MIA-Sig: multiplex chromatin interaction analysis by signal processing and statistical algorithms

The single-molecule multiplex chromatin interaction data generated by emerging non-ligation-based 3D genome mapping technologies provide novel insights into high dimensional chromatin organization, yet introduce new computational challenges. We developed MIA-Sig (https://github.com/TheJacksonLaboratory/mia-sig.git), an algorithmic framework to de-noise the data, assess the statistical significance of chromatin complexes, and identify topological domains and inter-domain contacts. On chromatin immunoprecipitation (ChIP)-enriched data, MIA-Sig can clearly distinguish the protein-associated interactions from the non-specific topological domains.

[1]  B. Tabak,et al.  Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus , 2018, Cell.

[2]  S. Q. Xie,et al.  Complex multi-enhancer contacts captured by Genome Architecture Mapping (GAM) , 2017, Nature.

[3]  C. E. SHANNON,et al.  A mathematical theory of communication , 1948, MOCO.

[4]  J. Dekker,et al.  Structural and functional diversity of Topologically Associating Domains , 2015, FEBS letters.

[5]  James T. Robinson,et al.  Juicebox Provides a Visualization System for Hi-C Contact Maps with Unlimited Zoom. , 2016, Cell systems.

[6]  Minji Kim,et al.  ChIA-DropBox: a novel analysis and visualization pipeline for multiplex chromatin interactions , 2019, bioRxiv.

[7]  Yijun Ruan,et al.  Evolutionarily Conserved Principles Predict 3D Chromatin Organization. , 2017, Molecular cell.

[8]  Dariusz M Plewczynski,et al.  CTCF-Mediated Human 3D Genome Architecture Reveals Chromatin Topology for Transcription , 2015, Cell.

[9]  G. Ciriello,et al.  Comparison of computational methods for the identification of topologically associating domains , 2018, Genome Biology.

[10]  Daniel Capurso,et al.  Multiplex chromatin interactions with single-molecule precision , 2019, Nature.

[11]  Aaron R. Quinlan,et al.  BIOINFORMATICS APPLICATIONS NOTE , 2022 .

[12]  Noam Kaplan,et al.  The Hitchhiker's guide to Hi-C analysis: practical guidelines. , 2015, Methods.

[13]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[14]  Philippe Collas,et al.  Long-range interactions between topologically associating domains shape the four-dimensional genome during differentiation , 2019, Nature Genetics.

[15]  E. Liu,et al.  An Oestrogen Receptor α-bound Human Chromatin Interactome , 2009, Nature.

[16]  Stéphane Mallat,et al.  A Theory for Multiresolution Signal Decomposition: The Wavelet Representation , 1989, IEEE Trans. Pattern Anal. Mach. Intell..

[17]  Sang Joon Kim,et al.  A Mathematical Theory of Communication , 2006 .

[18]  I. Amit,et al.  Comprehensive mapping of long range interactions reveals folding principles of the human genome , 2011 .

[19]  Allon M Klein,et al.  Scrublet: Computational Identification of Cell Doublets in Single-Cell Transcriptomic Data. , 2019, Cell systems.