silico and In Vitro Experimental Analysis ANESTHESIA AND ANALGESIA Hu, Y., Liang, D., Li, X., Liu, H., Zhang, X., Zheng, M., Dill, D., Shi, X., Qiao, Y., Yeomans, D., Carvalho, B., Angst, M. S., Clark, J. D., Peltz, G. 2010; 111 (6): 1525-1533

    Abstract

    Wound healing is a multistep, complex process that involves the coordinated action of multiple cell types. Conflicting results have been obtained when conventional methods have been used to study wound biology. Therefore, we analyzed the wound response in a mouse genetic model.We analyzed inflammatory mediators produced within incisional wounds induced in 16 inbred mouse strains. Computational haplotype-based genetic analysis of inter-strain differences in the level of production of 2 chemokines in wounds was performed. An in vitro experimental analysis system was developed to investigate whether interleukin (IL)-1 could affect chemokine production by 2 different types of cells that are present within wounds.The level of 2 chemokines, keratinocyte-derived chemokine (KC) and macrophage inflammatory protein 1α, exhibited very large (75- and 463-fold, respectively) interstrain differences within wound tissue across this inbred strain panel. Genetic variation within Nalp1, an inflammasome component that regulates IL-1 production, correlated with the interstrain differences in KC and macrophage inhibitory protein 1α production. Consistent with the genetic correlation, IL-1β was shown to stimulate KC production by murine keratinocyte and fibroblast cell lines in vitro.Genetic variation within Nalp1 could contribute to interstrain differences in wound chemokine production by altering the amount of IL-1 produced.

    View details for DOI 10.1213/ANE.0b013e3181f5ef5a

    View details for Web of Science ID 000284973300032

    View details for PubMedID 20889942

  • MiDReG: A method of mining developmentally regulated genes using Boolean implications PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Sahoo, D., Seita, J., Bhattacharya, D., Inlay, M. A., Weissman, I. L., Plevritis, S. K., Dill, D. L. 2010; 107 (13): 5732-5737

    Abstract

    We present a method termed mining developmentally regulated genes (MiDReG) to predict genes whose expression is either activated or repressed as precursor cells differentiate. MiDReG does not require gene expression data from intermediate stages of development. MiDReG is based on the gene expression patterns between the initial and terminal stages of the differentiation pathway, coupled with "if-then" rules (Boolean implications) mined from large-scale microarray databases. MiDReG uses two gene expression-based seed conditions that mark the initial and the terminal stages of a given differentiation pathway and combines the statistically inferred Boolean implications from these seed conditions to identify the relevant genes. The method was validated by applying it to B-cell development. The algorithm predicted 62 genes that are expressed after the KIT+ progenitor cell stage and remain expressed through CD19+ and AICDA+ germinal center B cells. qRT-PCR of 14 of these genes on sorted B-cell progenitors confirmed that the expression of 10 genes is indeed stably established during B-cell differentiation. Review of the published literature of knockout mice revealed that of the predicted genes, 63.4% have defects in B-cell differentiation and function and 22% have a role in the B cell according to other experiments, and the remaining 14.6% are not characterized. Therefore, our method identified novel gene candidates for future examination of their role in B-cell development. These data demonstrate the power of MiDReG in predicting functionally important intermediate genes in a given developmental pathway that is defined by a mutually exclusive gene expression pattern.

    View details for DOI 10.1073/pnas.0913635107

    View details for Web of Science ID 000276159500010

    View details for PubMedID 20231483

  • Timing Robustness in the Budding and Fission Yeast Cell Cycles PLOS ONE Mangla, K., Dill, D. L., Horowitz, M. A. 2010; 5 (2)

    Abstract

    Robustness of biological models has emerged as an important principle in systems biology. Many past analyses of Boolean models update all pending changes in signals simultaneously (i.e., synchronously), making it impossible to consider robustness to variations in timing that result from noise and different environmental conditions. We checked previously published mathematical models of the cell cycles of budding and fission yeast for robustness to timing variations by constructing Boolean models and analyzing them using model-checking software for the property of speed independence. Surprisingly, the models are nearly, but not totally, speed-independent. In some cases, examination of timing problems discovered in the analysis exposes apparent inaccuracies in the model. Biologically justified revisions to the model eliminate the timing problems. Furthermore, in silico random mutations in the regulatory interactions of a speed-independent Boolean model are shown to be unlikely to preserve speed independence, even in models that are otherwise functional, providing evidence for selection pressure to maintain timing robustness. Multiple cell cycle models exhibit strong robustness to timing variation, apparently due to evolutionary pressure. Thus, timing robustness can be a basis for generating testable hypotheses and can focus attention on aspects of a model that may need refinement.

    View details for DOI 10.1371/journal.pone.0008906

    View details for Web of Science ID 000274209700002

    View details for PubMedID 20126540

  • The role of interleukin-1 in wound biology. part i: murine in silico and in vitro experimental analysis Anesthesia & Analgesia Hu, Y., Liang, D., Li, X., Liu, H., Zhang, X., Zheng, M., Dill, D. 2010; 6 (111): 1525–1533
  • Timing robustness in the budding and fission yeast cell cycles PLoS ONE Mangla, K., Dill, D. L., Horowitz, M. A. 2010; 2 (5): e8906
  • The role of interleukin-1 in wound biology. part ii: in vivo and human translational studies Anesthesia & nalgesia Hu, Y., Liang, D., Li, X., Liu, H., Zhang, X., Zheng, M., Dill, D. 2010; 6 (111): 1534–1542
  • Gene expression changes induced by genistein in the prostate cancer cell line lncap Open Prostate Cancer J Bhamre, S., Sahoo, D., Tibshirani, R., Dill, D., L., Brooks, J., D 2010; 3: 86–98
  • Ly6d marks the earliest stage of B-cell specification and identifies the branchpoint between B-cell and T-cell development GENES & DEVELOPMENT Inlay, M. A., Bhattacharya, D., Sahoo, D., Serwold, T., Seita, J., Karsunky, H., Plevritis, S. K., Dill, D. L., Weissman, I. L. 2009; 23 (20): 2376-2381

    Abstract

    Common lymphoid progenitors (CLPs) clonally produce both B- and T-cell lineages, but have little myeloid potential in vivo. However, some studies claim that the upstream lymphoid-primed multipotent progenitor (LMPP) is the thymic seeding population, and suggest that CLPs are primarily B-cell-restricted. To identify surface proteins that distinguish functional CLPs from B-cell progenitors, we used a new computational method of Mining Developmentally Regulated Genes (MiDReG). We identified Ly6d, which divides CLPs into two distinct populations: one that retains full in vivo lymphoid potential and produces more thymocytes at early timepoints than LMPP, and another that behaves essentially as a B-cell progenitor.

