Alan Moses

faculty_img Academic Title: Professor

Campus: St. George

CSB Appointment: Full

Primary Undergraduate Department:
Cell & Systems Biology

Graduate Programs:
Cell & Systems Biology

Titles and Honors:
Canada Research Chair in Computational Biology

Academic or Administrative Appointments:
Director of the Collaborative Graduate Program in Genome Biology and Bioinformatics

Education:
Ph.D. University of California, Berkeley 2005
B.A. Columbia University 2000

Mailing Address
Department of Cell & Systems Biology
University of Toronto
25 Harbord St.
Toronto, ON M5S 3G5
Canada
Contact Information
Office phone: 416-946-3980
Office: RW 515B
Lab: RW 504
Lab phone: 416-978-5563
Email: alan.moses@utoronto.ca
URL: http://www.moseslab.csb.utoronto.ca/
Research Areas
Bioinformatics & Computational Biology
Comparative Genomics
Evolutionary Biology
Microbiology
Molecular Biology
Proteomics
Systems Biology
Research

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.

Publications

2019

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Variational Infinite Heterogeneous Mixture Model for Semi-supervised Clustering of Heart Enhancers..Mehdi TF, Singh G, Mitchell JA, Moses AM. Bioinformatics 2019 Feb 07; ():
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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. G3 2019 02 07; 9(2):561-570
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2018

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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. BMC Syst Biol 2018 Jul 03; 12(1):75
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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. Elife 2018 04 05; 7():
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NoLogo: a new statistical model highlights the diversity and suggests new classes of Crm1-dependent nuclear export signals..Liku ME, Legere EA, Moses AM. BMC Bioinformatics 2018 02 27; 19(1):65
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2017

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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. PLoS Genet. 2017 04; 13(4):e1006735
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Selection maintains signaling function of a highly diverged intrinsically disordered region..Zarin T, Tsai CN, Nguyen Ba AN, Moses AM. Proc. Natl. Acad. Sci. U.S.A. 2017 02 21; 114(8):E1450-E1459
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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. G3 2017 03 10; 7(3):911-921
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Introduction of Premature Stop Codons as an Evolutionary Strategy To Rescue Signaling Network Function..Kompella PS, Moses AM, Peisajovich SG. ACS Synth Biol 2017 03 17; 6(3):446-454
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2016

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An Unsupervised kNN Method to Systematically Detect Changes in Protein Localization in High-Throughput Microscopy Images..Lu AX, Moses AM. PLoS ONE 2016; 11(7):e0158712
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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. Plant J. 2016 11; 88(3):490-504
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Decreased Transcription Factor Binding Levels Nearby Primate Pseudogenes Suggest Regulatory Degeneration..Douglas GM, Wilson MD, Moses AM. Mol. Biol. Evol. 2016 06; 33(6):1478-85
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2015

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Short linear motifs - ex nihilo evolution of protein regulation..Davey NE, Cyert MS, Moses AM. Cell Commun. Signal 2015 Nov 21; 13():43
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Computational learning on specificity-determining residue-nucleotide interactions..Wong KC, Li Y, Peng C, Moses AM, Zhang Z. Nucleic Acids Res. 2015 Dec 02; 43(21):10180-9
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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. G3 2015 Apr 15; 5(6):1223-32
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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. Genome Biol Evol 2015 Jun 04; 7(6):1815-26
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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. Cell 2015 Jun 04; 161(6):1413-24
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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. PLoS Biol. 2015 May; 13(5):e1002146
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Local statistics allow quantification of cell-to-cell variability from high-throughput microscope images..Handfield LF, Strome B, Chong YT, Moses AM. Bioinformatics 2015 Mar 15; 31(6):940-7
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2014

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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. PLoS Comput. Biol. 2014 Dec; 10(12):e1003977
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Turnover of protein phosphorylation evolving under stabilizing selection.Landry CR, Freschi L, Zarin T, Moses AM. Front Genet 2014;5:245
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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. Dev. Cell 2014 May 12; 29(3):360-72
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Insights into molecular evolution from yeast genomics.Zarin T, Moses AM. Yeast 2014 Jul;31(7):233-41
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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. Mol. Biol. Evol. 2014 Apr;31(4):872-88
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2013

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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. Nat. Genet. 2013 Aug;45(8):891-8
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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. PLoS Comput. Biol. 2013;9(6):e1003085
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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. BMC Genomics 2013;14:69
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2012

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Towards a theoretical understanding of false positives in DNA motif finding.Zia A, Moses AM. BMC Bioinformatics 2012;13:151
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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. Sci Signal 2012 Mar;5(215):rs1
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Predicting kinase substrates using conservation of local motif density.Lai AC, Nguyen Ba AN, Moses AM. Bioinformatics 2012 Apr;28(7):962-9
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2011

