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Capurso, D.

Publications and source records attributed to Capurso, D..

4 recordsLinked to original sources

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.

genomics↗

ChIA-DropBox: a novel analysis and visualization pipeline for multiplex chromatin interactions

ChIA-Drop is a new experimental method for mapping multiplex chromatin interactions with single-molecule precision by barcoding chromatin complexes inside microfluidics droplets, followed by pooled DNA sequencing. The chromatin DNA reads with the same droplet-specific barcodes are inferred to be derived from the same chromatin interaction complex. Here, we describe an integrated computational pipeline, named ChIA-DropBox, that is specifically designed for reconstructing chromatin reads in each droplet and refining multiplex chromatin complexes from raw ChIA-Drop sequencing reads, and then visualizing the results. First, ChIA-DropBox maps and filters sequencing reads, and then reconstructs the \"chromatin droplets\" by parsing the barcode sequences and grouping together chromatin reads with the same barcode. Based on the concept of chromosome territories that most chromatin interactions take place within the same chromosome, potential mixing up of chromatin complexes derived from different chromosomes could be readily identified and separated. Accordingly, ChIA-DropBox refines these \"chromatin droplets\" into purely intra-chromosomal chromatin complexes, ready for downstream analysis. For visualization, ChIA-DropBox converts the ChIA-Drop data to pairwise format and automatically generates input files for viewing 2D contact maps in Juicebox and viewing loops in BASIC Browser. Finally, ChIA-DropBox introduces a new browser, named ChIA-View, for interactive visualization of multiplex chromatin interactions.

bioinformatics↗

ChIA-PIPE: A fully automated pipeline for ChIA-PET data analysis and visualization

ChIA-PET enables the genome-wide discovery of chromatin interactions involving specific protein factors, with base-pair resolution. Interpreting ChIA-PET data depends on having a robust analytic pipeline. Here, we introduce ChIA-PIPE, a fully automated pipeline for ChIA-PET data processing, quality assessment, analysis, and visualization. ChIA-PIPE performs linker filtering, read mapping, peak calling, loop calling, chromatin-contact-domain calling, and can resolve allele-specific peaks and loops. ChIA-PIPE also automates quality-control assessment for each dataset. Furthermore, ChIA-PIPE generates input files for visualizing 2D contact maps with Juicebox and HiGlass, and provides a new dockerized visualization tool for high-resolution, browser-based exploration of peaks and loops. With minimal adjusting, ChIA-PIPE can also be suited for the analysis of other related chromatin-mapping data.

bioinformatics↗

Multiplex Chromatin Interaction Analysis with Single-Molecule Precision

We describe a microfluidics-based strategy for genome-wide analysis of multiplex chromatin interactions with single-molecule precision. In multiplex chromatin interaction analysis (multi-ChIA), individual chromatin complexes are partitioned into droplets that contain a gel bead with unique DNA barcode, in which tethered chromatin DNA fragments are barcoded and amplified for sequencing and mapping to demarcate chromatin contacts. Thus, multi-ChIA has the unprecedented ability to uncover multiplex chromatin interactions at single-molecule level, which has been impossible using previous methods that rely on analyzing pairwise contacts via proximity ligation. We demonstrate that multiplex chromatin interactions predominantly contribute to topologically associated domains, and clusters of gene promoters and enhancers provide a fundamental topological framework for co-transcriptional regulation.

genomics↗