Pairtools: from sequencing data to chromosome contacts

Abdennur, Nezar; Fudenberg, Geoffrey; Flyamer, Ilya M.; Galitsyna, Aleksandra A.; Goloborodko, Anton; Imakaev, Maxim; Venev, Sergey V.

doi:10.1101/2023.02.13.528389

Cited by 64 publications

(41 citation statements)

References 76 publications

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“…18 Briefly, paired-end reads were aligned to the UCSC hg38 genome using bowtie2 (v2.3.5.1), and aligned read mates were subsequently processed with pairtools (v0.3.0) to remove PCR duplicates and non-uniquely mapped reads, index reads, and filter to retain only reads with both mates within the captured region ( Extended Data Table 3 ). 17,51,52 Read counts were binned across the genome for 50bp bins to coarser resolutions using cooler (v0.8.11). 53 Resulting contact matrices were balanced using iterative correction and eigendecomposition (ICE) within the captured region.…”

Section: Methodsmentioning

confidence: 99%

IntegrativePTENEnhancer Discovery Reveals a New Model of Enhancer Organization

Cerda-Smith,

Hutchinson,

Liu

et al. 2023

Preprint

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Enhancers possess both structural elements mediating promoter looping and functional elements mediating gene expression. Traditional models of enhancer-mediated gene regulation imply genomic overlap or immediate adjacency of these elements. We test this model by combining densely-tiled CRISPRa screening with nucleosome-resolution Region Capture Micro-C topology analysis. Using this integrated approach, we comprehensively define the cis-regulatory landscape for the tumor suppressor PTEN, identifying and validating 10 distinct enhancers and defining their 3D spatial organization. Unexpectedly, we identify several long-range functional enhancers whose promoter proximity is facilitated by chromatin loop anchors several kilobases away, and demonstrate that accounting for this spatial separation improves the computational prediction of validated enhancers. Thus, we propose a new model of enhancer organization incorporating spatial separation of essential functional and structural components.

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Section: Methodsmentioning

confidence: 99%

IntegrativePTENEnhancer Discovery Reveals a New Model of Enhancer Organization

Cerda-Smith,

Hutchinson,

Liu

et al. 2023

Preprint

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“…4 replicates of K562 MNase CTCF HiChIP data were aligned to the reference genome using the BWA-MEM algorithm 41 . Ligation events were then recorded using pairtools parse v. 0.3.0 42 , PCR duplicates were removed, and the final pairs and bam files were generated. HiChIP loop calls were then made using FitHiChIP Peak to Peak 29 with 2.5kb loop anchor bin size.…”

Section: Methodsmentioning

confidence: 99%

High-resolution CTCF footprinting reveals impact of chromatin state on cohesin extrusion dynamics

Sept,

Tak,

Cerda-Smith

et al. 2023

Preprint

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DNA looping is vital for establishing many enhancer-promoter interactions. While CTCF is known to anchor many cohesin-mediated loops, the looped chromatin fiber appears to predominantly exist in a poorly characterized actively extruding state. To better characterize extruding chromatin loop structures, we used CTCF MNase HiChIP data to determine both CTCF binding at high resolution and 3D contact information. Here we present FactorFinder, a tool that identifies CTCF binding sites at near base-pair resolution. We leverage this substantial advance in resolution to determine that the fully extruded (CTCF-CTCF) state is rare genome-wide with locus-specific variation from ~1-10%. We further investigate the impact of chromatin state on loop extrusion dynamics, and find that active enhancers and RNA Pol II impede cohesin extrusion, facilitating an enrichment of enhancer-promoter contacts in the partially extruded loop state. We propose a model of topological regulation whereby the transient, partially extruded states play active roles in transcription.

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“…To process the HiC data, we first mapped the HiC data to the primary genome assembly using BWA-mem version 0.7.17 (Li & Durbin, 2009) with the arguments -SP . The mapped reads were then parsed and filtered using pairtools version 1.0.2 (Open2C et al , 2023). To parse the aligned Hi-C reads, we used the options –no-flip –dd-columns mapq –walks-policy mask .…”

Section: Methodsmentioning

confidence: 99%

High quality genome assembly of the brown hare (Lepus europaeus) with chromosome-level scaffolding

Michell,

Collins,

Laine

et al. 2023

Preprint

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Here we present a high-quality genome assembly of the mountain hare (Lepus timidusL.), based on a fibroblast cell line of a male specimen from Ilomantsi, Eastern Finland. The mountain hare represents the first Finnish contribution to the European Reference Genome Atlas pilot effort to generate reference genomes for European biodiversity.The genome was assembled using 25X PacBio HiFi sequencing data and scaffolded utilizing a Hi-C chromosome structure capture approach. After manual curation, the assembled genome length was 2,930,972,003 bp with N50 125.8Mb. 93.16% of the assembly could be assigned to 25 identified chromosomes (23 autosomes plus X and Y), matching the published karyotype. The chromosomes were named according to size. The genome has a high degree of completeness based on the BUSCO score (mammalia_odb10 database), Complete: 96.1% [Single copy: 93.1%, Duplicated: 3.0%], Fragmented 0.8%, and Missing 2.9%. The mitochondrial genome of the cell line was sequenced and assembled separately.Compared to the previous pseudoreference genome ofL. timidusssp.hibernicusBell, assembled using the rabbit genome, this new reference genome represents the nominal subspecies and the species-specific chromosomal conformation. In addition to providing a useful comparison for population studies, the genome can offer insight into the chromosomal evolution among Glires in general and Lagomorpha in particular. The chromosomal assembly of the genome also demonstrates that the cell line has not gone through karyotypic changes during culture.

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Pairtools: from sequencing data to chromosome contacts

Cited by 64 publications

References 76 publications

IntegrativePTENEnhancer Discovery Reveals a New Model of Enhancer Organization

IntegrativePTENEnhancer Discovery Reveals a New Model of Enhancer Organization

High-resolution CTCF footprinting reveals impact of chromatin state on cohesin extrusion dynamics

High quality genome assembly of the brown hare (Lepus europaeus) with chromosome-level scaffolding

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