Characterizing the 3D structure and dynamics of chromosomes and proteins in a common contact matrix framework. Issue 16 (10th July 2018)

• Record Type: Journal Article
• Authors: Lindsay, Richard J; Pham, Bill; Shen, Tongye; McCord, Rachel Patton
• Is Part Of: Nucleic acids research. Volume 46:Issue 16(2018)
• Page Start: 8143
• Page End: 8152
• Publication Date: 2018-07-10
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gky604
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: Conformational ensembles of biopolymers, whether proteins or chromosomes, can be described using contact matrices. Principal component analysis (PCA) on the contact data has been used to interrogate both protein and chromosome structures and/or dynamics. However, as these fields have developed separately, variants of PCA have emerged. Previously, a variant we hereby term Implicit-PCA (I-PCA) has been applied to chromosome contact matrices and revealed the spatial segregation of active and inactive chromatin. Separately, Explicit-PCA (E-PCA) has previously been applied to proteins and characterized their correlated structure fluctuations. Here, we swapped analysis methods (I-PCA and E-PCA), applying each to a different biopolymer type (chromosome or protein) than the one for which they were initially developed. We find that applying E-PCA to chromosome distance matrices derived from microscopy data can reveal the dominant motion (concerted fluctuation) of these chromosomes. Further, by applying E-PCA to Hi-C data across the human blood cell lineage, we isolated the aspects of chromosome structure that most strongly differentiate cell types. Conversely, when we applied I-PCA to simulation snapshots of proteins, the major component reported the consensus features of the structure, making this a promising approach for future analysis of semi-structured proteins.