Dr. Ma'ayan is a Professor in the Department of Pharmacology and Systems Therapeutics, Principal Investigator of the BD2K-LINCS Data Coordination and Integration Center and Principal Investigator of the Mount Sinai Knowledge Management Center for Illuminating the Druggable Genome.
The Ma'ayan Laboratory applies computational and mathematical methods to study the complexity of regulatory networks in mammalian cells. His research team applies graph-theory algorithms, machine-learning techniques and dynamical modeling to study how intracellular regulatory systems function as networks to control cellular processes such as differentiation, de-differentiation, apoptosis and proliferation. The Ma'ayan Laboratory develops software systems to help experimental biologists form novel hypotheses from high-throughput data, and develop theories about the structure and function of regulatory networks in mammalian systems.
In the News:
Bioinformatics, Biostatistics, Cancer, Computational Biology, Drug Design and Discovery, Gene Expressions, Gene Regulation, Kidney, Mathematical Modeling of Biomedical Systems, Mathematical and Computational Biology, Proteomics, Stem Cells, Systems Biology, Systems Pharmacology, Theoretical Biology, Transcription Factors
Biophysics and Systems Pharmacology [BSP], Design Technology and Entrepreneurship [DTE], Genetics and Genomic Sciences [GGS]
BSc, Fairleigh Dickinson University
MS, Fairleigh Dickinson University
PhD, Mount Sinai School of Medicine
Postdoctoral Fellowship, Mount Sinai School of Medicine
Irma T. Hirschl Career Scientist Award
Dr. Harold and Golden Lamport Research Award
Mount Sinai School of Medicine
Doctoral Dissertation Award in the Graduate School of Biological Sciences
Mount Sinai School of Medicine
Graduate School of Biological Sciences Award for Research Achievement
Mount Sinai School of Medicine
Systems Biology, Systems Pharmacology, Biomedical Big Data, Bioinformatics, Computational Biology, Data-Mining, Software Engineering, Network Analysis
Instructor: Alexander Lachmann, PhD
Postdoctoral Fellow: Nicolas Fernandez, PhD
PhD Student: Zichen Wang, BS
Bioinformaticians and Software/Database Developers: Anders Dohlman, BA; Troy Goff, BS; Gregory Gundersen, MA; Simon Koplev, MS; Maxim Kuleshov, MS; Caroline Dias Monteiro, BS
Graduate Research Fellows: Katie Lin, BS; Colette Malyack, BS
Undergraduate Research Fellows: Esther Chen, Daniel Clarke, Axel Feldmann, Kevin Sani
Visiting High School Student: Jennifer Lin
Summary of Research Studies:
Advances in high-throughput experimental molecular biology are allowing us to elucidate the molecular mechanisms of mammalian cell regulation with ever-increasing detail. However, the potential gains from these advances are often not fully realized since high-throughput techniques often produce more data than our current ability to adequately organize, model and visualize. A particular challenge is encountered when attempting to integrate several high-dimensional datasets from multiple types of high- and low-throughput experimental techniques applied to study mammalian cells.
For the purpose of organizing, visualizing, analyzing and modeling data from such sources we develop computational approaches which can assist experimental systems-biologists to form rational hypotheses for further experimentation. We analyze high-dimensional data collected for projects integrating results from multiple layers of regulation (genomics, transcriptomics and proteomics). In addition to our research efforts, we also develop software so that our methodologies can reach and impact the Big Data biomedical research community. Below are some of the software tools we have developed:
1) Enrichr is a gene set enrichment analysis tool that includes one of the largest collections of annotated gene sets: over 80,000 gene sets organized into over 70 gene set libraries. Enrichr provides visualization of enrichment results as bar graphs, tables, canvases and networks. Enrichment is computed by three different methods and users can save and share their lists and results with a single click. An article describing the initial version of the software was published in BMC Bioinformatics. PMID: 23586463 and PMID: 27141961
3) L1000CDS2 and Drug Pair Seeker (DPS) are two tools that use the Connectivity Map gene expression datasets, including the new version that utilizes the L1000 technology, to predict single and pairs of drugs that can either mimic or reverse gene expression given signatures of differentially expressed genes. Both tools use novel algorithms developed by the Ma’ayan Laboratory to prioritize drugs and small molecules. A detailed description of Drug Pair Seeker and its application to kidney disease can be found in publication in the journal JSAN. PMID: 23559582. L100CDS2 is a new tool that has not been published yet.
