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
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.
|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
|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
Microscope images are big data
Lu et al. 2016
Handfield et al. 2015
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.
|Lu AX, Chong YT, Hsu IS, Strome B, Handfield LF, Kraus O, Andrews BJ, Moses AM. Integrating images from multiple microscopy screens reveals diverse patterns of change in the subcellular localization of proteins. eLife 2018;7:e31872.
eLife Link PDF Mirror PubMed AbstractArticle
|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
Molecular Evolution of Disordered Regions
Zarin et al. 2017
Zarin et al. 2017
Zarin et al. 2017
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.
|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
|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
Beautiful bioinformatics for genomics and proteomics
Davey et al. 2015
Lai et al. 2012
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!
|Liku ME, Legere EA, Moses AM NoLogo: a new statistical model highlights the diversity and suggests new classes of Crm1-dependent nuclear export signals. BMC Bioinformatics. 2018 7:Feb 27;19(1):65.
BMC bioinformatics Link PDF Mirror PubMed AbstractArticle
|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