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Mount Sinai’s Knowledge Management Center for Illuminating the Druggable Genome

  • Avi Ma’ayan, Ph.D.
    Co-Principal Investigator
    Professor, Department of Pharmacological Sciences
    Director, Mount Sinai Center for Bioinformatics at Icahn School of Medicine at Mount Sinai

  • Joel Dudley, Ph.D.
    Co-Principal Investigator
    Assistant Professor, Department of Genetics and Genomic Sciences
    Director of Biomedical Informatics, Icahn School of Medicine at Mount Sinai

Overview

KMC administrated via Icahn School of Medicine at Mount Sinai spans the two laboratories of two co-PI’s at ISMMS: Dr. Avi Ma’ayan and Dr. Joel Dudley.

The work in Dr. Ma’ayan’s group focuses on collecting and integrating numerous gene expression data and functionality data in a manner that could then be disseminated efficiently by researchers to enrich the development of hypothesis via the application of graph-theory algorithm and machine learning techniques in the development of different visualization tools.

Dr. Dudley’s work applies some of these biomedical informatics approaches to the analysis of molecular and clinical data, thus identifying novel therapeutic and diagnostic approaches for addressing human disease.

The Mount Sinai KMC-IDG collects, processes, and maintains attributes about the druggable targets for all proposed families: protein kinases, G-protein coupled receptors, nuclear receptors and ion channels. Our emphasis is to focus on those genes/proteins that are under-studied and collect unbiased genome-wide profiling genomic datasets. In addition, the Mount Sinai's KMC-IDG collects, processes and maintain data tables and attributes for all other genes/proteins, drugs/small-molecules and other perturbagens, pheontypes/diseases/side-effects, and clinical as well as genomics datasets from cohorts of patients. This enables us to identify links between and across genes/proteins networks, drugs/small-molecules and other perturbagens networks, pheontypes/diseases/side-effects networks, and clusters of individual patients with similar profiles. For this, we develop and apply clustering and classification algorithms as well as workflows to make predictions about the potential applicability of targeting the under-studied proteins for various translational applications in personalized medicine.

Search for genes or proteins and their functional terms extracted & organized from over a hundred publicly available resources.

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Publications

Gundersen, Gregory W; Jagodnik, Kathleen M; Woodland, Holly; Fernandez, Nicholas F; Sani, Kevin; Dohlman, Anders B; Ung, Peter Man-Un; Monteiro, Caroline D; Schlessinger, Avner; Ma’ayan, Avi, GEN3VA: aggregation and analysis of gene expression signatures from related studies., BMC Bioinformatics 17(1):461 (2016), PubMed Abstract: https://www.ncbi.nlm.nih.gov/pubmed/27846806

Wang, Zichen ; Monteiro, Caroline D; et al […] Ma’ayan, Avi, Extraction and analysis of signatures from the Gene Expression Omnibus by the crowd., Nature Communications 7:12846 (2016), PubMed Abstract: https://www.ncbi.nlm.nih.gov/pubmed/27667448

Wang, Zichen; Ma’ayan, Avi, An open RNA-Seq data analysis pipeline tutorial with an example of reprocessing data from a recent Zika virus study., F1000Research 5:1574 (2016), PubMed Abstract: https://www.ncbi.nlm.nih.gov/pubmed/27583132

Rouillard, Andrew D; Gundersen, Gregory W; Fernandez, Nicolas F; Wang, Zichen; Monteiro, Caroline D; McDermott, Michael G; Ma'ayan, Avi, The harmonizome: a collection of processed datasets gathered to serve and mine knowledge about genes and proteins., Database (Oxford) pii: baw100 (2016), PubMed Abstract: http://www.ncbi.nlm.nih.gov
/pubmed/27374120

Kuleshov, Maxim V; Jones, Matthew R; Rouillard, Andrew D; Fernandez, Nicolas F; Duan, Qiaonan; Wang, Zichen; Koplev, Simon, Jenkins, Sherry L; Jagodnik, Kathleen M; Lachmann, Alexander, McDermott, Michael G, Monteiro, Caroline D, Gundersen, Gregory W, Ma'ayan, Avi, Enrichr: a comprehensive gene set enrichment analysis web server 2016 update., Nucleic Acids Research pii: gkw377 (2016), PubMed Abstract: http://www.ncbi.nlm.nih.gov/pubmed/27141961

