Alan M. Moses
Professor
Campus
St. George (downtown)
CSB Appointment
Full
Research Areas
Bioinformatics / Computational Biology, Evolutionary Biology, Genetics / Genomics, Microbiology, Molecular Biology, Proteomics, Systems Biology
Education
Ph.D. University of California, Berkeley 2005;B.A. Columbia University 2000
Titles and Honors
Canada Research Chair in Computational Biology
Primary Undergraduate Department
Cell & Systems Biology
Graduate Programs
Cell & Systems Biology
Academic or Administrative Appointments
Director of the Collaborative Graduate Program in Genome Biology and Bioinformatics
Research Description
Consider the incredible diversity of cells and tissues in our own bodies: an information transmitting nerve cell and a bacteria-hunting white blood cell look and act nothing alike, yet they are specified by the same genome. This feat – phenotypic diversity without genetic diversity – is accomplished by genes that turn on and off other genes in a so-called ‘regulatory network’. We seek to understand how are these regulatory networks are encoded in genome sequences. How is information in the genome converted into regulatory interactions between proteins? One of the important components of this ‘regulatory code’ has been discovered: ‘regulatory motifs’ in the sequences of DNA, RNA and proteins. One of the major aims of our research is to develop computational and statistical tools to identify these motifs. Just as differential gene activity can explain cellular and physiological diversity within a single organism (nerve cell vs. white blood cell with same genes), it has also been proposed as explanation for physiological and morphological differences between closely related organisms (chimpanzee vs. human with very similar genes). We seek to understand how regulatory networks are sculpted by evolution. Can genetic changes in regulatory interactions explain evolutionary changes in function and form? We focus on the evolution of regulatory motifs because, by mediating the regulatory interactions, they specify the connections in regulatory networks. Our goal is to translate the evolutionary differences in regulatory motifs to quantitative differences in regulatory networks, and ultimately, to their impact on organismal fitness.
Contact Information
Office Phone: 416-946-3980
Office: RW516A
Lab: RW504
Lab Phone: 416-978-5563
Email
Mailing Address
Department of Cell & Systems Biology
University of Toronto
25 Harbord St.
Toronto, ON M5S 3G5
Canada
Recent News
Publications
2023
Systematic identification of conditionally folded intrinsically disordered regions by AlphaFold2
Alderson TR, Pritišanac I, Kolarić Đ, Moses AM, Forman-Kay JD
2023, Proceedings of the National Academy of Sciences, 10.1073/pnas.2304302120
2019
Variational Infinite Heterogeneous Mixture Model for Semi-supervised Clustering of Heart Enhancers.
Mehdi TF, Singh G, Mitchell JA, Moses AM
2019, Bioinformatics (Oxford, England), 30753279
A Noisy Analog-to-Digital Converter Connects Cytosolic Calcium Bursts to Transcription Factor Nuclear Localization Pulses in Yeast.
Hsu IS, Strome B, Plotnikov S, Moses AM
2019, G3, 9, 561-570, 30573469
2018
Short linear motifs in intrinsically disordered regions modulate HOG signaling capacity.
Strome B, Hsu IS, Li Cheong Man M, Zarin T, Nguyen Ba A, Moses AM
2018, BMC systems biology, 12, 75, 29970070
Integrating images from multiple microscopy screens reveals diverse patterns of change in the subcellular localization of proteins.
Lu AX, Chong YT, Hsu IS, Strome B, Handfield LF, Kraus O, Andrews BJ, Moses AM
2018, eLife, 7, 29620521
NoLogo: a new statistical model highlights the diversity and suggests new classes of Crm1-dependent nuclear export signals.
Liku ME, Legere EA, Moses AM
2018, BMC bioinformatics, 19, 65, 29482494
2017
Parallel reorganization of protein function in the spindle checkpoint pathway through evolutionary paths in the fitness landscape that appear neutral in laboratory experiments.
Nguyen Ba AN, Strome B, Osman S, Legere EA, Zarin T, Moses AM
2017, PLoS genetics, 13, e1006735, 28410373
Functional Analysis of Kinases and Transcription Factors in Using an Integrated Overexpression Library.
