Generative modeling of multi-mapping reads with mHi-C advances analysis of Hi-C studies
| Autor: | Ye Zheng, Sunduz Keles, Ferhat Ay |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Mouse QH301-705.5 Computer science Science Systems biology Computational biology probabilistic modeling Genome General Biochemistry Genetics and Molecular Biology Deep sequencing Cell Line Generative modeling 03 medical and health sciences 0302 clinical medicine Hi-C Humans Computer Simulation Biology (General) Promoter Regions Genetic multi-reads Probability General Immunology and Microbiology Heuristic General Neuroscience Reproducibility of Results chromosome chromatin capture Genomics General Medicine Repetitive Regions Short read Chromatin Tools and Resources Enhancer Elements Genetic 030104 developmental biology Medicine 030217 neurology & neurosurgery Computational and Systems Biology Human |
| Zdroj: | eLife, Vol 8 (2019) eLife |
| ISSN: | 2050-084X |
| Popis: | 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 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 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. |
| Databáze: | OpenAIRE |
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