Generative modeling of multi-mapping reads with mHi-C advances analysis of Hi-C studies

Generative modeling of multi-mapping reads with mHi-C advances analysis of Hi-C studies

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Current Hi-C analysis approaches are unable to account for reads that align to multiple locations, and hence underestimate biological signal from repetitive regions of genomes.We developed and validated mHi-C, a multi-read mapping strategy to probabilistically allocate Hi-C multi-reads.mHi-C exhibited superior performance over utilizing 2006 nissan altima radio only uni-reads and heuristic approaches aimed at rescuing multi-reads on benchmarks.

Specifically, mHi-C increased the sequencing depth by an average of 20% resulting in higher reproducibility of contact matrices and detected interactions across biological replicates.The impact of the multi-reads on the detection of significant interactions is influenced marginally by the relative contribution of multi-reads to the sequencing depth click here compared to uni-reads, cis-to-trans ratio of contacts, and the broad data quality as reflected by the proportion of mappable reads of datasets.Computational experiments highlighted that in Hi-C studies with short read lengths, mHi-C rescued multi-reads can emulate the effect of longer reads.

mHi-C also revealed biologically supported bona fide promoter-enhancer interactions and topologically associating domains involving repetitive genomic regions, thereby unlocking a previously masked portion of the genome for conformation capture studies.