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Integrative Genome Modeling Platform reveals essentiality of rare contact events in 3D genome organizations

Boninsegna, Lorenzo and Yildirim, Asli and Polles, Guido and Quinodoz, Sofia A. and Finn, Elizabeth and Guttman, Mitchell and Zhou, Xianghong Jasmine and Alber, Frank (2021) Integrative Genome Modeling Platform reveals essentiality of rare contact events in 3D genome organizations. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20210824-174746931

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Abstract

A multitude of sequencing-based and microscopy technologies provide the means to unravel the relationship between the three-dimensional (3D) organization of genomes and key regulatory processes of genome function. However, it remains a major challenge to systematically integrate all available data sources to characterize the nuclear organization of genomes across different spatial scales. Here, we develop a multi-modal data integration approach to produce genome structures that are highly predictive for nuclear locations of genes and nuclear bodies, local chromatin compaction, and spatial segregation of functionally related chromatin. By performing a quantitative assessment of the predictive power of genome structures generated from different data combinations, we demonstrate that multimodal data integration can compensate for systematic errors and missing values in some of the data and thus, greatly increases accuracy and coverage of genome structure models. We also show that alternative combinations of different orthogonal data sources can converge to models with similar predictive power. Moreover, our study reveals the key contributions of low-frequency inter-chromosomal contacts (e.g., ''rare'' contact events) to accurately predicting the global nuclear architecture, including the positioning of genes and chromosomes. Overall, our results highlight the benefits of multi-modal data integration for genome structure analysis, available through the Integrative Genome structure Modeling (IGM) software package that we introduce here.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2021.08.22.457288DOIDiscussion Paper
ORCID:
AuthorORCID
Quinodoz, Sofia A.0000-0003-1862-5204
Guttman, Mitchell0000-0003-4748-9352
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This version posted August 23, 2021. This work was supported by the National Institutes of Health (grants U54DK107981 and 1UM1HG011593 to F.A), and an NSF CAREER grant (1150287 to F.A.). We thank the laboratories of Profs. Job Dekker (University of Massachusetts Medical School, UMass), Bas Van Steensel (Netherlands Cancer Institute, NKI), Tom Misteli (National Institutes of Health, NIH), and Andrew Belmont (University of Illinois Urbana-Champaign, UIUC) for kindly providing the experimental data (in situ Hi-C, lamina DamID, 3D HIPMap FISH, DNA SPRITE and SON TSAseq, respectively) used for generating and validating our genome models. The authors have declared no competing interest.
Funders:
Funding AgencyGrant Number
NIHU54DK107981
NIH1UM1HG011593
NSFDBI-1150287
DOI:10.1101/2021.08.22.457288
Record Number:CaltechAUTHORS:20210824-174746931
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210824-174746931
Official Citation:Integrative Genome Modeling Platform reveals essentiality of rare contact events in 3D genome organizations. Lorenzo Boninsegna, Asli Yildirim, Guido Polles, Sofia A Quinodoz, Elizabeth H Finn, Mitchell Guttman, Xianghong J Zhou, Frank Alber. bioRxiv 2021.08.22.457288; doi: https://doi.org/10.1101/2021.08.22.457288
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:110401
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:24 Aug 2021 18:17
Last Modified:16 Nov 2021 19:40

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