4) ChIP-X Enrichment Analysis (ChEA) database contains manually extracted datasets of transcription-factor/target-gene interactions from over 100 experiments such as ChIP-chip, ChIP-seq, ChIP-PET applied to mammalian cells. We use the database to analyze mRNA expression data where we perform gene-list enrichment analysis as the prior biological knowledge gene-list library. The system is delivered as web-based interactive software. With this software users can input lists of mammalian genes for which the program computes over-representation of transcription factor targets from the ChEA database. An article describing the system has been published in the journal Bioinformatics. PMID: 20709693
5) Kinase Enrichment Analysis (KEA) is a web-based tool with an underlying database providing users with the ability to link lists of mammalian proteins/genes with the kinases that phosphorylate them. The system draws from several available kinase–substrate databases to compute kinase enrichment probability based on the distribution of kinase–substrate proportions in the background kinase–substrate database compared with kinases found to be associated with an input list of genes/proteins. An article describing the system has been published in the journal Bioinformatics. PMID: 19176546
6) Expression2Kinases (X2K) is a software tool that integrates and upgrades the functionality of ChEA, Genes2Networks, KEA and Lists2Networks into one platform and computational pipeline. Given a list of differentially expressed genes, the software identified upstream transcription factors using the software and database ChEA; X2K then connects the top identified transcription factors with Genes2Networks using databases of known protein-protein interactions; the resultant subnetwork is then entered into KEA for kinase enrichment analysis. X2K also includes all the functions for enrichment analysis available within Lists2Networks. An article describing the system has been published in the journal Bioinformatics. PMID: 22080467
We apply these and other computational methods for the analysis of data from a variety of projects with our collaborators. The results from our analyses produce concrete suggestions and predictions for further functional experiments. The predictions are tested by our collaborators and our analyses methods are delivered as software tools and databases for the systems biology research community.
For more information, please visit the Ma'ayan Laboratory website.
Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan Q, Wang Z, Koplev S, Jenkins SL, Jagodnik KM, Lachmann A, McDermott M, Gundersen GW, Ma'ayan A. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Research 2016 May; nar/gkw377.
Wang Z, Clark NR, Ma'ayan A. Drug induced adverse events prediction with the LINCS L1000 data. Bioinformatics 2016 April; bioinformatics/btw168.
Gundersen GW, Jones MR, Rouillard AD, Kou Y, Monteiro CD, Feldmann AS, Hu KS, Ma'ayan A. GEO2Enrichr: browser extension and server app to extract gene sets from GEO and analyze them for biological functions. Bioinformatics (Oxford, England) 2015 Sep; 31(18): 3060-3062.
Wang Z, Clark NR, Ma'ayan A. Dynamics of the discovery process of protein-protein interactions from low content studies. BMC Systems Biology 2015 Jun; 9(1).
Ma'ayan A, Duan Q. A blueprint of cell identity. Nature Biotechnology 2014 Oct; 32(10): 1007-1008.
Xu H, Ang YS, Sevilla A, Lemischka IR, Ma'ayan A. Construction and validation of a regulatory network for pluripotency and self-renewal of mouse embryonic stem cells. PLoS Computational Biology 2014 Aug; 10(8): e1003777.