    View details for DOI 10.1101/gad.1836009

    View details for Web of Science ID 000270849700004

    View details for PubMedID 19833765

  • Temporal Changes in Gene Expression Induced by Sulforaphane in Human Prostate Cancer Cells PROSTATE Bhamre, S., Sahoo, D., Tibshirani, R., Dill, D. L., Brooks, J. D. 2009; 69 (2): 181-190

    Abstract

    Prostate cancer is thought to arise as a result of oxidative stresses and induction of antioxidant electrophile defense (phase 2) enzymes has been proposed as a prostate cancer prevention strategy. The isothiocyanate sulforaphane, derived from cruciferous vegetables like broccoli, potently induces surrogate markers of phase 2 enzyme activity in prostate cells in vitro and in vivo. To better understand the temporal effects of sulforaphane and broccoli sprouts on gene expression in prostate cells, we carried out comprehensive transcriptome analysis using cDNA microarrays.Transcripts significantly modulated by sulforaphane over time were identified using StepMiner analysis. Ingenuity Pathway Analysis (IPA) was used to identify biological pathways, networks, and functions significantly altered by sulforaphane treatment.StepMiner and IPA revealed significant changes in many transcripts associated with cell growth and cell cycle, as well as a significant number associated with cellular response to oxidative damage and stress. Comparison to an existing dataset suggested that sulforaphane blocked cell growth by inducing G2/M arrest. Cell growth assays and flow cytometry analysis confirmed that sulforaphane inhibited cell growth and induced cell cycle arrest.Our data suggest that in prostate cells sulforaphane primarily induces cellular defenses and inhibits cell growth by causing G2/M phase arrest. Furthermore, based on the striking similarities in the gene expression patterns induced across experiments in these cells, sulforaphane appears to be the primary bioactive compound present in broccoli sprouts, suggesting that broccoli sprouts can serve as a suitable source for sulforaphane in intervention trials.

    View details for DOI 10.1002/pros.20869

    View details for Web of Science ID 000262701200008

    View details for PubMedID 18973173

  • Temporal changes in gene expression induced by sulforaphane in human prostate cancer cells The Prostate Bhamre, S., Sahoo, D., Tibshirani, R., Dill, D., Brooks, J. 2009; 2 (69): 181–90
  • Ly6d marks the earliest stage of b-cell specification and identifies the branchpoint between b-cell and t-cell development Genes and Development Inlay, Matthew, A., Bhattacharya, D., Sahoo, D., Serwold, T., Seita, J., Karsunky, H., Dill, D. 2009; 20 (23): 2376–2381
  • EXE: Automatically Generating Inputs of Death 13th ACM Conference on Computer and Communications Security Cadar, C., Ganesh, V., Pawlowski, P. M., Dill, D. L., Engler, D. R. ASSOC COMPUTING MACHINERY. 2008
  • Point/Counterpoint The U. S. Should Ban Paperless Electronic Voting Machines COMMUNICATIONS OF THE ACM Dill, D. L. 2008; 51 (10): 29-30
  • Architecture and inherent robustness of a bacterial cell-cycle control system PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Shen, X., Collier, J., Dill, D., Shapiro, L., Horowitz, M., McAdams, H. H. 2008; 105 (32): 11340-11345

    Abstract

    A closed-loop control system drives progression of the coupled stalked and swarmer cell cycles of the bacterium Caulobacter crescentus in a near-mechanical step-like fashion. The cell-cycle control has a cyclical genetic circuit composed of four regulatory proteins with tight coupling to processive chromosome replication and cell division subsystems. We report a hybrid simulation of the coupled cell-cycle control system, including asymmetric cell division and responses to external starvation signals, that replicates mRNA and protein concentration patterns and is consistent with observed mutant phenotypes. An asynchronous sequential digital circuit model equivalent to the validated simulation model was created. Formal model-checking analysis of the digital circuit showed that the cell-cycle control is robust to intrinsic stochastic variations in reaction rates and nutrient supply, and that it reliably stops and restarts to accommodate nutrient starvation. Model checking also showed that mechanisms involving methylation-state changes in regulatory promoter regions during DNA replication increase the robustness of the cell-cycle control. The hybrid cell-cycle simulation implementation is inherently extensible and provides a promising approach for development of whole-cell behavioral models that can replicate the observed functionality of the cell and its responses to changing environmental conditions.

    View details for DOI 10.1073/pnas.0805258105

    View details for Web of Science ID 000258560700056

    View details for PubMedID 18685108

  • Genomic and proteomic analysis reveals a threshold level of MYC required for tumor maintenance CANCER RESEARCH Shachaf, C. M., Gentles, A. J., Elchuri, S., Sahoo, D., Soen, Y., Sharpe, O., Perez, O. D., Chang, M., Mitchel, D., Robinson, W. H., Dill, D., Nolan, G. P., Plevritis, S. K., Felsher, D. W. 2008; 68 (13): 5132-5142

    Abstract

    MYC overexpression has been implicated in the pathogenesis of most types of human cancers. MYC is likely to contribute to tumorigenesis by its effects on global gene expression. Previously, we have shown that the loss of MYC overexpression is sufficient to reverse tumorigenesis. Here, we show that there is a precise threshold level of MYC expression required for maintaining the tumor phenotype, whereupon there is a switch from a gene expression program of proliferation to a state of proliferative arrest and apoptosis. Oligonucleotide microarray analysis and quantitative PCR were used to identify changes in expression in 3,921 genes, of which 2,348 were down-regulated and 1,573 were up-regulated. Critical changes in gene expression occurred at or near the MYC threshold, including genes implicated in the regulation of the G(1)-S and G(2)-M cell cycle checkpoints and death receptor/apoptosis signaling. Using two-dimensional protein analysis followed by mass spectrometry, phospho-flow fluorescence-activated cell sorting, and antibody arrays, we also identified changes at the protein level that contributed to MYC-dependent tumor regression. Proteins involved in mRNA translation decreased below threshold levels of MYC. Thus, at the MYC threshold, there is a loss of its ability to maintain tumorigenesis, with associated shifts in gene and protein expression that reestablish cell cycle checkpoints, halt protein translation, and promote apoptosis.

    View details for DOI 10.1158/0008-5472.CAN-07-6192

    View details for Web of Science ID 000257415300024

    View details for PubMedID 18593912

  • Combined Analysis of Murine and Human Microarrays and ChIP Analysis Reveals Genes Associated with the Ability of MYC To Maintain Tumorigenesis PLOS GENETICS Wu, C., Sahoo, D., Arvanitis, C., Bradon, N., Dill, D. L., Felsher, D. W. 2008; 4 (6)

    Abstract

    The MYC oncogene has been implicated in the regulation of up to thousands of genes involved in many cellular programs including proliferation, growth, differentiation, self-renewal, and apoptosis. MYC is thought to induce cancer through an exaggerated effect on these physiologic programs. Which of these genes are responsible for the ability of MYC to initiate and/or maintain tumorigenesis is not clear. Previously, we have shown that upon brief MYC inactivation, some tumors undergo sustained regression. Here we demonstrate that upon MYC inactivation there are global permanent changes in gene expression detected by microarray analysis. By applying StepMiner analysis, we identified genes whose expression most strongly correlated with the ability of MYC to induce a neoplastic state. Notably, genes were identified that exhibited permanent changes in mRNA expression upon MYC inactivation. Importantly, permanent changes in gene expression could be shown by chromatin immunoprecipitation (ChIP) to be associated with permanent changes in the ability of MYC to bind to the promoter regions. Our list of candidate genes associated with tumor maintenance was further refined by comparing our analysis with other published results to generate a gene signature associated with MYC-induced tumorigenesis in mice. To validate the role of gene signatures associated with MYC in human tumorigenesis, we examined the expression of human homologs in 273 published human lymphoma microarray datasets in Affymetrix U133A format. One large functional group of these genes included the ribosomal structural proteins. In addition, we identified a group of genes involved in a diverse array of cellular functions including: BZW2, H2AFY, SFRS3, NAP1L1, NOLA2, UBE2D2, CCNG1, LIFR, FABP3, and EDG1. Hence, through our analysis of gene expression in murine tumor models and human lymphomas, we have identified a novel gene signature correlated with the ability of MYC to maintain tumorigenesis.

