All Publications

  • AI-READI: rethinking AI data collection, preparation and sharing in diabetes research and beyond NATURE METABOLISM Baxter, S. L., de Sa, V. R., Ferryman, K., Jain, P., Lee, C. S., Li-Pook-Than, J., Liu, T., Owen, J. P., Patel, B., Yu, Q., Zangwill, L. M., Bahmani, A., Chute, C. G., Edberg, J. C., Hurst, S., Ishikawa, H., Lee, A. Y., McGwin, G., McWeeney, S., Nebeker, C., Owsley, C., Singer, S. J., Adib, R., Adibuzzaman, M., Alavi, A., Ashley, C., Baer, A., Benton, E., Blazes, M., Cohen, A., Cordier, B., Crist, K., Cuddy, C., Gasimova, A., Gim, N., Hong, S., Kim, T., Lin, W., Mitchell, J., Ngadisastra, C., Patronilo, V., Shaffer, J., Soundarajan, S., Zhao, K., Drolet, C., Lucero, A., Matthies, D., Pittock, H., Watkins, K., York, B., Amankwa, C. E., Bangudi, M., Haboudal, N., Hallaj, S., Heinke, A., Huang, L., Kalaw, F. P., Karsolia, A., Khazaei, H., Mohammed, M., Simpkins, K., Wang, X. 2024

    View details for DOI 10.1038/s42255-024-01165-x

    View details for Web of Science ID 001350162600001

    View details for PubMedID 39516364

    View details for PubMedCentralID 4792175

  • Achieving Inclusive Healthcare through Integrating Education and Research with AI and Personalized Curricula. medRxiv : the preprint server for health sciences Bahmani, A., Cha, K., Alavi, A., Dixit, A., Ross, A., Park, R., Goncalves, F., Ma, S., Saxman, P., Nair, R., Akhavan-Sarraf, R., Zhou, X., Wang, M., Contrepois, K., Than, J. L., Monte, E., Rodriguez, D. J., Lai, J., Babu, M., Tondar, A., Rose, S. M., Akbari, I., Zhang, X., Yegnashankaran, K., Yracheta, J., Dale, K., Miller, A. D., Edmiston, S., McGhee, E. M., Nebeker, C., Wu, J. C., Kundaje, A., Snyder, M. 2024

    Abstract

    Precision medicine promises significant health benefits but faces challenges such as the need for complex data management and analytics, interdisciplinary collaboration, and education of researchers, healthcare professionals, and participants. Addressing these needs requires the integration of computational experts, engineers, designers, and healthcare professionals to develop user-friendly systems and shared terminologies. The widespread adoption of large language models (LLMs) like GPT-4 and Claude 3 highlights the importance of making complex data accessible to non-specialists. The Stanford Data Ocean (SDO) strives to mitigate these challenges through a scalable, cloud-based platform that supports data management for various data types, advanced research, and personalized learning in precision medicine. SDO provides AI tutors and AI-powered data visualization tools to enhance educational and research outcomes and make data analysis accessible for users from diverse educational backgrounds. By extending engagement and cutting-edge research capabilities globally, SDO particularly benefits economically disadvantaged and historically marginalized communities, fostering interdisciplinary biomedical research and bridging the gap between education and practical application in the biomedical field.

    View details for DOI 10.1101/2024.07.31.24311182

    View details for PubMedID 39211867

    View details for PubMedCentralID PMC11361244

  • Values and Practices to Strengthen Genetic Research Partnerships with Indigenous Communities PROGRESS IN COMMUNITY HEALTH PARTNERSHIPS-RESEARCH EDUCATION AND ACTION Burke, W., Beans, J. A., Cho, M. K., Garrison, N. A., Hiratsuka, V., Hopkins, S., Spicer, P. G., Tsosie, K. S., Woodahl, E. L., Yracheta, J. M., Thummel, K. 2022; 16 (4): 583-592

    Abstract

    Genetic datasets lack diversity and include very few data from Indigenous populations. Research models based on equitable partnership have the potential to increase Indigenous participation and have led to successful collaborations. We report here on a meeting of participants in four Indigenous community-university partnerships pursuing research on precision medicine. The goal of the meeting was to define values and practices that strengthen opportunities for genetic research. The group accorded the highest priority to developing trusting relationships, ensuring respect for Indigenous community authority, and pursuing research that has the potential to lead to community benefit. Supporting priorities included incorporation of Indigenous expertise in research planning, transparent communication, and development of community capacity, including capacity to participate in formulating research questions, informing research methodology, and leading research projects. Participants also noted the importance of attention to social determinants of health so that genetic contributors to health are evaluated in the appropriate context.

