title: Unveiling Contacts within Macromolecular Assemblies by Solving Minimum Weight Connectivity Inference (MWC) Problems.
abstract: Consider a set of oligomers listing the subunits involved in subcomplexes of a macromolecular assembly, obtained e.g. using native mass spectrometry or affinity purification. Given these oligomers, connectivity inference (CI) consists of finding the most plausible contacts between these subunits, and minimum connectivity inference (MCI) is the variant consisting of finding a set of contacts of smallest cardinality. MCI problems avoid speculating on the total number of contacts but yield a subset of all contacts and do not allow exploiting a priori information on the likelihood of individual contacts. In this context, we present two novel algorithms, MILP-W and MILP-WB. The former solves the minimum weight connectivity inference (MWCI), an optimization problem whose criterion mixes the number of contacts and their likelihood. The latter uses the former in a bootstrap fashion to improve the sensitivity and the specificity of solution sets.Experiments on three systems (yeast exosome, yeast proteasome lid, human eIF3), for which reference contacts are known (crystal structure, cryo electron microscopy, cross-linking), show that our algorithms predict contacts with high specificity and sensitivity, yielding a very significant improvement over previous work, typically a twofold increase in sensitivity.The software accompanying this paper is made available and should prove of ubiquitous interest whenever connectivity inference from oligomers is faced.
authors: From the ‖Inria Sophia-Antipolis (Algorithms-Biology-Structure), 06902 Sophia Antipolis, France;
authors: Deepesh
authors: D
authors: Agarwal
authors: ‡Univ. Nice Sophia Antipolis, CNRS, I3S, UMR 7271, 06900 Sophia Antipolis, France; §Inria Sophia Antipolis (COATI), 06902 Sophia Antipolis, France.
authors: Christelle
authors: C
authors: Caillouet
authors: ‡Univ. Nice Sophia Antipolis, CNRS, I3S, UMR 7271, 06900 Sophia Antipolis, France; §Inria Sophia Antipolis (COATI), 06902 Sophia Antipolis, France.
authors: David
authors: D
authors: Coudert
authors: From the ‖Inria Sophia-Antipolis (Algorithms-Biology-Structure), 06902 Sophia Antipolis, France; Frederic.Cazals@inria.fr.
authors: Frederic
authors: F
authors: Cazals
mesh_terms: D000465:Algorithms; D039621:Eukaryotic Initiation Factor-3 / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism*; D008962:Models, Theoretical; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism
chemical_list: D039621:Eukaryotic Initiation Factor-3; D046911:Macromolecular Substances; D021122:Protein Subunits; D046988:Proteasome Endopeptidase Complex