    View details for DOI 10.1371/journal.pgen.1000090

    View details for Web of Science ID 000260410300026

    View details for PubMedID 18535662

    View details for PubMedCentralID PMC2390767

  • Boolean implication networks derived from large scale, whole genome microarray datasets GENOME BIOLOGY Sahoo, D., Dill, D. L., Gentles, A. J., Tibshirani, R., Plevritis, S. K. 2008; 9 (10)

    Abstract

    We describe a method for extracting Boolean implications (if-then relationships) in very large amounts of gene expression microarray data. A meta-analysis of data from thousands of microarrays for humans, mice, and fruit flies finds millions of implication relationships between genes that would be missed by other methods. These relationships capture gender differences, tissue differences, development, and differentiation. New relationships are discovered that are preserved across all three species.

    View details for Web of Science ID 000260587300020

    View details for PubMedID 18973690

  • Boolean implication networks derived from large scale, whole genome microarray datasets Genome Biology Sahoo, D., Dill, D., L., Gentles, A., J., Tibshirani, R., Plevritis, S., K. 2008; 10 (9): R157
  • Architecture and inherent robustness of a bacterial cell-cycle control system Proceedings of the National Academy of Sciences Shen, X., Collier, J., Dill, D., L., Shapiro, L., Horowitz, M., McAdams, H., H. 2008; 32 (105): 11340–11345
  • EXE: automatically generating inputs of death. ACM Transactions on Information and System Security Cadar, C., Ganesh, V., Pawlowski, Peter, M., Dill, David, L., Engler, Dawson, R. 2008; 2 (12)
  • Combined analysis of murine and human microarrays and chip analysis reveals genes associated with the ability of myc to maintain tumorigenesis. PLoS Genetics Wu, C., H., Sahoo, D., Arvanitis, C., Bradon, N., Dill, D., L., Felsher, D., W. 2008; 6 (4)
  • Genomic and proteomic analysis reveals a threshold level of myc required for tumor maintenance Cancer Research Shachaf, C., M., Gentles, A., J., Elchuri, S., Sahoo, D., Soen, Y., Sharpe, O., Dill, D. 2008; 13 (68): 5132
  • Automatic Formal Verification of Block Cipher Implementations 8th International Conference on Formal Methods in Computer-Aided Design Smith, E. W., Dill, D. L. IEEE. 2008: 45–51
  • A retrospective on Mur phi Symposium on 25 Years of Model Checking (25MC) Dill, D. L. SPRINGER-VERLAG BERLIN. 2008: 77–88
  • Extracting binary signals from microarray time-course data NUCLEIC ACIDS RESEARCH Sahoo, D., Dill, D. L., Tibshirani, R., Plevritis, S. K. 2007; 35 (11): 3705-3712

    Abstract

    This article presents a new method for analyzing microarray time courses by identifying genes that undergo abrupt transitions in expression level, and the time at which the transitions occur. The algorithm matches the sequence of expression levels for each gene against temporal patterns having one or two transitions between two expression levels. The algorithm reports a P-value for the matching pattern of each gene, and a global false discovery rate can also be computed. After matching, genes can be sorted by the direction and time of transitions. Genes can be partitioned into sets based on the direction and time of change for further analysis, such as comparison with Gene Ontology annotations or binding site motifs. The method is evaluated on simulated and actual time-course data. On microarray data for budding yeast, it is shown that the groups of genes that change in similar ways and at similar times have significant and relevant Gene Ontology annotations.