    View details for DOI 10.1353/cpr.2022.0079

    View details for Web of Science ID 000907533300003

    View details for PubMedID 36533507

  • Longitudinal personal DNA methylome dynamics in a human with a chronic condition. Nature medicine Chen, R., Xia, L., Tu, K., Duan, M., Kukurba, K., Li-Pook-Than, J., Xie, D., Snyder, M. 2018

    Abstract

    Epigenomics regulates gene expression and is as important as genomics in precision personal health, as it is heavily influenced by environment and lifestyle. We profiled whole-genome DNA methylation and the corresponding transcriptome of peripheral blood mononuclear cells collected from a human volunteer over a period of 36 months, generating 28 methylome and 57 transcriptome datasets. We found that DNA methylomic changes are associated with infrequent glucose level alteration, whereas the transcriptome underwent dynamic changes during events such as viral infections. Most DNA meta-methylome changes occurred 80-90days before clinically detectable glucose elevation. Analysis of the deep personal methylome dataset revealed an unprecedented number of allelic differentially methylated regions that remain stable longitudinally and are preferentially associated with allele-specific gene regulation. Our results revealed that changes in different types of 'omics' data associate with different physiological aspects of this individual: DNA methylation with chronic conditions and transcriptome with acute events.

    View details for PubMedID 30397358

  • Variation and genetic control of protein abundance in humans NATURE Wu, L., Candille, S. I., Choi, Y., Xie, D., Jiang, L., Li-Pook-Than, J., Tang, H., Snyder, M. 2013; 499 (7456): 79-82

    Abstract

    Gene expression differs among individuals and populations and is thought to be a major determinant of phenotypic variation. Although variation and genetic loci responsible for RNA expression levels have been analysed extensively in human populations, our knowledge is limited regarding the differences in human protein abundance and the genetic basis for this difference. Variation in messenger RNA expression is not a perfect surrogate for protein expression because the latter is influenced by an array of post-transcriptional regulatory mechanisms, and, empirically, the correlation between protein and mRNA levels is generally modest. Here we used isobaric tag-based quantitative mass spectrometry to determine relative protein levels of 5,953 genes in lymphoblastoid cell lines from 95 diverse individuals genotyped in the HapMap Project. We found that protein levels are heritable molecular phenotypes that exhibit considerable variation between individuals, populations and sexes. Levels of specific sets of proteins involved in the same biological process covary among individuals, indicating that these processes are tightly regulated at the protein level. We identified cis-pQTLs (protein quantitative trait loci), including variants not detected by previous transcriptome studies. This study demonstrates the feasibility of high-throughput human proteome quantification that, when integrated with DNA variation and transcriptome information, adds a new dimension to the characterization of gene expression regulation.

    View details for DOI 10.1038/nature12223

    View details for Web of Science ID 000321285600037

    View details for PubMedID 23676674

  • iPOP Goes the World: Integrated Personalized Omics Profiling and the Road toward Improved Health Care. Chemistry & biology Li-Pook-Than, J., Snyder, M. 2013; 20 (5): 660-666

    Abstract

    The health of an individual depends upon their DNA as well as upon environmental factors (environome or exposome). It is expected that although the genome is the blueprint of an individual, its analysis with that of the other omes such as the DNA methylome, the transcriptome, proteome, and metabolome will further provide a dynamic assessment of the physiology and health state of an individual. This review will help to categorize the current progress of omics analyses and how omics integration can be used for medical research. We believe that integrative personal omics profiling (iPOP) is a stepping stone to a new road to personalized health care and may improve disease risk assessment, accuracy of diagnosis, disease monitoring, targeted treatments, and understanding the biological processes of disease states for their prevention.

    View details for DOI 10.1016/j.chembiol.2013.05.001

    View details for PubMedID 23706632

  • Personal Omics Profiling Reveals Dynamic Molecular and Medical Phenotypes CELL Chen, R., Mias, G. I., Li-Pook-Than, J., Jiang, L., Lam, H. Y., Chen, R., Miriami, E., Karczewski, K. J., Hariharan, M., Dewey, F. E., Cheng, Y., Clark, M. J., Im, H., Habegger, L., Balasubramanian, S., O'Huallachain, M., Dudley, J. T., Hillenmeyer, S., Haraksingh, R., Sharon, D., Euskirchen, G., Lacroute, P., Bettinger, K., Boyle, A. P., Kasowski, M., Grubert, F., Seki, S., Garcia, M., Whirl-Carrillo, M., Gallardo, M., Blasco, M. A., Greenberg, P. L., Snyder, P., Klein, T. E., Altman, R. B., Butte, A. J., Ashley, E. A., Gerstein, M., Nadeau, K. C., Tang, H., Snyder, M. 2012; 148 (6): 1293-1307