Youn JY, Friesen H, Nguyen Ba AN, Liang W, Messier V, Cox MJ, Moses AM, Andrews B
2017, G3, 7, 911-921, 28122947
Selection maintains signaling function of a highly diverged intrinsically disordered region.
Zarin T, Tsai CN, Nguyen Ba AN, Moses AM
2017, Proceedings of the National Academy of Sciences of the United States of America, 114, E1450-E1459, 28167781
2016
Introduction of Premature Stop Codons as an Evolutionary Strategy To Rescue Signaling Network Function.
Kompella PS, Moses AM, Peisajovich SG
2017, ACS synthetic biology, 6, 446-454, 27935292
New BAR tools for mining expression data and exploring Cis-elements in Arabidopsis thaliana.
Austin RS, Hiu S, Waese J, Ierullo M, Pasha A, Wang TT, Fan J, Foong C, Breit R, Desveaux D, Moses A, Provart NJ
2016, The Plant journal : for cell and molecular biology, 88, 490-504, 27401965
An Unsupervised kNN Method to Systematically Detect Changes in Protein Localization in High-Throughput Microscopy Images.
Lu AX, Moses AM
2016, PloS one, 11, e0158712, 27442431
Decreased Transcription Factor Binding Levels Nearby Primate Pseudogenes Suggest Regulatory Degeneration.
Douglas GM, Wilson MD, Moses AM
2016, Molecular biology and evolution, 33, 1478-85, 26882985
2015
Short linear motifs – ex nihilo evolution of protein regulation.
Davey NE, Cyert MS, Moses AM
2015, Cell communication and signaling, 13, 43, 26589632
Computational learning on specificity-determining residue-nucleotide interactions.
Wong KC, Li Y, Peng C, Moses AM, Zhang Z
2015, Nucleic acids research, 43, 10180-9, 26527718
Yeast Proteome Dynamics from Single Cell Imaging and Automated Analysis.
Chong YT, Koh JL, Friesen H, Duffy SK, Duffy K, Cox MJ, Moses A, Moffat J, Boone C, Andrews BJ
2015, Cell, 161, 1413-24, 26046442
Polymorphism Analysis Reveals Reduced Negative Selection and Elevated Rate of Insertions and Deletions in Intrinsically Disordered Protein Regions.
Khan T, Douglas GM, Patel P, Nguyen Ba AN, Moses AM
2015, Genome biology and evolution, 7, 1815-26, 26047845
The Structure of an NDR/LATS Kinase-Mob Complex Reveals a Novel Kinase-Coactivator System and Substrate Docking Mechanism.
Gógl G, Schneider KD, Yeh BJ, Alam N, Nguyen Ba AN, Moses AM, Hetényi C, Reményi A, Weiss EL
2015, PLoS biology, 13, e1002146, 25966461
CYCLoPs: A Comprehensive Database Constructed from Automated Analysis of Protein Abundance and Subcellular Localization Patterns in Saccharomyces cerevisiae.
Koh JL, Chong YT, Friesen H, Moses A, Boone C, Andrews BJ, Moffat J
2015, G3, 5, 1223-32, 26048563
2014
Detecting functional divergence after gene duplication through evolutionary changes in posttranslational regulatory sequences.
Nguyen Ba AN, Strome B, Hua JJ, Desmond J, Gagnon-Arsenault I, Weiss EL, Landry CR, Moses AM
2014, PLoS computational biology, 10, e1003977, 25474245
Local statistics allow quantification of cell-to-cell variability from high-throughput microscope images.
Handfield LF, Strome B, Chong YT, Moses AM
2015, Bioinformatics (Oxford, England), 31, 940-7, 25398614
Turnover of protein phosphorylation evolving under stabilizing selection
Landry CR, Freschi L, Zarin T, Moses AM
2014, Frontiers in genetics, 5, 245, 25101120
Insights into molecular evolution from yeast genomics
Zarin T, Moses AM
2014, Yeast (Chichester, England), 31, 233-41, 24760744
A mesoscale abscisic acid hormone interactome reveals a dynamic signaling landscape in Arabidopsis.