    View details for DOI 10.1093/nar/gkm284

    View details for Web of Science ID 000247817500018

    View details for PubMedID 17517782

  • A decision procedure for bit-vectors and arrays 19th International Conference on Computer Aided Verification Ganesh, V., Dill, D. L. SPRINGER-VERLAG BERLIN. 2007: 519–531
  • A retrospective on murφ In 25 years of Model Checking, volume 4925 of Lecture Notes in Computer Science Dill, David, L. 2007: 1
  • Extracting boolean signals from microarray time course data. Nucleic Acids Research Sahoo, D., Dill, David, L., Tibshirani, R., Plevritis, Sylvia, K. 2007; 11 (35): 3705–3712
  • The Pathalyzer: A tool for analysis of signal transduction pathways Joint Annual Workshop on Systems Biology and on Regulatory Genomics Dill, D. L., Knapp, M. A., Gage, P., Talcott, C., Laderoute, K., Lincoln, P. SPRINGER-VERLAG BERLIN. 2007: 11–22
  • A refinement method for validity checking of quantified first-order formulas in hardware verification 6th International Conference on Formal Methods in Computer Aided Design Abu-Haimed, H., Dill, D. L., Berezin, S. IEEE COMPUTER SOC. 2006: 145–152
  • Multiple representations of biological processes. Transactions on Computational Systems Biology Talcott, C., Dill, David, L. 2006: 221–245
  • Multiple representations of biological processes 4th International Conference on Computational Methods in Systems Biology Talcott, C., Dill, D. L. SPRINGER-VERLAG BERLIN. 2006: 221–245
  • The pathway logic assistant Talcott, C., Dill, David, L. 2005
  • Evaluation of voting systems. Commun. ACM Vora, P., L., Adida, B., Bucholz, R., Chaum, D., Dill, D., L., Jefferson, D. 2004; 11 (47): 144
  • A partitioning methodology for BDD-based verification 5th International Conference on Formal Methods in Computer-Aided Design (FMCAD) Sahoo, D., Iyer, S., Jain, J., Stangier, C., Narayan, A., Dill, D. L., Emerson, E. A. SPRINGER-VERLAG BERLIN. 2004: 399–413
  • A practical approach to partial functions in CVC Lite. Barrett, C., Berezin, S., Shikanian, I., Chechik, M., Gurfinkel, A., Dill, David, L. 2004
  • A partitioning methodology for bdd-based verification Sahoo, D., Iyer, Subramanian, K., Jain, J., Stangier, C., Narayan, A., Dill, David, L. 2004
  • Guest editors' introduction: E-voting security. IEEE Security and Privacy Dill, David, L., Rubin, Aviel, D. 2004; 1 (2)
  • A proof-producing boolean search engine. Barrett, C., Berezin, S., Dill, David, L. 2003
  • Using formal specifications for functional validation of hardware designs IEEE DESIGN & TEST OF COMPUTERS Shimizu, K., Dill, D. L. 2002; 19 (4): 96-106
  • Efficient algorithms for approximate time separation of events SADHANA-ACADEMY PROCEEDINGS IN ENGINEERING SCIENCES Chakraborty, S., Dill, D. L., Yun, K. Y. 2002; 27: 129-162
  • Formal verification of out-of-order execution with incremental flushing FORMAL METHODS IN SYSTEM DESIGN Jones, R. B., Skakkebaek, J. U., Dill, D. L. 2002; 20 (2): 139-158
  • Counter-example based predicate discovery in predicate abstraction 4th International Conference on Formal Methods in Computer-Aided Design (FMCAD 2002) Das, S., Dill, D. L. SPRINGER-VERLAG BERLIN. 2002: 19–32
  • CVC: a Cooperating Validity Checker. Stump, A., Barrett, C., Dill, D. 2002
  • Checking Satisfiability of First-Order Formulas by Incremental Translation to SAT. Barrett, Clark, W., Dill, David, L., Stump, A. edited by Brinksma, E., Larsen, K. G. 2002
  • Using formal specifications for functional validation of hardware designs IEEE Design & Test of Computers Shimizu, K., Dill, David, L. 2002; 4 (19): 96–106
  • Deriving a simulation input generator and a coverage metric from a formal specification 39th Design Automation Conference Shimizu, K., Dill, D. L. ASSOC COMPUTING MACHINERY. 2002: 801–806
  • Deciding Presburger arithmetic by model checking and comparisons with other methods 4th International Conference on Formal Methods in Computer-Aided Design (FMCAD 2002) Ganesh, V., Berezin, S., Dill, D. L. SPRINGER-VERLAG BERLIN. 2002: 171–186
  • Parallelizing the Mur phi verifier 9th International Conference on Computer-Aided Verification (CAV 97) Stern, U., Dill, D. L. SPRINGER. 2001: 117–29
  • A simple method for extracting models from protocol code 28th Annual International Symposium on Computer Architecture Lie, D., Chou, A., Engler, D., Dill, D. L. IEEE COMPUTER SOC. 2001: 192–203
  • A decision procedure for an extensional theory of arrays 16th Annual IEEE Symposium on Logic in Computer Science Stump, A., Barrett, C. W., Dill, D. L., LEVITT, J. IEEE COMPUTER SOC. 2001: 29–37
  • Successive approximation of abstract transition relations 16th Annual IEEE Symposium on Logic in Computer Science Das, S., Dill, D. L. IEEE COMPUTER SOC. 2001: 51–58
  • Automatic checking of aggregation abstractions through state enumeration IEEE TRANSACTIONS ON COMPUTER-AIDED DESIGN OF INTEGRATED CIRCUITS AND SYSTEMS Park, S., Das, S., Dill, D. L. 2000; 19 (10): 1202-1210
  • Monitor-based formal specification of PCI 3rd International Conference on Formal Methods in Computer-Aided Design Shimizu, K., Dill, D. L., Hu, A. J. SPRINGER-VERLAG BERLIN. 2000: 335–353
  • Reliable verification using symbolic simulation with scalar values 37th Annual Design Automation Conference (DAC) Wilson, C., Dill, D. L. ASSOC COMPUTING MACHINERY. 2000: 124–129
  • Counterexample-guided choice of projections in approximate symbolic model checking IEEE/ACM International Conference on Computer Aided Design (ICCAD-2000) Govindaraju, S. G., Dill, D. L. IEEE. 2000: 115–119
  • Java model checking 15th IEEE International Conference on Automated Software Engineering (ASE 2000) Park, D. Y., Stern, U., Skakkebaek, J. U., Dill, D. L. IEEE COMPUTER SOC. 2000: 253–256
  • Symbolic simulation with approximate values 3rd International Conference on Formal Methods in Computer-Aided Design Wilson, C., Dill, D. L., Bryant, R. E. SPRINGER-VERLAG BERLIN. 2000: 470–485
  • A framework for cooperating decision procedures 17th International Conference on Automated Deduction (CADE-17) Barrett, C. W., Dill, D. L., Stump, A. SPRINGER-VERLAG BERLIN. 2000: 79–98
  • Timing analysis of asynchronous systems using time separation of events IEEE TRANSACTIONS ON COMPUTER-AIDED DESIGN OF INTEGRATED CIRCUITS AND SYSTEMS Chakraborty, S. A., Yun, K. Y., Dill, D. L. 1999; 18 (8): 1061-1076