    Abstract

    Personalized medicine is expected to benefit from combining genomic information with regular monitoring of physiological states by multiple high-throughput methods. Here, we present an integrative personal omics profile (iPOP), an analysis that combines genomic, transcriptomic, proteomic, metabolomic, and autoantibody profiles from a single individual over a 14 month period. Our iPOP analysis revealed various medical risks, including type 2 diabetes. It also uncovered extensive, dynamic changes in diverse molecular components and biological pathways across healthy and diseased conditions. Extremely high-coverage genomic and transcriptomic data, which provide the basis of our iPOP, revealed extensive heteroallelic changes during healthy and diseased states and an unexpected RNA editing mechanism. This study demonstrates that longitudinal iPOP can be used to interpret healthy and diseased states by connecting genomic information with additional dynamic omics activity.

    View details for DOI 10.1016/j.cell.2012.02.009

    View details for PubMedID 22424236

  • Relationship between RNA splicing and exon editing near intron junctions in wheat mitochondria PHYSIOLOGIA PLANTARUM Li-Pook-Than, J., Carrillo, C., Niknejad, N., Calixte, S., Crosthwait, J., Bonen, L. 2007; 129 (1): 23-33

    View details for DOI 10.1111/j.1399-3054.2006.00770.x

    View details for Web of Science ID 000242865700004

  • Multiple physical forms of excised group II intron RNAs in wheat mitochondria. Nucleic acids research Li-Pook-Than, J., Bonen, L. 2006; 34 (9): 2782-90

    Abstract

    Plant mitochondrial group II introns do not all possess hallmark ribozymic features such as the bulged adenosine involved in lariat formation. To gain insight into their splicing pathways, we have examined the physical form of excised introns in germinating wheat embryos. Using RT-PCR and cRT-PCR, we observed conventional lariats consistent with a two-step transesterification pathway for introns such as nad2 intron 4, but this was not the case for the cox2 intron or nad1 intron 2. For cox2, we detected full-length linear introns, which possess non-encoded 3'terminaladenosines, as well as heterogeneous circular introns, which lack 3' nucleotide stretches. These observations are consistent with hydrolytic splicing followed by polyadenylation as well as an in vivo circularization pathway, respectively. The presence of both linear and circular species in vivo is supported by RNase H analysis. Furthermore, the nad1 intron 2, which lacks a bulged nucleotide at the branchpoint position, comprised a mixed population of precisely full-length molecules and circular ones which also include a short, discrete block of non-encoded nucleotides. The presence of these various linear and circular forms of excised intron molecules in plant mitochondria points to multiple novel group II splicing mechanisms in vivo.

    View details for DOI 10.1093/nar/gkl328

    View details for PubMedID 16717283

    View details for PubMedCentralID PMC1464410

  • Variation in mitochondrial transcript profiles of protein-coding genes during early germination and seedling development in wheat. Current genetics Li-Pook-Than, J., Carrillo, C., Bonen, L. 2004; 46 (6): 374-80

    Abstract

    We examined RNA profiles of wheat mitochondrial genes during the developmental period when seeds leave dormancy, germinate and develop into seedlings. Mitochondrial RNAs isolated from 0 h to 6 days post-imbibition were subjected to Northern analysis, using coding-specific and intron-specific probes. Stable, edited mRNAs were observed in dormant seeds and precursor RNAs were subsequently detected early in embryo germination. The respiratory chain genes (nad7, cox1, cox2, atp6) showed mRNA profiles which paralleled those of the ribosomal RNAs, whereas ribosomal protein genes (rps2, rps3, rps7) had proportionately lower steady-state mRNA levels in later stages of seedling development. The relative levels of precursors compared with the respective mRNAs shifted down during development, consistent with transcription outpacing RNA processing in the early stages but co-ordination being more effective several days after imbibition. In the case of multiply split genes containing group II introns, complex patterns of splicing intermediates were observed, suggesting a lack of strict polarity of intron removal, although splicing efficiency appears to differ among introns. Excised intron RNAs typically are relatively more abundant in embryos than seedlings. These observations are consistent with a transient imbalance of RNA-processing machinery at the onset of seed germination, which is a period of rapid mitochondrial biogenesis.

    View details for DOI 10.1007/s00294-004-0544-2

    View details for PubMedID 15538573