Wang, Zichen; Clark, Neil R; Ma'ayan, Avi, Drug induced adverse events prediction with the LINCS L1000 data., Bioinformatics doi:10.1093/bioinformatics/btw168 (2016), PubMed Abstract: http://www.ncbi.nlm.nih.gov/pubmed/27153606

Kong, Doo-Sik; Kim, Jinkuk; Lee, In-Hee; Kim, Sung Tae; Seol, Ho Jun; Lee, Jung-Il; Park, Woong-Yang; Ryu, Gyuha; Wang, Zichen; Ma’ayan, Avi; Nam, Do-Hyun, Integrative radiogenomic analysis for multicentric radiophenotype in glioblastoma., Oncotarget doi: 10.18632/oncotarget.7115 (2016), PubMed Abstract: http://www.ncbi.nlm.nih.gov/pubmed/26863628

Kidd, Brian A; Hoffman, Gabriel; Zimmerman, Noah; Li, Li; Morgan, Joseph W; Glowe, Patricia K; Botwin, Gregory J; Parekh, Samir; Babic, Nikolina; Doust, Matthew W; Stock, Gregory B; Schadt, Eric E; Dudley, Joel T, Evaluation of direct-to-consumer low-volume lab tests in healthy adults., J Clin Invest pii: 86318 (2016), PubMed Abstract: http://www.ncbi.nlm.nih.gov/pubmed/27018593

Shameer, Khader; Badgeley, Marcus A; Miotto, Riccardo; Glicksberg, Benjamin S; Morgan, Joseph W; Dudley, Joel T, Translational bioinformatics in the era of real-time biomedical, health care and wellness data streams., Brief Bioinform pii: bbv118 (2016), PubMed Abstract: http://www.ncbi.nlm.nih.gov/pubmed/26876889

Khan, Jalal A; Mendelson, Avital; Kunisaki, Yuya; Birbrair, Alexander; Kou, Yan; Arnal-Estapé, Anna; Pinho, Sandra; Ciero, Paul; Nakahara, Fumio; Ma'ayan, Avi; Bergman, Aviv; Merad, Miriam; Frenette, Paul S, Fetal liver hematopoietic stem cell niches associate with portal vessels., Science 351 (6269): 176-80 (2016), PubMed Abstract: http://www.ncbi.nlm.nih.gov/pubmed/26634440

Kidd, Brian A; Wroblewska, Aleksandra; Boland, Mary R; Agudo, Judith; Merad, Miriam; Tatonetti, Nicholas P; Brown, Brian D; Dudley, Joel T, Mapping the effects of drugs on the immune system., Nat Biotechnol 34 (1): 47-54 (2016), PubMed Abstract: http://www.ncbi.nlm.nih.gov/pubmed/26619012

Gundersen, Gregory W; Jones, Matthew R; Rouillard, Andrew D; Kou, Yan; Monteiro, Caroline D; Feldmann, Axel S; Hu, Kevin S; Ma'ayan, Avi, GEO2Enrichr: browser extension and server app to extract gene sets from GEO and analyze them for biological functions., Bioinformatics 31 (18): 3060-2 (2015), PubMed Abstract: http://www.ncbi.nlm.nih.gov/pubmed/25971742

Sennett, Rachel; Wang, Zichen; Rezza, Amélie; Grisanti, Laura; Roitershtein, Nataly; Sicchio, Cristina; Mok, Ka Wai; Heitman, Nicholas J; Clavel, Carlos; Ma'ayan, Avi; Rendl, Michael, An Integrated Transcriptome Atlas of Embryonic Hair Follicle Progenitors, Their Niche, and the Developing Skin., Dev Cell 34 (5): 577-91 (2015), PubMed Abstract: http://www.ncbi.nlm.nih.gov/pubmed/26256211