  • Verifying systems with replicated components in Mur phi FORMAL METHODS IN SYSTEM DESIGN Ip, C. N., Dill, D. L. 1999; 14 (3): 273-310
  • Automatic synthesis of extended burst-mode circuits: Part I (specification and hazard-free implementations) IEEE TRANSACTIONS ON COMPUTER-AIDED DESIGN OF INTEGRATED CIRCUITS AND SYSTEMS Yun, K. Y., Dill, D. L. 1999; 18 (2): 101-117
  • An executable specification and verifier for relaxed memory order IEEE TRANSACTIONS ON COMPUTERS Park, S. J., Dill, D. L. 1999; 48 (2): 227-235
  • Min-max timing analysis and an application to asynchronous circuits PROCEEDINGS OF THE IEEE Chakraborty, S., Dill, D. L., Yun, K. Y. 1999; 87 (2): 332-346
  • Automatic synthesis of extended burst-mode circuits: Part II (automatic synthesis) IEEE TRANSACTIONS ON COMPUTER-AIDED DESIGN OF INTEGRATED CIRCUITS AND SYSTEMS Yun, K. Y., Dill, D. L. 1999; 18 (2): 118-132
  • Timing analysis of asynchronous systems using time separation of events. IEEE Transactions on Computer-Aided Design Chakraborty, S., Yun, Kenneth, Y., Dill, David, L. 1999; 8 (18): 1061–1076
  • Experience with predicate abstraction. Das, S., Dill, David, L., Park, S. 1999
  • Automatic synthesis of extended burst-mode circuits: Part I (specification and hazard-free implementations). IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems Yun, Kenneth, Y., Dill, David, L. 1999; 2 (18): 101–117
  • Improved approximate reachability using auxiliary state variables. Govindaraju, Shankar, G., Dill, David, L., Bergmann, Jules, P. 1999
  • Automatic synthesis of extended burst-mode circuits: Part II (specification and hazard-free implementations). IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems Yun, Kenneth, Y., Dill, David, L. 1999; 2 (18): 118–132
  • An executable specification, analyzer and verifier for RMO (relaxed memory order). IEEE Transactions on Computers Park, S., Dill, David, L. 1999; 2 (48): 227–335
  • Verifying systems with replicated components in Murφ. Formal Methods in System Design Ip, C., Norris., Dill, David, L. 1999; 3 (14): 41–75
  • BDD-based synthesis of extended burst-mode controllers IEEE TRANSACTIONS ON COMPUTER-AIDED DESIGN OF INTEGRATED CIRCUITS AND SYSTEMS Yun, K. Y., Lin, B., Dill, D. L., Devadas, S. 1998; 17 (9): 782-792
  • Verification of cache coherence protocols by aggregation of distributed transactions 8th Annual ACM Symposium on Parallel Algorithms and Architectures Park, S., Dill, D. L. SPRINGER. 1998: 355–76
  • Using magnetic disk instead of main memory in the Mur phi verifier 10th International Conference on Computer-Aided Verification (CAV 98) Stern, U., Dill, D. L. SPRINGER-VERLAG BERLIN. 1998: 172–183
  • Reducing manual abstraction in formal verification of out-of-order execution. Jones, Robert, B., Skakkebæk, Jens, U., Dill, David, L. edited by Gopalakrishnan, G., Windley, P. 1998
  • Verification of cache coherence protocols by aggregation of distributed transactions. Theory of Computing Systems Park, S., Dill, David, L. 1998; 4 (31): 355–376
  • Bdd-based synthesis of extended burst-mode controllers. IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems Yun, Kenneth, Y., Lin, B., Dill, David, L., Devadas, S. 1998; 9 (17): 782–792
  • Formally verifying data and control with weak reachability invariants. Su, Jeffrey, X., Dill, David, L., Skakkebæk, Jens, U. edited by Gopalakrishnan, G., Windley, P. 1998
  • Checking properties of safety critical specifications using efficient decision procedures. Park, David, Y.W., Skakkebæk, Jens, U., Heimdahl, Mats, P.E., Czerny, Barbara, J., Dill, David, L. 1998
  • A decision procedure for bit-vector arithmetic 35th Design Automation Conference Barrett, C. W., Dill, D. L., LEVITT, J. R. ASSOC COMPUTING MACHINERY. 1998: 522–527
  • Verification by approximate forward and backward reachability IEEE/ACM International Conference on Computer-Aided Design Govindaraju, S. G., Dill, D. L. ASSOC COMPUTING MACHINERY. 1998: 366–370
  • Static analysis to identify invariants in RSML specifications 5th International Symposium on Formal Techniques in Real-Time and Fault-Tolerant Systems (FTRTFT 98) Park, D. Y., Skakkebaek, J. U., Dill, D. L. SPRINGER-VERLAG BERLIN. 1998: 133–142
  • Format verification of out-of-order execution using incremental flushing 10th International Conference on Computer-Aided Verification (CAV 98) Skakkebaek, J. U., Jones, R. B., Dill, D. L. SPRINGER-VERLAG BERLIN. 1998: 98–109
  • Practical timing analysis of asynchronous circuits using time separation of events IEEE Custom Integrated Circuits Conference Chakraborty, S., Yun, K. Y., Dill, D. L. IEEE. 1998: 455–458
  • Approximate reachability with BDDs using overlapping projections 35th Design Automation Conference Govindaraju, S. G., Dill, D. L., Hu, A. J., Horowitz, M. A. ASSOC COMPUTING MACHINERY. 1998: 451–456
  • What's between simulation and formal verification? (Extended abstract) 35th Design Automation Conference Dill, D. L. ASSOC COMPUTING MACHINERY. 1998: 328–329
  • Validation with guided search of the state space 35th Design Automation Conference Yang, C. H., Dill, D. L. ASSOC COMPUTING MACHINERY. 1998: 599–604
  • Timing analysis for extended burst-mode circuits 3rd International Symposium on Advanced Research in Asynchronous Circuits and Systems Chakraborty, S., Dill, D. L., Yun, K. Y., Chang, K. Y. I E E E, COMPUTER SOC PRESS. 1997: 101–111
  • Approximate algorithms for time separation of events 1997 IEEE/ACM International Conference on Computer-Aided Design (ICCAD 97) Chakraborty, S., Dill, D. L. I E E E, COMPUTER SOC PRESS. 1997: 190–194
  • More accurate polynomial-time min-max timing simulation 3rd International Symposium on Advanced Research in Asynchronous Circuits and Systems Chakraborty, S., Dill, D. L. I E E E, COMPUTER SOC PRESS. 1997: 112–123
  • Parallelizing the Mur phi verifier 9th International Conference on Computer-Aided Verification (CAV 97) Stern, U., Dill, D. L. SPRINGER-VERLAG BERLIN. 1997: 256–267
  • Better verification through symmetry FORMAL METHODS IN SYSTEM DESIGN Ip, C. N., Dill, D. L. 1996; 9 (1-2): 41-75
  • State reduction using reversible rules 33rd Design Automation Conference Ip, C. N., Dill, D. L. ASSOC COMPUTING MACHINERY. 1996: 564–567
