Journal
NUCLEIC ACIDS RESEARCH
Volume 46, Issue 16, Pages 8143-8152Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gky604
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Funding
- National Institute for Health Research of England
- UK Biotechnology and Biological Research Council [BB/J004480/1]
- University of Tennessee
- UK Medical Research Council [MR/L007150/1]
- MRC [MR/L007150/1] Funding Source: UKRI
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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.
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