Alan Moses

faculty_img Academic Title: Associate 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 Willcocks St.
Toronto, ON M5S 3B2
Canada

 

Contact Information
Office phone: 416-946-3980
Office: ESC 4073
Lab: ESC 4075
Lab phone: 416-978-5563
Email: alan.moses@utoronto.ca
URL: http://labs.csb.utoronto.ca/moses/

 

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

2014

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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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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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