2021
DOI: 10.1371/journal.pcbi.1009669
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Extracting multi-way chromatin contacts from Hi-C data

Abstract: There is a growing realization that multi-way chromatin contacts formed in chromosome structures are fundamental units of gene regulation. However, due to the paucity and complexity of such contacts, it is challenging to detect and identify them using experiments. Based on an assumption that chromosome structures can be mapped onto a network of Gaussian polymer, here we derive analytic expressions for n-body contact probabilities (n > 2) among chromatin loci based on pairwise genomic contact frequencies ava… Show more

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Cited by 19 publications
(12 citation statements)
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“…We next asked if the method accounts for higher-order structures, such as three-way contacts, discovered in GAM 27 , 28 and SPRITE experiments 26 and imaging experiments 47 , and predicted by the theory 64 , 65 . First, we computed the probability of co-localization of loci triplets, π i j k ( a ) = Pr( r i j < a , r i k < a , r j k < a ) where a is the distance threshold for contact formation ( r i j < a implies a contact).…”
Section: Resultsmentioning
confidence: 99%
“…We next asked if the method accounts for higher-order structures, such as three-way contacts, discovered in GAM 27 , 28 and SPRITE experiments 26 and imaging experiments 47 , and predicted by the theory 64 , 65 . First, we computed the probability of co-localization of loci triplets, π i j k ( a ) = Pr( r i j < a , r i k < a , r j k < a ) where a is the distance threshold for contact formation ( r i j < a implies a contact).…”
Section: Resultsmentioning
confidence: 99%
“…It is appreciated that multi-way interactions can help elucidate chromatin hubs consisting of multiple genes and/or regulator elements [24][25][26]. We expect more research in this direction with more technological and computational methods developed [24,26,109]. Second, little research has been carried out to interrogate inter-chromosomal interactions, due to the sparsity of contacts between DNA segments from different chromosomes.…”
Section: Discussionmentioning
confidence: 99%
“…However, the null element is not necessarily equivalent to the zero value of the contact probability. Although the null-value contribution has been eliminated when calculating the cost function ( Liu et al , 2021 ), PHi-C2 has not implemented it. The iterative optimization process depends on the input matrix size ( Shinkai et al , 2020b ), while 100 × 100–500 × 500 is a good and practical input matrix size according to the genomic region of interest ( Supplementary Table S3 ).…”
Section: Implementation and Benchmarksmentioning
confidence: 99%