  • Verification of flash cache coherence protocol by aggregation of distributed actions. Park, S., Dill, David, L. 1996
  • Combining state space caching and hash compaction. In Methoden des Entwurfs und der Verifikation digitaler Systeme, 4. GI/ITG/GME Workshop Stern, U., Dill, D., L. 1996
  • Formal methods: state of the art and future directions. ACM Computing Surveys Clarke, E., M., Wing, J., M., Alur, R., Cleaveland, R., Dill, D., Emerson, A. 1996; 4 (28): 626–43
  • The murφ verification system. Dill, David, L. 1996
  • Protocol verification by aggregation of distributed transactions. Park, S., Dill, David, L. 1996
  • A new scheme for memory-efficient probabilistic verification. Stern, U., Dill, David, L. 1996
  • Automata-theoretic verification of real-time systems. Formal Methods for Real-time Computing, number 5 in Trends in Software Alur, R., Dill, David, L. edited by Heitmeyer, C., Mandrioli, D. 1996: 55–81
  • Protocol verification by aggregation of distributed actions. Park, S., Dill, David, L. 1996
  • Combining state space caching and hash compaction. Stern, U., Dill, David, L. 1996
  • Better verification through symmetry. Formal Methods in System Design Ip, C., Norris., Dill, David, L. 1996; 1–2 (9): 41–75
  • Validity checking for combinations of theories with equality 1st International Conference on Formal Methods in Computer-Aided Design (FMCAD 96) Barrett, C., Dill, D., LEVITT, J. SPRINGER-VERLAG BERLIN. 1996: 187–201
  • Self-consistency checking 1st International Conference on Formal Methods in Computer-Aided Design (FMCAD 96) Jones, R. B., Seger, C. J., Dill, D. L. SPRINGER-VERLAG BERLIN. 1996: 159–171
  • Automatic generation of invariants in processor verification 1st International Conference on Formal Methods in Computer-Aided Design (FMCAD 96) Su, J. X., Dill, D. L., Barrett, C. W. SPRINGER-VERLAG BERLIN. 1996: 377–388
  • EXACT 2-LEVEL MINIMIZATION OF HAZARD-FREE LOGIC WITH MULTIPLE-INPUT CHANGES IEEE TRANSACTIONS ON COMPUTER-AIDED DESIGN OF INTEGRATED CIRCUITS AND SYSTEMS Nowick, S. M., Dill, D. L. 1995; 14 (8): 986-997
  • Architecture validation for processors 22nd Annual International Symposium on Computer Architecture Ho, R. C., Yang, C. H., Horowitz, M. A., Dill, D. L. ASSOC COMPUTING MACHINERY. 1995: 404–413
  • A high-performance asynchronous SCSI controller International Conference on Computer Design - VLSI in Computers and Processors (ICCD 95) Yun, K. Y., Dill, D. L. IEEE COMPUTER SOC. 1995: 44–49
  • Exact two-level minimization of hazard-free logic with multiple-input changes. IEEE Transactions on Computer-Aided Design of Integrated Circuits Nowick, S., M., Dill, D., L. 1995; 8 (14): 986–997
  • A high-performance asynchronous SCSI controller. Yun, Kenneth, Y., Dill, David, L. 1995
  • A theory of timed automata. Theoretical Computer Science Alur, R., Dill, D., L. 1995; 126: 183–235
  • Efficient validity checking for processor verification 1995 IEEE/ACM International Conference on Computer-Aided Design Jones, R. B., Dill, D. L., Burch, J. R. I E E E, COMPUTER SOC PRESS. 1995: 2–6
  • Verification of real-time systems by successive over and under approximation 7th Conference on Computer Aided Verification (CAV 95) Dill, D. L., WONGTOI, H. SPRINGER-VERLAG BERLIN. 1995: 409–422
  • Improved probabilistic verification by hash compaction IFIP WG 10.5 Advanced Research Working Conference on Correct Hardware Design and Verification Methods (CHARME 95) Stern, U., Dill, D. L. SPRINGER-VERLAG BERLIN. 1995: 206–224
  • Automatic verification of the SCI cache coherence protocol IFIP WG 10.5 Advanced Research Working Conference on Correct Hardware Design and Verification Methods (CHARME 95) Stern, U., Dill, D. L. SPRINGER-VERLAG BERLIN. 1995: 21–34
  • A THEORY OF TIMED AUTOMATA THEORETICAL COMPUTER SCIENCE Alur, R., Dill, D. L. 1994; 126 (2): 183-235
  • SYMBOLIC MODEL CHECKING FOR SEQUENTIAL-CIRCUIT VERIFICATION IEEE TRANSACTIONS ON COMPUTER-AIDED DESIGN OF INTEGRATED CIRCUITS AND SYSTEMS Burch, J. R., Clarke, E. M., Long, D. E., McMillan, K. L., Dill, D. L. 1994; 13 (4): 401-424
  • SELF-TIMED LOGIC USING CURRENT-SENSING COMPLETION DETECTION (CSCD) JOURNAL OF VLSI SIGNAL PROCESSING Dean, M. E., Dill, D. L., Horowitz, M. 1994; 7 (1-2): 7-16
  • NEW TECHNIQUES FOR EFFICIENT VERIFICATION WITH IMPLICITLY CONJOINED BDDS 31st Design Automation Conference Hu, A. J., York, G., Dill, D. L. ASSOC COMPUTING MACHINERY. 1994: 276–282
  • PERFORMANCE-DRIVEN SYNTHESIS OF ASYNCHRONOUS CONTROLLERS 1994 IEEE/ACM International Conference on Computer-Aided Design Yun, K. Y., Lin, B., Dill, D. L., Devadas, S. IEEE COMPUTER SOC. 1994: 550–557
  • Conference on Computer-Aided Veri cation, of Lecture Notes in Computer Science edited by Dill, D. L. 1994
  • Performance-driven synthesis of asynchronous controllers. Yun, K., Y., Lin, B., Dill, D, L., Devadas, S. 1994
  • Symbolic model checking for sequential circuit verification. IEEE Transactions on Computer-Aided Design of Integrated Circuits Burch, Jerry, R., Clarke, Edmund, M., Long, David, E., McMillan, Kenneth, L., Dill, David, L. 1994; 4 (13): 401–424
  • Automatic verification of pipelined microprocessor control. Burch, Jerry, R., Dill, David, L. edited by Dill, D. L. 1994
  • Self-timed logic using current sensing completion detection (CSCD). Journal of VLSI Signal Processing Dean, M., Dill, David, L., Horowitz, M. 1994; 1–2 (7): 7–16
  • THE DESIGN OF A HIGH-PERFORMANCE CACHE CONTROLLER - A CASE-STUDY IN ASYNCHRONOUS SYNTHESIS INTEGRATION-THE VLSI JOURNAL Nowick, S. M., Dean, M. E., Dill, D. L., Horowitz, M. 1993; 15 (3): 241-262
  • MODEL-CHECKING IN DENSE REAL-TIME INFORMATION AND COMPUTATION Alur, R., Courcoubetis, C., Dill, D. 1993; 104 (1): 2-34
  • UNIFYING SYNCHRONOUS ASYNCHRONOUS STATE MACHINE SYNTHESIS 1993 IEEE/ACM International Conference on Computer-Aided Design Yun, K. Y., Dill, D. L. I E E E, COMPUTER SOC PRESS. 1993: 255–260
  • EFFICIENT VERIFICATION OF SYMMETRICAL CONCURRENT SYSTEMS 1993 IEEE INTERNATIONAL CONFERENCE ON COMPUTER DESIGN : VLSI IN COMPUTERS AND PROCESSES Ip, C. N., Dill, D. L. I E E E, COMPUTER SOC PRESS. 1993: 230–234
  • AUTOMATIC TECHNOLOGY MAPPING FOR GENERALIZED FUNDAMENTAL-MODE ASYNCHRONOUS DESIGNS 30TH DESIGN AUTOMATION CONF Siegel, P., Demicheli, G., Dill, D. ASSOC COMPUTING MACHINERY. 1993: 61–67
