Resolving spatial inconsistencies in chromosome conformation measurements

Geet Duggal, Rob Patro, Emre Sefer, Hao Wang, Darya Filippova, Samir Khuller, Carl Kingsford*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Background: Chromosome structure is closely related to its function and Chromosome Conformation Capture (3C) is a widely used technique for exploring spatial properties of chromosomes. 3C interaction frequencies are usually associated with spatial distances. However, the raw data from 3C experiments is an aggregation of interactions from many cells, and the spatial distances of any given interaction are uncertain.Results: We introduce a new method for filtering 3C interactions that selects subsets of interactions that obey metric constraints of various strictness. We demonstrate that, although the problem is computationally hard, near-optimal results are often attainable in practice using well-designed heuristics and approximation algorithms. Further, we show that, compared with a standard technique, this metric filtering approach leads to (a) subgraphs with higher statistical significance, (b) lower embedding error, (c) lower sensitivity to initial conditions of the embedding algorithm, and (d) structures with better agreement with light microscopy measurements. Our filtering scheme is applicable for a strict frequency-to-distance mapping and a more relaxed mapping from frequency to a range of distances.Conclusions: Our filtering method for 3C data considers both metric consistency and statistical confidence simultaneously resulting in lower-error embeddings that are biologically more plausible.

Original languageEnglish (US)
Article number8
JournalAlgorithms for Molecular Biology
Volume8
Issue number1
DOIs
StatePublished - Mar 9 2013

Keywords

  • 3C
  • Chromosome conformation capture
  • Graph embedding
  • Metric violations
  • Triangle inequality

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology
  • Computational Theory and Mathematics
  • Applied Mathematics

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