Research

Research in the Moses Lab

The research projects we pursue typically weave together many threads from disciplines such as evolutionary genetics, systems biology, machine learning, sequence analysis, computer vision, and more. The projects we have pursued over the years reflect the diverse interests of the graduate students and postdocs who worked in the lab. Below is a listing of the main themes that define and guide many of our research projects. For a complete picture of the work that we’ve accomplished, please visit our Publications page.

Evolution and Dynamics of Regulatory Networks

CRZ1 Pulse - Ian Hsu
Zhang & Mangelsdorf 2002
Kompella et al. 2017
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Most complex cellular processes are carried out by groups of genes working together in so-called pathways or networks. We seek to understand how these networks are encoded in genome sequences, how they create dynamic biological phenotypes, and they are created by evolution.

LATEST PAPERS:

Mehdi TF, Singh G, Mitchell JA, Moses AM. Variational Infinite Heterogeneous Mixture Model for Semi-supervised Clustering of Heart Enhancers. Bioinformatics 2019 Feb 7
[button style="btn-default btn-sm" icon="glyphicon glyphicon-share" align="left" type="link" target="true" title="Bioinformatics link" link="https://academic.oup.com/bioinformatics/advance-article/doi/10.1093/bioinformatics/btz064/5308600" linkrel="" class="publication-buttons"] [button style="btn-default btn-sm" icon="glyphicon glyphicon-download-alt" align="left" type="link" target="true" title="PDF Mirror" link="http://www.moseslab.csb.utoronto.ca/Mehdi_Moses_Bioinformatics_2019.pdf" linkrel="" class="publication-buttons"] [button style="btn-default btn-sm" icon="glyphicon glyphicon-share" align="left" type="link" target="true" title="PubMed Abstract" link="https://www.ncbi.nlm.nih.gov/pubmed/30753279" linkrel="" class="publication-buttons"] [label class="publication-types"]Article[/label]
[label class="publication-tags"]Regulatory networks[/label] [label class="publication-tags"]Transcription factors[/label] [label class="publication-tags"]Genomics[/label] [label class="publication-tags"]Machine Learning[/label]
Hsu IS, Strome B, Plotnikov S, Moses AM. A Noisy Analog-to-Digital Converter Connects Cytosolic Calcium Bursts to Transcription Factor Nuclear Localization Pulses in Yeast. G3 2019 Feb 7;9(2):561-570.
[button style="btn-default btn-sm" icon="glyphicon glyphicon-share" align="left" type="link" target="true" title="G3 link" link="http://www.g3journal.org/content/9/2/561.long" linkrel="" class="publication-buttons"] [button style="btn-default btn-sm" icon="glyphicon glyphicon-download-alt" align="left" type="link" target="true" title="PDF Mirror" link="http://www.moseslab.csb.utoronto.ca/Hsu_Moses_G3_2019.pdf" linkrel="" class="publication-buttons"] [button style="btn-default btn-sm" icon="glyphicon glyphicon-share" align="left" type="link" target="true" title="PubMed Abstract" link="https://www.ncbi.nlm.nih.gov/pubmed/30573469" linkrel="" class="publication-buttons"] [label class="publication-types"]Article[/label]
[label class="publication-tags"]Regulatory networks[/label] [label class="publication-tags"]Subcellular localization[/label] [label class="publication-tags"]Time lapse microscopy[/label] [label class="publication-tags"]Cell signaling[/label]

Microscope images are big data

Lu et al. 2016
Handfield et al. 2015
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Automated microscopy has made it possible to measuring protein abundance and subcellular localization in millions of single cells. We are developing computational tools to extract basic biology from huge collections of microscope images without have to look at each one.

LATEST PAPERS:

Lu AX, Lu AX, Schormann W, Ghassemi M, Andrews DW, Moses AM The Cells Out of Sample (COOS) dataset and benchmarks for measuring out-of-sample generalization of image classifiers Advances in Neural Information Processing Systems 32 (NeurIPS 2019)
[button style="btn-default btn-sm" icon="glyphicon glyphicon-share" align="left" type="link" target="true" title="NeurIPS link" link="https://papers.nips.cc/paper/8461-the-cells-out-of-sample-coos-dataset-and-benchmarks-for-measuring-out-of-sample-generalization-of-image-classifiers" linkrel="" class="publication-buttons"] [button style="btn-default btn-sm" icon="glyphicon glyphicon-download-alt" align="left" type="link" target="true" title="PDF Mirror" link="http://www.moseslab.csb.utoronto.ca/Lu_Moses_NeurIPS_2019.pdf" linkrel="" class="publication-buttons"] [label class="publication-types"]Book Chapter[/label]
[label class="publication-tags"]Deep Learning[/label] [label class="publication-tags"]Covariate shift[/label] [label class="publication-tags"]Image analysis[/label] [label class="publication-tags"]Subcellular localization[/label]
Lu AX, Kraus OZ, Cooper S, Moses AM. Learning unsupervised feature representations for single cell microscopy images with paired cell inpainting. PLoS Comput Biol. 2019 Sep 3;15(9):e1007348.
[button style="btn-default btn-sm" icon="glyphicon glyphicon-share" align="left" type="link" target="true" title="PLoS Comp. Bio link" link="https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1007348" linkrel="" class="publication-buttons"] [button style="btn-default btn-sm" icon="glyphicon glyphicon-download-alt" align="left" type="link" target="true" title="PDF Mirror" link="http://www.moseslab.csb.utoronto.ca/Lu_Moses_PLoS_Comp_Bio_2019.pdf" linkrel="" class="publication-buttons"] [button style="btn-default btn-sm" icon="glyphicon glyphicon-share" align="left" type="link" target="true" title="PubMed Abstract" link="https://www.ncbi.nlm.nih.gov/pubmed/31479439" linkrel="" class="publication-buttons"] [label class="publication-types"]Article[/label]
[label class="publication-tags"]Deep Learning[/label] [label class="publication-tags"]Self-Supervised[/label] [label class="publication-tags"]Image analysis[/label] [label class="publication-tags"]Subcellular localization[/label]