  • Efficient verification of bdds using implicitly conjoined invariants. Hu, Alan, J., Dill, David, L. 1993
  • Higher-level specification and verification with BDDs. Hu, Alan, J., Dill, David, L., Drexler, Andreas, J., Yang, C., Han 1993
  • Automatic technology mapping for generalized fundamental-mode asynchronous designs Siegel, P., Micheli, G. D., Dill, D. 1993
  • Automatic technology mapping for generalized fundamental-mode asynchronous designs. Technical Report CSL-TR-93-580, Stanford University Computer Systems Laboratory Siegel, P., Micheli, G. D., Dill, D. 1993
  • Model-Checking for Real-Time Systems. Information and Computation Alur, R., Courcoubetis, C., Dill, D. 1993; 1 (104): 2–34
  • Practical generalizations of asynchronous state machines. Yun, Kenneth, Y., Dill, David, L., Nowick, Steven, M. 1993
  • The design of a high-performance cache controller: a case study in asynchronous synthesis. Integration: the VLSI Journal Nowick, S., M., Dean, M., E., Dill, D., L., Horowitz, M. 1993; 3 (15): 241–262
  • Reducing BDD size by exploiting functional dependencies. Hu, Alan, J., Dill, David, L. 1993
  • Efficient verification of symmetric concurrent systems. Ip, C. N., Dill, David, L. 1993
  • BETTER VERIFICATION THROUGH SYMMETRY IFIP WG10.2 International Conference on Computer Hardware Description Languages and their Applications (CHDL 93) Ip, C. N., Dill, D. L. ELSEVIER SCIENCE BV. 1993: 97–111
  • MODELING HIERARCHICAL COMBINATIONAL-CIRCUITS 1993 IEEE/ACM International Conference on Computer-Aided Design Burch, J. R., Dill, D., Wolf, E., Demicheli, G. I E E E, COMPUTER SOC PRESS. 1993: 612–617
  • FORMAL SPECIFICATION OF ABSTRACT MEMORY MODELS Symposium on Research on Integrated Systems Dill, D. L., Park, S., Nowatzyk, A. G. M I T PRESS. 1993: 38–52
  • SYMBOLIC MODEL CHECKING - 1020 STATES AND BEYOND 5TH SYMP ON LOGIC IN COMPUTER SCIENCE Burch, J. R., Clarke, E. M., McMillan, K. L., Dill, D. L., Hwang, L. J. ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS. 1992: 142–70
  • CHECKING FOR LANGUAGE INCLUSION USING SIMULATION PREORDERS LECTURE NOTES IN COMPUTER SCIENCE Dill, D. L., Hu, A. J., WONGTOI, H. 1992; 575: 255-265
  • ALGORITHMS FOR INTERFACE TIMING VERIFICATION 1992 IEEE INTERNATIONAL CONF ON COMPUTER DESIGN : VLSI IN COMPUTERS & PROCESSORS ( ICCD 92 ) McMillan, K. L., Dill, D. L. I E E E, COMPUTER SOC PRESS. 1992: 48–51
  • MINIMIZATION OF TIMED TRANSITION-SYSTEMS 3RD INTERNATIONAL CONF ON CONCURRENCY THEORY Alur, R., Courcoubetis, C., Halbwachs, N., Dill, D., WONGTOI, H. SPRINGER-VERLAG BERLIN. 1992: 340–354
  • CHECKING FOR LANGUAGE INCLUSION USING SIMULATION PREORDERS 3RD INTERNATIONAL WORKSHOP ON COMPUTER AIDED VERIFICATION ( CAV 91 ) Dill, D. L., Hu, A. J., WONGTOI, H. SPRINGER-VERLAG BERLIN. 1992: 255–265
  • PRACTICAL ASYNCHRONOUS CONTROLLER-DESIGN 1992 IEEE INTERNATIONAL CONF ON COMPUTER DESIGN : VLSI IN COMPUTERS & PROCESSORS ( ICCD 92 ) Nowick, S. M., Yun, K. Y., Dill, D. L. I E E E, COMPUTER SOC PRESS. 1992: 341–345
  • SYNTHESIS OF 3D ASYNCHRONOUS STATE MACHINES 1992 IEEE INTERNATIONAL CONF ON COMPUTER DESIGN : VLSI IN COMPUTERS & PROCESSORS ( ICCD 92 ) Yun, K. Y., Dill, D. L., Nowick, S. M. I E E E, COMPUTER SOC PRESS. 1992: 346–350
  • AN IMPLEMENTATION OF 3 ALGORITHMS FOR TIMING VERIFICATION BASED ON AUTOMATA EMPTINESS CONF ON REAL-TIME SYSTEMS SYMP Alur, R., Courcoubetis, C., Dill, D., Halbwachs, N., WONGTOI, H. I E E E, COMPUTER SOC PRESS. 1992: 157–166
  • Synthesis of 3D asynchronous state machines. Yun, Kenneth, Y., Dill, David, L. 1992
  • Protocol verification as a hardware design aid. Dill, David, L., Drexler, Andreas, J., Hu, Alan, J., Yang, C., Han 1992
  • Practical asynchronous controller design. Nowick, Steven, M., Yun, K., Dill, David, L. 1992
  • Algorithms for interface timing verification. McMillan, K., Dill, David, L. 1992
  • Specification and automatic verification of self-timed queues Formal Methods in Systems Design Dill, David, L., Nowick, Steven, M., Sproull, Robert, F. 1992; 1 (1): 29–62
  • Automatic synthesis of 3D asynchronous state machines. Yun, Kenneth, Y., Dill, David, L. 1992
  • The theory of timed automata. In Real-Time: Theory in Practice, volume 600 of Lecture Notes in Computer Science Alur, R., Dill, David, L. REX Workshop, Mook, The Netherlands. 1992: 45–73
  • Practical generalizations of asynchronous state machines. Technical Report CSL-TR-92-544, Computer Systems Laboratory, Stanford University Yun, Kenneth, Y., Dill, David, L., Nowick, Steven, M. 1992
  • Formal Verification of Cache Systems using Refinement Relations. Formal Methods in Systems Design Loewenstein, P., Dill, D. 1992; 4 (1): 355–383
  • Verification with real-time COSPAN. Courcoubetis, C., Dill, D., Chatzaki, M., Tzounakis, P. 1992
  • An Implementation of Three Algorithms for Timing Veri cation Based on Automata Emptiness. Alur, R., Courcoubetis, C., Dill, D., Halbwachs, N., Wong-Toi, H. 1992
  • Verifying automata specifications of probabilistic real-time systems. In Real-Time: Theory in Practice, volume 600 of Lecture Notes in Computer Science Alur, R., Courcoubetis, C., Dill, David, L. REX Workshop, Mook, The Netherlands. 1992: 28–44
  • Symbolic model checking: 1020 states and beyond. Information and Computation Burch, J., R., Clarke, E., M., McMillan, K., L., Dill, D., L., Hwang, L., J. 1992; 2 (98): 142–170
  • THE THEORY OF TIMED AUTOMATA REX WORKSHOP ON REAL-TIME : THEORY IN PRACTICE Alur, R., Dill, D. SPRINGER VERLAG. 1992: 45–73
  • VERIFYING AUTOMATA SPECIFICATIONS OF PROBABILISTIC REAL-TIME SYSTEMS REX WORKSHOP ON REAL-TIME : THEORY IN PRACTICE Alur, R., Courcoubetis, C., Dill, D. SPRINGER VERLAG. 1992: 28–44
  • MINIMIZATION OF TIMED TRANSITION-SYSTEMS LECTURE NOTES IN COMPUTER SCIENCE Alur, R., Courcoubetis, C., Halbwachs, N., Dill, D., WONGTOI, H. 1992; 630: 340-354
  • MODEL-CHECKING FOR PROBABILISTIC REAL-TIME SYSTEMS LECTURE NOTES IN COMPUTER SCIENCE Alur, R., Courcoubetis, C., Dill, D. 1991; 510: 115-126
  • MODEL-CHECKING FOR PROBABILISTIC REAL-TIME SYSTEMS 18TH INTERNATIONAL COLLOQUIUM ON AUTOMATA, LANGUAGES AND PROGRAMMING ( ICALP 91 ) Alur, R., Courcoubetis, C., Dill, D. SPRINGER-VERLAG BERLIN. 1991: 115–126