Duan Q, Flynn C, Niepel M, Hafner M, Muhlich JL, Fernandez NF, Rouillard AD, Tan CM, Chen EY, Golub TR, Sorger PK, Subramanian A, Ma'ayan A. LINCS Canvas Browser: interactive web app to query, browse and interrogate LINCS L1000 gene expression signatures. Nucleic Acids Research 2014 Jul; 42(W1): W449-460.
Clark NR, Hu KS, Feldmann AS, Kou Y, Chen EY, Duan Q, Ma'ayan A. The characteristic direction: a geometrical approach to identify differentially expressed genes. BMC Bioinformatics 2014 Mar; 15(79).
Tan CM, Chen EY, Dannenfelser R, Clark NR, Ma'ayan A. Network2Canvas: network visualization on a canvas with enrichment analysis. Bioinformatics 2013 Aug; 29(15): 1872-1878.
Duan Q, Kou Y, Clark NR, Gordonov S, Ma'ayan A. Metasignatures identify two major subtypes of breast cancer. CPT: Pharmacometrics and Systems Pharmacology 2013 Mar; 2(e35).
Clark NR, Dannenfelser R, Tan CM, Komosinski ME, Ma'ayan A. Sets2Networks: network inference from repeated observations of sets. BMC Systems Biology 2012 Jul; 6(89).
Jin Y, Ratnam K, Chuang PY, Fan Y, Zhong Y, Dai Y, Mazloom AR, Chen EY, D'Agati V, Xiong H, Ross MJ, Chen N, Ma'ayan A, He JC. A systems approach identifies HIPK2 as a key regulator of kidney fibrosis. Nature Medicine 2012 Mar; 18(4): 580-588.
Chen EY, Xu H, Gordonov S, Lim MP, Perkins MH, Ma'ayan A. Expression2Kinases: mRNA profiling linked to multiple upstream regulatory layers. Bioinformatics 2012 Jan; 28(1): 105-111.
Mazloom AR, Dannenfelser R, Clark NR, Grigoryan AV, Linder KM, Cardozo TJ, Bond JC, Boran AD, Iyengar R, Malovannaya A, Lanz RB, Ma'ayan A. Recovering protein-protein and domain-domain interactions from aggregation of IP-MS proteomics of coregulator complexes. PLoS Computational Biology 2011 Dec; 7(12): e1002319.
Lachmann A, Xu H, Krishnan J, Berger SI, Mazloom AR, Ma'ayan A. ChEA: Transcription factor regulation inferred from integrating genome-wide ChIP-X experiments. Bioinformatics 2010 Oct; 26(19): 2438-2444.
MacArthur BD, Sanchez-Garcia RJ, Ma'ayan A. Microdynamics and criticality of adaptive regulatory networks. Physical Review Letters 2010 Apr; 104(16): 168701.
MacArthur BD, Lachmann A, Lemischka IR, Ma'ayan A. GATE: software for the analysis and visualization of high-dimensional time series expression data. Bioinformatics 2010 Jan; 26(1): 143-144.
Lachmann A, Ma'ayan A. KEA: kinase enrichment analysis. Bioinformatics 2009 Mar; 25(5): 684-686.
Ma'ayan A. Insights into the organization of biochemical regulatory networks using graph theory analyses. Journal of Biological Chemistry 2009 Feb; 284(9): 5451-5455.
Ma'ayan A, Cecchi GA, Wagner J, Rao AR, Iyengar R, Stolovitzky G. Ordered cyclic motifs contribute to dynamic stability in biological and engineered networks. Proc Natl Acad Sci U S A 2008 Dec; 105(49): 19235-19240.
Ma'ayan A, Jenkins SL, Neves S, Hasseldine A, Grace E, Dubin-Thaler B, Eungdamrong NJ, Weng G, Ram PT, Rice JJ, Kershenbaum A, Stolovitzky GA, Blitzer RD, Iyengar R. Formation of regulatory patterns during signal propagation in a Mammalian cellular network. Science 2005 Aug; 309(5737): 1078-1083.
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