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


  • Fellow, ACM
  • Fellow, IEEE
  • Pioneer Award, Electronic Frontier Foundation

Professional Education


  • PhD, Carnegie Mellon (1987)

Current Research and Scholarly Interests


Computational methods for understanding regulatory circuits in cell biology

2013-14 Courses


Postdoctoral Advisees


Graduate and Fellowship Programs


  • Biomedical Informatics (Phd Program)

Journal Articles


  • 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

  • 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-1? or IL-1? stimulated the production of chemokines by primary human keratinocytes in vitro, and whether there was a correlation between IL-1? 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)-1?, within the wounds. IL-1? and IL-1? stimulated IL-8 and GRO-? (human homologues of murine keratinocyte-derived chemokine) production by primary human keratinocytes in vitro. IL-1? 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 1?, 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 1? production. Consistent with the genetic correlation, IL-1? 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
  • 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

  • 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
  • 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
  • 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)
  • 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)
  • 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

  • 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
  • Multiple representations of biological processes. Transactions on Computational Systems Biology Talcott, C., Dill, David, L. 2006: 221–245
  • Evaluation of voting systems. Commun. ACM Vora, P., L., Adida, B., Bucholz, R., Chaum, D., Dill, D., L., Jefferson, D. 2004; 11 (47): 144
  • Guest editors' introduction: E-voting security. IEEE Security and Privacy Dill, David, L., Rubin, Aviel, D. 2004; 1 (2)
  • Using formal specifications for functional validation of hardware designs IEEE Design & Test of Computers Shimizu, K., Dill, David, L. 2002; 4 (19): 96–106
  • 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
  • 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
  • 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
  • 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
  • Better verification through symmetry. Formal Methods in System Design Ip, C., Norris., Dill, David, L. 1996; 1–2 (9): 41–75
  • 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
  • A theory of timed automata. Theoretical Computer Science Alur, R., Dill, D., L. 1995; 126: 183–235
  • 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
  • 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
  • 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 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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 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. 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

Books and Book Chapters


  • A retrospective on murφ In 25 years of Model Checking, volume 4925 of Lecture Notes in Computer Science Dill, David, L. 2007: 1
  • 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
  • Conference on Computer-Aided Veri cation, of Lecture Notes in Computer Science edited by Dill, D. L. 1994
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Trace Theory for Automatic Hierarchical Veri cation of Speed-independent Circuits edited by Dill, D. L. MIT Press. 1989

Conference Proceedings


  • Applying a reusable election threat model at the county level Lazarus, E. L., Dill, D. L., Epstein, J., Hall, J. L. 2011
  • The pathway logic assistant Talcott, C., Dill, David, L. 2005
  • 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
  • A proof-producing boolean search engine. Barrett, C., Berezin, S., Dill, David, L. 2003
  • 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
  • Experience with predicate abstraction. Das, S., Dill, David, L., Park, S. 1999
  • Improved approximate reachability using auxiliary state variables. Govindaraju, Shankar, G., Dill, David, L., Bergmann, Jules, P. 1999
  • 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
  • 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
  • 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
  • Verification of flash cache coherence protocol by aggregation of distributed actions. Park, S., Dill, David, L. 1996
  • 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
  • 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
  • A high-performance asynchronous SCSI controller. Yun, Kenneth, Y., Dill, David, L. 1995
  • Performance-driven synthesis of asynchronous controllers. Yun, K., Y., Lin, B., Dill, D, L., Devadas, S. 1994
  • Automatic verification of pipelined microprocessor control. Burch, Jerry, R., Dill, David, L. edited by Dill, D. L. 1994
  • Efficient verification of symmetric concurrent systems. Ip, C. N., Dill, David, L. 1993
  • 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
  • Practical generalizations of asynchronous state machines. Yun, Kenneth, Y., Dill, David, L., Nowick, Steven, M. 1993
  • Reducing BDD size by exploiting functional dependencies. Hu, Alan, J., Dill, David, L. 1993
  • 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
  • Automatic synthesis of 3D asynchronous state machines. Yun, Kenneth, Y., Dill, David, L. 1992
  • 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
  • Automatic synthesis of locally-clocked asynchronous state machines. Nowick, Steven, M., Dill, David, L. 1991
  • 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
  • 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
  • Model-checking for real-time systems. Alur, R., Courcoubetis, C., Dill, D. 1990
  • 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 verification of speed-independent circuits. Dill, David, L. 1988
  • 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 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