Lumba S, Toh S, Handfield LF, Swan M, Liu R, Youn JY, Cutler SR, Subramaniam R, Provart N, Moses A, Desveaux D, McCourt P
2014, Developmental cell, 29, 360-72, 24823379
A high-definition view of functional genetic variation from natural yeast genomes
Bergström A, Simpson JT, Salinas F, Barré B, Parts L, Zia A, Nguyen Ba AN, Moses AM, Louis EJ, Mustonen V, Warringer J, Durbin R, Liti G
2014, Molecular biology and evolution, 31, 872-88, 24425782
2013
An atlas of over 90,000 conserved noncoding sequences provides insight into crucifer regulatory regions
Haudry A, Platts AE, Vello E, Hoen DR, Leclercq M, Williamson RJ, Forczek E, Joly-Lopez Z, Steffen JG, Hazzouri KM, Dewar K, Stinchcombe JR, Schoen DJ, Wang X, Schmutz J, Town CD, Edger PP, Pires JC, Schumaker KS, Jarvis DE, Mandáková T, Lysak MA, van den Bergh E, Schranz ME, Harrison PM, Moses AM, Bureau TE, Wright SI, Blanchette M
2013, Nature genetics, 45, 891-8, 23817568
Unsupervised clustering of subcellular protein expression patterns in high-throughput microscopy images reveals protein complexes and functional relationships between proteins
Handfield LF, Chong YT, Simmons J, Andrews BJ, Moses AM
2013, PLoS computational biology, 9, e1003085, 23785265
High quality de novo sequencing and assembly of the Saccharomyces arboricolus genome
Liti G, Nguyen Ba AN, Blythe M, Müller CA, Bergström A, Cubillos FA, Dafhnis-Calas F, Khoshraftar S, Malla S, Mehta N, Siow CC, Warringer J, Moses AM, Louis EJ, Nieduszynski CA
2013, BMC genomics, 14, 69, 23368932
2012
Towards a theoretical understanding of false positives in DNA motif finding
Zia A, Moses AM
2012, BMC bioinformatics, 13, 151, 22738169
Proteome-wide discovery of evolutionary conserved sequences in disordered regions
Nguyen Ba AN, Yeh BJ, van Dyk D, Davidson AR, Andrews BJ, Weiss EL, Moses AM
2012, Science signaling, 5, rs1, 22416277
Predicting kinase substrates using conservation of local motif density
Lai AC, Nguyen Ba AN, Moses AM
2012, Bioinformatics (Oxford, England), 28, 962-9, 22302575
2011
Ranking insertion, deletion and nonsense mutations based on their effect on genetic information
Zia A, Moses AM
2011, BMC bioinformatics, 12, 299, 21781308
In vitro evolution goes deep
Moses AM, Davidson AR
2011, Proceedings of the National Academy of Sciences of the United States of America, 108, 8071-2, 21551096
A quantitative literature-curated gold standard for kinase-substrate pairs
Sharifpoor S, Nguyen Ba AN, Youn JY, Young JY, van Dyk D, Friesen H, Douglas AC, Kurat CF, Chong YT, Founk K, Moses AM, Andrews BJ
2011, Genome biology, 12, R39, 21492431
Modeling the evolution of a classic genetic switch
Josephides C, Moses AM
2011, BMC systems biology, 5, 24, 21294912
Whole-genome analysis reveals that active heat shock factor binding sites are mostly associated with non-heat shock genes in Drosophila melanogaster
Gonsalves SE, Moses AM, Razak Z, Robert F, Westwood JT
2011, PloS one, 6, e15934, 21264254
Polymorphism, divergence, and the role of recombination in Saccharomyces cerevisiae genome evolution
Cutter AD, Moses AM
2011, Molecular biology and evolution, 28, 1745-54, 21199893
2010
Moving from transcriptional to phospho-evolution: generalizing regulatory evolution?