  • SYNTHESIS OF ASYNCHRONOUS STATE MACHINES USING A LOCAL CLOCK INTERNATIONAL CONF ON COMPUTER DESIGN : VLSI IN COMPUTERS AND PROCESSORS Nowick, S. M., Dill, D. L. I E E E, COMPUTER SOC PRESS. 1991: 192–197
  • Synthesis of asynchronous state machines using a local clock. Nowick, Steven, M., Dill, David, L. 1991
  • Efficient self-timing with level-encoded two-phase dual rail (LEDR). Dean, Mark, E., Williams, Ted, E., Dill, David, L. 1991
  • Automatic synthesis of locally-clocked asynchronous state machines. Nowick, Steven, M., Dill, David, L. 1991
  • SELF-TIMED LOGIC USING CURRENT-SENSING COMPLETION DETECTION (CSCD) INTERNATIONAL CONF ON COMPUTER DESIGN : VLSI IN COMPUTERS AND PROCESSORS Dean, M. E., Dill, D. L., Horowitz, M. I E E E, COMPUTER SOC PRESS. 1991: 187–191
  • SYNTHESIZING PROCESSES AND SCHEDULERS FROM TEMPORAL SPECIFICATIONS 2ND INTERNATIONAL CONF ON COMPUTER-AIDED VERIFICATION ( CAV 90 ) WONGTOI, H., Dill, D. L. SPRINGER. 1991: 272–281
  • COMPLETE TRACE STRUCTURES WORKSHOP ON HARDWARE SPECIFICATION, VERIFICATION AND SYNTHESIS : MATHEMATICAL ASPECTS Dill, D. L. SPRINGER-VERLAG BERLIN. 1990: 224–243
  • TIMING ASSUMPTIONS AND VERIFICATION OF FINITE-STATE CONCURRENT SYSTEMS LECTURE NOTES IN COMPUTER SCIENCE Dill, D. L. 1990; 407: 197-212
  • COMPLETE TRACE STRUCTURES LECTURE NOTES IN COMPUTER SCIENCE Dill, D. L. 1990; 408: 224-243
  • AUTOMATA FOR MODELING REAL-TIME SYSTEMS 17TH INTERNATIONAL COLLOQUIUM ON AUTOMATA, LANGUAGES AND PROGRAMMING ( ICALP 90 ) Alur, R., Dill, D. SPRINGER-VERLAG. 1990: 322–335
  • Symbolic model checking: 10 states and beyond. Burch, J., R., Clarke, E., M., McMillan, K., L., Dill, D., L., Hwang, J. 1990
  • Sequential circuit verification using symbolic model-checking. Burch, J., R., Clarke, E., M., Dill, D., L., McMillan, K., L. 1990
  • Specification and automatic verification of self-timed queues Formal Veri cation of Hardware Design Dill, D. L., Nowick, S. M., Sproull, R. F. edited by Yoeli, M. IEEE Computer Society Press. 1990: 225–248
  • Model-checking for real-time systems. Alur, R., Courcoubetis, C., Dill, D. 1990
  • Automatic verification of sequential circuits using temporal logic Formal Verification of Hardware Design. Browne, M. C., Clarke, E. M., Dill, D. L., Mishra, B. edited by Yoeli, M. IEEE Computer Society Press. 1990: 166–175
  • Automatic verification Synchronization Design for Digital Systems Nowick, S. M., Dill, D. L. edited by Meng, T. H. Kluwer Academic Publishers. 1990: 147–172
  • Automatic verification of asynchronous circuits using temporal logic. Formal Verification of Hardware Design, Reprint of a paper in IEE proceedings, Pt. E. Dill, David, L., Clarke, Edmund, M. edited by Yoeli, M. IEEE Computer Society Press. 1990: 176–183
  • AUTOMATA FOR MODELING REAL-TIME SYSTEMS LECTURE NOTES IN COMPUTER SCIENCE Alur, R., Dill, D. 1990; 443: 322-335
  • TIMING ASSUMPTIONS AND VERIFICATION OF FINITE-STATE CONCURRENT SYSTEMS INTERNATIONAL WORKSHOP ON AUTOMATIC VERIFICATION METHODS FOR FINITE STATE SYSTEMS Dill, D. L. SPRINGER-VERLAG BERLIN. 1990: 197–212
  • Complete trace structures In Hardware Speci cation, Veri cation and Synthesis: Mathematical Aspects, volume 408 of Lecture Notes in Computer Science Dill, D. L. 1989: 224–243
  • PRACTICALITY OF STATE-MACHINE VERIFICATION OF SPEED-INDEPENDENT CIRCUITS 1989 IEEE INTERNATIONAL CONF ON COMPUTER-AIDED DESIGN : A CONF FOR THE EE CAD PROFESSIONAL ( ICCAD-89 ) Nowick, S. M., Dill, D. L. I E E E, COMPUTER SOC PRESS. 1989: 266–269
  • AUTOMATIC VERIFICATION OF SPEED-INDEPENDENT CIRCUITS WITH PETRI NET SPECIFICATIONS 1989 IEEE INTERNATIONAL CONF ON COMPUTER DESIGN : VLSI IN COMPUTERS AND PROCESSORS Dill, D. L., Nowick, S. M., SPROULL, R. F. I E E E. 1989: 212–216
  • Practicality of state-machine verification of speed-independent circuits. Nowick, Steven, M., Dill, David, L. 1989
  • Automatic verification of speed-independent circuits with Petri net specifications. Dill, David, L., Nowick, Steven, M., Sproull, Robert, F. 1989
  • Trace Theory for Automatic Hierarchical Veri cation of Speed-independent Circuits edited by Dill, D. L. MIT Press. 1989
  • Specification and automatic verification of self-timed queues. Technical Report CSL-TR-89-387, Computer Systems Laboratory, Stanford University, This was reprinted in the IEEE tutorial: Formal Verification of Hardware Design, by Michael Yoeli Dill, David, L., Nowick, Steven, M., Sproull, Robert, F. 1989
  • Trace theory for automatic hierarchical verification of speed-independent circuits. Dill, David, L. 1988
  • AUTOMATIC VERIFICATION OF SEQUENTIAL-CIRCUITS USING TEMPORAL LOGIC IEEE TRANSACTIONS ON COMPUTERS Browne, M. C., Clarke, E. M., Dill, D. L., Mishra, B. 1986; 35 (12): 1035-1044
  • AUTOMATIC VERIFICATION OF ASYNCHRONOUS CIRCUITS USING TEMPORAL LOGIC IEE PROCEEDINGS-E COMPUTERS AND DIGITAL TECHNIQUES Dill, D. L., Clarke, E. M. 1986; 133 (5): 276-282
  • Automatic verification of sequential circuits using temporal logic. IEEE Transactions on Computers, This was reprinted in the IEEE tutorial: Formal Veri cation of Hardware Design, by Michael Yoeli Browne, Michael, C., Clarke, Edmund, M., Dill, David, L., Mishra, B. 1986; 12 (C-35): 1035–1044
  • Automatic circuit verification using temporal logic: Two new examples. Browne, Michael, C., Clarke, Edmund, M., Dill, David, L. 1986
  • Automatic verification of asynchronous circuits using temporal logic Dill, David, L., Clark, Edmund, M. 1986
  • Automatic verification of asynchronous circuits using temporal logic. Technical Report CMU-CS-85-125, Department of Computer Science, Carnegie-Mellon University Dill, David, L., Clarke, Edmund, M. 1985
  • Automatic verification of sequential circuits using temporal logic. Browne, Michael, C., Clarke, Edmund, M., Dill, David, L., Mishra, B. 1985
  • Checking the correctness of sequential circuits. Browne, Michael, C., Clarke, Edmund, M., Dill, David, L. 1985
  • Automatic verification of asynchronous circuits using temporal logic. Dill, David, L., Clarke, Edmund, M. 1985
  • Automatic verification of sequential circuits using temporal logic. Technical Report CMU-CS-85-100, Department of Computer Science, Carnegie-Mellon University Browne, Michael, C., Clarke, Edmund, M., Dill, David, L., Mishra, B. 1984