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:

Douglas GM, Wilson MD, Moses AM. Decreased Transcription Factor Binding Levels Nearby Primate Pseudogenes Suggest Regulatory Degeneration. Mol. Biol. Evol. 2016 Feb 16.
Molecular Biology and Evolution Link PDF Mirror PubMed Abstract Article
Pseudoenhancer Regulatory evolution ChIP-seq Neutral evolution Histone modifications
Davey NE, Cyert MS, Moses AM. Short linear motifs–ex nihilo evolution of protein regulation. Cell Comm. Sig. 2015 Nov 21.
Cell Communication and Signaling Link PDF Mirror PubMed Abstract Article
Motifs Short linear motifs SLiMs Cis-regulatory elements RNA motifs Evolution Modularity Protein evolution

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, Moses AM. An Unsupervised kNN Method to Systematically Detect Changes in Protein Localization in High-Throughput Microscopy Images. PLoS One 2016 Jul 21;11(7):e0158712.
PLoS One Link PDF Mirror PubMed Abstract Article
Imaging techniques Cell cycle and cell division Genetic screens Subcellular localization Image analysis Saccharomyces cerevisiae Green fluorescent protein Perception
Handfield LF, Strome B, Chong YT, Moses AM. Local statistics allow quantification of cell-to-cell variability from high-throughput microscope images. Bioinformatics 2014 Nov 14.
Bioinformatics Link PDF Mirror PubMed Abstract Article
Bioinformatics Statistics Microscopy Imaging Subcellular localization Cell-to-cell variability

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:

Zarin T, Tsai CN, Nguyen Ba AN, Moses AM. Selection maintains signaling function of a highly diverged intrinsically disordered region. PNAS 2017 Feb 21;114(8).
PNAS Link PDF Mirror PubMed Abstract Article
Evolution Intrinsically disordered Quantitative trait Phylogenetic comparative method Stabilizing selection
Khan T, Douglas GM, Patel P, Nguyen Ba AN, Moses AM. Polymorphism Analysis Reveals Reduced Negative Selection and Elevated Rate of Insertions and Deletions in Intrinsically Disordered Protein Regions. Genome Biol Evol. 2015 Jun 4.
Genome Biology and Evolution Link PDF Mirror PubMed Abstract Article
Negative Selection Indels SNP Intrinsically Disordered Protein

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:

Nguyen Ba AN, Strome B, Osman S, Legere EA, Zarin T, Moses AM. Parallel reorganization of protein function in the spindle checkpoint pathway through evolutionary paths in the fitness landscape that appear neutral in laboratory experiments. PLoS Genetics 2017 Apr 14;13(4).
PLoS Genetics Link PDF Mirror PubMed Abstract Article
Saccharomyces cerevisiae Evolutionary genetics Molecular evolution Natural selection Gene duplication Fungal evolution Green fluorescent protein Sequence motif analysis
Davey NE, Cyert MS, Moses AM. Short linear motifs–ex nihilo evolution of protein regulation. Cell Comm. Sig. 2015 Nov 21.
Cell Communication and Signaling Link PDF Mirror PubMed Abstract Article
Motifs Short linear motifs SLiMs Cis-regulatory elements RNA motifs Evolution Modularity Protein evolution