Moses AM, Landry CR
2010, Trends in genetics : TIG, 26, 462-7, 20817339
Evolution of characterized phosphorylation sites in budding yeast
Nguyen Ba AN, Moses AM
2010, Molecular biology and evolution, 27, 2027-37, 20368267
Evidence for widespread adaptive evolution of gene expression in budding yeast
Fraser HB, Moses AM, Schadt EE
2010, Proceedings of the National Academy of Sciences of the United States of America, 107, 2977-82, 20133628
2009
Statistical tests for natural selection on regulatory regions based on the strength of transcription factor binding sites
Moses AM
2009, BMC evolutionary biology, 9, 286, 19995462
NLStradamus: a simple Hidden Markov Model for nuclear localization signal prediction
Nguyen Ba AN, Pogoutse A, Provart N, Moses AM
2009, BMC bioinformatics, 10, 202, 19563654
Population genomics of domestic and wild yeasts
Liti G, Carter DM, Moses AM, Warringer J, Parts L, James SA, Davey RP, Roberts IN, Burt A, Koufopanou V, Tsai IJ, Bergman CM, Bensasson D, O'Kelly MJ, van Oudenaarden A, Barton DB, Bailes E, Nguyen AN, Jones M, Quail MA, Goodhead I, Sims S, Smith F, Blomberg A, Durbin R, Louis EJ
2009, Nature, 458, 337-41, 19212322
2008
Inferring selection on amino acid preference in protein domains
Moses AM, Durbin R
2009, Molecular biology and evolution, 26, 527-36, 19095755
2007
Determining physical constraints in transcriptional initiation complexes using DNA sequence analysis
Shultzaberger RK, Chiang DY, Moses AM, Eisen MB
2007, PloS one, 2, e1199, 18030333
Regulatory evolution in proteins by turnover and lineage-specific changes of cyclin-dependent kinase consensus sites
Moses AM, Liku ME, Li JJ, Durbin R
2007, Proceedings of the National Academy of Sciences of the United States of America, 104, 17713-8, 17978194
Clustering of phosphorylation site recognition motifs can be exploited to predict the targets of cyclin-dependent kinase
Moses AM, Hériché JK, Durbin R
2007, Genome biology, 8, R23, 17316440
2006
In vivo enhancer analysis of human conserved non-coding sequences
Pennacchio LA, Ahituv N, Moses AM, Prabhakar S, Nobrega MA, Shoukry M, Minovitsky S, Dubchak I, Holt A, Lewis KD, Plajzer-Frick I, Akiyama J, De Val S, Afzal V, Black BL, Couronne O, Eisen MB, Visel A, Rubin EM
2006, Nature, 444, 499-502, 17086198
Widespread discordance of gene trees with species tree in Drosophila: evidence for incomplete lineage sorting
Pollard DA, Iyer VN, Moses AM, Eisen MB
2006, PLoS genetics, 2, e173, 17132051
Large-scale turnover of functional transcription factor binding sites in Drosophila
Moses AM, Pollard DA, Nix DA, Iyer VN, Li XY, Biggin MD, Eisen MB
2006, PLoS computational biology, 2, e130, 17040121
Detecting the limits of regulatory element conservation and divergence estimation using pairwise and multiple alignments
Pollard DA, Moses AM, Iyer VN, Eisen MB
2006, BMC bioinformatics, 7, 376, 16904011
Primate-specific evolution of an LDLR enhancer
Wang QF, Prabhakar S, Wang Q, Moses AM, Chanan S, Brown M, Eisen MB, Cheng JF, Rubin EM, Boffelli D
2006, Genome biology, 7, R68, 16884525
2004
MONKEY: identifying conserved transcription-factor binding sites in multiple alignments using a binding site-specific evolutionary model
Moses AM, Chiang DY, Pollard DA, Iyer VN, Eisen MB
2004, Genome biology, 5, R98, 15575972
Conservation and evolution of cis-regulatory systems in ascomycete fungi
Gasch AP, Moses AM, Chiang DY, Fraser HB, Berardini M, Eisen MB
2004, PLoS biology, 2, e398, 15534694
2003
Position specific variation in the rate of evolution in transcription factor binding sites
Moses AM, Chiang DY, Kellis M, Lander ES, Eisen MB
2003, BMC evolutionary biology, 3, 19, 12946282