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Ranking insertion, deletion and nonsense mutations based on their effect on genetic information.Zia A, Moses AM. BMC Bioinformatics 2011;12:299
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In vitro evolution goes deep.Moses AM, Davidson AR. Proc. Natl. Acad. Sci. U.S.A. 2011 May;108(20):8071-2
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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. Genome Biol. 2011;12(4):R39
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Modeling the evolution of a classic genetic switch.Josephides C, Moses AM. BMC Syst Biol 2011;5:24
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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. PLoS ONE 2011;6(1):e15934
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Polymorphism, divergence, and the role of recombination in Saccharomyces cerevisiae genome evolution.Cutter AD, Moses AM. Mol. Biol. Evol. 2011 May;28(5):1745-54
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2010

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Moving from transcriptional to phospho-evolution: generalizing regulatory evolution?.Moses AM, Landry CR. Trends Genet. 2010 Nov;26(11):462-7
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Evolution of characterized phosphorylation sites in budding yeast.Nguyen Ba AN, Moses AM. Mol. Biol. Evol. 2010 Sep;27(9):2027-37
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Evidence for widespread adaptive evolution of gene expression in budding yeast.Fraser HB, Moses AM, Schadt EE. Proc. Natl. Acad. Sci. U.S.A. 2010 Feb;107(7):2977-82
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2009

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Statistical tests for natural selection on regulatory regions based on the strength of transcription factor binding sites.Moses AM. BMC Evol. Biol. 2009;9:286
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NLStradamus: a simple Hidden Markov Model for nuclear localization signal prediction.Nguyen Ba AN, Pogoutse A, Provart N, Moses AM. BMC Bioinformatics 2009;10:202
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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. Nature 2009 Mar;458(7236):337-41
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Inferring selection on amino acid preference in protein domains.Moses AM, Durbin R. Mol. Biol. Evol. 2009 Mar;26(3):527-36
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2008

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Androgen receptor and Kennedy disease/spinal bulbar muscular atrophy.Monks DA, Rao P, Mo K, Johansen JA, Lewis G, Kemp MQ. Horm Behav 2008 May;53(5):729-40
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Sexual dimorphism and androgen regulation of satellite cell population in differentiating rat levator ani muscle.Niel L, Willemsen KR, Volante SN, Monks DA. Dev Neurobiol 2008 Jan;68(1):115-22
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2007

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Determining physical constraints in transcriptional initiation complexes using DNA sequence analysis.Shultzaberger RK, Chiang DY, Moses AM, Eisen MB. PLoS ONE 2007;2(11):e1199
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Overexpression of wild-type androgen receptor in muscle recapitulates polyglutamine disease.Monks DA, Johansen JA, Mo K, Rao P, Eagleson B, Yu Z, Lieberman AP, Breedlove SM, Jordan CL. Proc. Natl. Acad. Sci. U.S.A. 2007 Nov;104(46):18259-64
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Regulatory evolution in proteins by turnover and lineage-specific changes of cyclin-dependent kinase consensus sites.Moses AM, Liku ME, Li JJ, Durbin R. Proc. Natl. Acad. Sci. U.S.A. 2007 Nov;104(45):17713-8
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Clustering of phosphorylation site recognition motifs can be exploited to predict the targets of cyclin-dependent kinase.Moses AM, Hériché JK, Durbin R. Genome Biol. 2007;8(2):R23
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2006

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Widespread discordance of gene trees with species tree in Drosophila: evidence for incomplete lineage sorting.Pollard DA, Iyer VN, Moses AM, Eisen MB. PLoS Genet. 2006 Oct;2(10):e173
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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. Nature 2006 Nov;444(7118):499-502
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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. PLoS Comput. Biol. 2006 Oct;2(10):e130
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Detecting the limits of regulatory element conservation and divergence estimation using pairwise and multiple alignments.Pollard DA, Moses AM, Iyer VN, Eisen MB. BMC Bioinformatics 2006;7:376
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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. Genome Biol. 2006;7(8):R68
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2004

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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. Genome Biol. 2004;5(12):R98
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Conservation and evolution of cis-regulatory systems in ascomycete fungi.Gasch AP, Moses AM, Chiang DY, Fraser HB, Berardini M, Eisen MB. PLoS Biol. 2004 Dec;2(12):e398
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Androgen receptor immunoreactivity in skeletal muscle: enrichment at the neuromuscular junction.Monks DA, O'Bryant EL, Jordan CL. J. Comp. Neurol. 2004 May;473(1):59-72
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2003

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Position specific variation in the rate of evolution in transcription factor binding sites.Moses AM, Chiang DY, Kellis M, Lander ES, Eisen MB. BMC Evol. Biol. 2003 Aug;3:19
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Phylogenetically and spatially conserved word pairs associated with gene-expression changes in yeasts.Chiang DY, Moses AM, Kellis M, Lander ES, Eisen MB. Genome Biol. 2003;4(7):R43
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