Molecular Evolution of Disordered Regions

Zarin et al. 2017
Zarin et al. 2017
Zarin et al. 2017
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Intrinsically Disordered Regions (or IDRs) are enigmatic protein regions that are involved in a wide variety of biological processes. Although they are widespread, they usually show little evolutionary conservation. Is this rapid evolution a sign that they are just "junk" protein, or do they facilitate evolutionary diversity? This question is also of medical relevance: when we find mutations in patients' IDRs we currently cannot tell what impact (if any) they are having.

LATEST PAPERS:

Pritišanac I, Vernon RM, Moses AM, Forman-Kay JD Entropy and Information within Intrinsically Disordered Protein Regions . Entropy 2019 21(7), 662
[button style="btn-default btn-sm" icon="glyphicon glyphicon-share" align="left" type="link" target="true" title="Entropy link" link="https://www.mdpi.com/1099-4300/21/7/662" linkrel="" class="publication-buttons"] [button style="btn-default btn-sm" icon="glyphicon glyphicon-download-alt" align="left" type="link" target="true" title="PDF Mirror" link="http://www.moseslab.csb.utoronto.ca/Pritisanac_Forman-Kay_Entropy_2019.pdf" linkrel="" class="publication-buttons"] [label class="publication-types"]Review[/label]
[label class="publication-tags"]Information theory[/label] [label class="publication-tags"]Biophysics[/label] [label class="publication-tags"]Intrinsically disordered[/label] [label class="publication-tags"]Evolution[/label]
Zarin T Sequence-function relationships in intrinsically disordered regions through the lens of evolution.
University of Toronto 2019 [button style="btn-default btn-sm" icon="glyphicon glyphicon-download-alt" align="left" type="link" target="true" title="Thesis Link" link="http://www.moseslab.csb.utoronto.ca/Zarin_Taraneh_201905_Phd_thesis.pdf" linkrel="" class="publication-buttons"] [label type="label-danger" class="publication-types"]PhD thesis[/label]
[label class="publication-tags"]Molecular evolution[/label] [label class="publication-tags"]Intrinsically disordered[/label] [label class="publication-tags"]Sequence divergence[/label][label class="publication-tags"]Biological function[/label]

Beautiful bioinformatics for genomics and proteomics

Davey et al. 2015
Lai et al. 2012
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Complete sequencing of genomes is now routine, and yields thousands of genes and proteins, and information about the genetic differences in populations. All of this data needs to be organized and analyzed: bioinformatics!

LATEST PAPERS:

Mehdi TF, Singh G, Mitchell JA, Moses AM. Variational Infinite Heterogeneous Mixture Model for Semi-supervised Clustering of Heart Enhancers. Bioinformatics 2019 Feb 7
[button style="btn-default btn-sm" icon="glyphicon glyphicon-share" align="left" type="link" target="true" title="Bioinformatics link" link="https://academic.oup.com/bioinformatics/advance-article/doi/10.1093/bioinformatics/btz064/5308600" linkrel="" class="publication-buttons"] [button style="btn-default btn-sm" icon="glyphicon glyphicon-download-alt" align="left" type="link" target="true" title="PDF Mirror" link="http://www.moseslab.csb.utoronto.ca/Mehdi_Moses_Bioinformatics_2019.pdf" linkrel="" class="publication-buttons"] [button style="btn-default btn-sm" icon="glyphicon glyphicon-share" align="left" type="link" target="true" title="PubMed Abstract" link="https://www.ncbi.nlm.nih.gov/pubmed/30753279" linkrel="" class="publication-buttons"] [label class="publication-types"]Article[/label]
[label class="publication-tags"]Regulatory networks[/label] [label class="publication-tags"]Transcription factors[/label] [label class="publication-tags"]Genomics[/label] [label class="publication-tags"]Machine Learning[/label]
Strome B, Hsu IS, Li Cheong Man M, Zarin T, Nguyen Ba A, Moses AM. Short linear motifs in intrinsically disordered regions modulate HOG signaling capacity. BMC Syst Biol. 2018 Jul 3;12(1):75.
[button style="btn-default btn-sm" icon="glyphicon glyphicon-share" align="left" type="link" target="true" title="BMC Systems Biology Link" link="https://bmcsystbiol.biomedcentral.com/articles/10.1186/s12918-018-0597-3" linkrel="" class="publication-buttons"] [button style="btn-default btn-sm" icon="glyphicon glyphicon-download-alt" align="left" type="link" target="true" title="PDF Mirror" link="http://www.moseslab.csb.utoronto.ca/Strome_Moses_BMC_Sys_Bio_201.pdf" linkrel="" class="publication-buttons"] [button style="btn-default btn-sm" icon="glyphicon glyphicon-share" align="left" type="link" target="true" title="PubMed Abstract" link="https://www.ncbi.nlm.nih.gov/pubmed/29970070" linkrel="" class="publication-buttons"][label class="publication-types"]Article[/label]
[label class="publication-tags"]Cell signaling[/label] [label class="publication-tags"]Saccharomyces cerevisiae[/label] [label class="publication-tags"]Mitogen-activated kinases[/label] [label class="publication-tags"]Intrinsically disordered regions[/label] [label class="publication-tags"]Short linear motifs[/label] [label class="publication-tags"]High osmotic glycerol pathway[/label]