Li, Li; Cheng, Wei-Yi; Glicksberg, Benjamin S; Gottesman, Omri; Tamler, Ronald; Chen, Rong; Bottinger, Erwin P; Dudley, Joel T, Identification of type 2 diabetes subgroups through topological analysis of patient similarity., Sci Transl Med 7 (311):(2015), PubMed Abstract: http://www.ncbi.nlm.nih.gov/pubmed/26511511

Shameer, Khader; Readheaed, Ben; Dudley, Joel T, Computational and experimental advances in drug repositioning for accelerated therapeutic stratification., Curr Top Med Chem 15(1):5-20 (2015), PubMed Abstract: http://www.ncbi.nlm.nih.gov/pubmed/25579574

Stockton Jr, Steven D; Gomes, Ivone; Liu, Tong; Moraje, Chandrakala; Hipólito, Lucia; Jones, Matthew R; Ma'ayan, Avi; Morón, Jose A; Li, Hong; Devi, Lakshmi A, Morphine Regulated Synaptic Networks Revealed by Integrated Proteomics and Network Analysis., Mol Cell Proteomics 14 (10): 2564-76 (2015), PubMed Abstract: http://www.ncbi.nlm.nih.gov/pubmed/26149443

Kidd, Brian A; Readhead, Ben P; Eden, Caroline; Parekh, Samir; Dudley, Joel T, Integrative network modeling approaches to personalized cancer medicine., Per Med 12(3):245-257 (2015), PubMed Abstract: http://www.ncbi.nlm.nih.gov/pubmed/27019658

Xu, Ke; Schadt, Eric E; Pollard, Katherine S; Roussos, Panos; Dudley, Joel T, Genomic and network patterns of schizophrenia genetic variation in human evolutionary accelerated regions., Mol Biol Evol 32 (5): 1148-60 (2015), PubMed Abstract: http://www.ncbi.nlm.nih.gov/pubmed/25681384

Björkegren, Johan L M; Kovacic, Jason C; Dudley, Joel T; Schadt, Eric E, Genome-wide significant loci: how important are they? Systems genetics to understand heritability of coronary artery disease and other common complex disorders., J Am Coll Cardiol 65 (8): 830-45 (2015), PubMed Abstract: http://www.ncbi.nlm.nih.gov/pubmed/25720628

Baida, Gleb; Bhalla, Pankaj; Kirsanov, Kirill; Lesovaya, Ekaterina; Yakubovskaya, Marianna; Yuen, Kit; Guo, Shuchi; Lavker, Robert M; Readhead, Ben; Dudley, Joel T; Budunova, Irina, REDD1 functions at the crossroads between the therapeutic and adverse effects of topical glucocorticoids., EMBO Mol Med 7 (1): 42-58 (2015), PubMed Abstract: http://www.ncbi.nlm.nih.gov/pubmed/25504525

Rouillard, Andrew D; Wang, Zichen; Ma'ayan, Avi, Reprint of ''Abstraction for data integration: Fusing mammalian molecular, cellular and phenotype big datasets for better knowledge extraction''., Comput Biol Chem 59 Pt B: 123-38 (2015), PubMed Abstract: http://www.ncbi.nlm.nih.gov/pubmed/26550826

Wang, Zichen; Clark, Neil R; Ma'ayan, Avi, Dynamics of the discovery process of protein-protein interactions from low content studies., BMC Syst Biol 9: 26 (2015), PubMed Abstract: http://www.ncbi.nlm.nih.gov/pubmed/26048415

Ma'ayan, Avi; Duan, Qiaonan, A blueprint of cell identity., Nat Biotechnol 32 (10): 1007-8 (2014), PubMed Abstract: http://www.ncbi.nlm.nih.gov/pubmed/25299921

Duan, Qiaonan; Wang, Zichen; Fernandez, Nicolas F; Rouillard, Andrew D; Tan, Christopher M; Benes, Cyril H; Ma'ayan, Avi, Drug/Cell-line Browser: interactive canvas visualization of cancer drug/cell-line viability assay datasets., Bioinformatics 30 (22): 3289-90 (2014), PubMed Abstract: http://www.ncbi.nlm.nih.gov/pubmed/25100688

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