title: Using first passage statistics to extract environmentally dependent amino acid correlations.
abstract: In this work, we study the first passage statistics of amino acid primary sequences, that is the probability of observing an amino acid for the first time at a certain number of residues away from a fixed amino acid. By using this rich mathematical framework, we are able to capture the background distribution for an organism, and infer lengths at which the first passage has a probability that differs from what is expected. While many features of an organism's genome are due to natural selection, others are related to amino acid chemistry and the environment in which an organism lives, constraining the randomness of genomes upon which selection can further act. We therefore use this approach to infer amino acid correlations, and then study how these correlations vary across a wide range of organisms under a wide range of optimal growth temperatures. We find a nearly universal exponential background distribution, consistent with the idea that most amino acids are globally uncorrelated from other amino acids in genomes. When we are able to extract significant correlations, these correlations are reliably dependent on optimal growth temperature, across phylogenetic boundaries. Some of the correlations we extract, such as the enhanced probability of finding, for the first time, a cysteine three residues away from a cysteine or glutamic acid two residues away from an arginine, likely relate to thermal stability. However, other correlations, likely appearing on alpha helical surfaces, have a less clear physiochemical interpretation and may relate to thermal stability or unusual metabolic properties of organisms that live in a high temperature environment.
authors.affiliation: Departments of Medicine, Division of Hematology and Medical Oncology, and Pathology, and the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America, 2. The Simons Center for Systems Biology, Institute for Advanced Study, Princeton, New Jersey, United States of America.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Greenbaum
authors.affiliation: Center for Studies in Physics and Biology, The Rockefeller University, New York, New York, United States of America; Department of Physics, University of Arkansas at Little Rock, Little Rock, Arkansas, United States of America.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.affiliation: The Simons Center for Systems Biology, Institute for Advanced Study, Princeton, New Jersey, United States of America; Center for Studies in Physics and Biology, The Rockefeller University, New York, New York, United States of America.
authors.forename: Albert
authors.initials: A
authors.lastname: Libchaber
mesh_terms: D000596:Amino Acids; D019295:Computational Biology / Q000379:methods*; D017753:Ecosystem; D004777:Environment; D023281:Genomics; D013696:Temperature
chemical_list: D000596:Amino Acids