FIREcaller: Detecting frequently interacting regions from Hi-C data

Crowley, Cheynna; Yang, Yuchen; Qiu, Yunjiang; Hu, Benxia; Abnousi, Armen; Lipiński, Jakub; Plewczyński, Dariusz; Wu, Di; Won, Hyejung; Ren, Bing; Hu, Ming; Li, Yun

doi:10.1016/j.csbj.2020.12.026

Cited by 23 publications

(20 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies from our and other groups have reported that enhancers with high local chromatin interactions, such as hub enhancers [ 7 ] and frequently interacting regions (FIREs) [ 31 , 32 ], play a profound role in gene regulation. FIREs are chromatin regions that show significantly high enrichment on local chromatin contacts.…”

Section: Resultsmentioning

confidence: 99%

“…As such, we next asked whether the three types of SEs are differentially enriched in local chromatin interactions. To this end, we first identified FIREs at day15 cells by using FIREcaller [ 31 ] and tested the overlap between SEs and FIREs. DN SEs are more enriched with FIREs than Con and TH SEs, while all three types of SEs show significant enrichment in FIREs compared to random genomic regions (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…We used FIREcaller [ 31 ] to detect frequently interacting regions from Hi-C data at 50kb resolution. Briefly, the raw Hi-C contact matrix was used as input and the total number of local interactions (<200kb) for each genomic locus was calculated as the raw FIRE score.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Mapping the evolving landscape of super-enhancers during cell differentiation

Kai

Zhu

et al. 2021

Genome Biol

View full text Add to dashboard Cite

Background Super-enhancers are clusters of enhancer elements that play critical roles in the maintenance of cell identity. Current investigations on super-enhancers are centered on the established ones in static cell types. How super-enhancers are established during cell differentiation remains obscure. Results Here, by developing an unbiased approach to systematically analyze the evolving landscape of super-enhancers during cell differentiation in multiple lineages, we discover a general trend where super-enhancers emerge through three distinct temporal patterns: conserved, temporally hierarchical, and de novo. The three types of super-enhancers differ further in association patterns in target gene expression, functional enrichment, and 3D chromatin organization, suggesting they may represent distinct structural and functional subtypes. Furthermore, we dissect the enhancer repertoire within temporally hierarchical super-enhancers, and find enhancers that emerge at early and late stages are enriched with distinct transcription factors, suggesting that the temporal order of establishment of elements within super-enhancers may be directed by underlying DNA sequence. CRISPR-mediated deletion of individual enhancers in differentiated cells shows that both the early- and late-emerged enhancers are indispensable for target gene expression, while in undifferentiated cells early enhancers are involved in the regulation of target genes. Conclusions In summary, our analysis highlights the heterogeneity of the super-enhancer population and provides new insights to enhancer functions within super-enhancers.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Mapping the evolving landscape of super-enhancers during cell differentiation

Kai

Zhu

et al. 2021

Genome Biol

View full text Add to dashboard Cite

show abstract

“…FIRE calling was carried out using the FIREcaller software (Crowley et al, 2021). The resolution for FIRE calling was 10 kb.…”

Section: Fire Callingmentioning

confidence: 99%

Profiling of 3D Genome Organization in Nasopharyngeal Cancer Needle Biopsy Patient Samples by a Modified Hi-C Approach

et al. 2021

View full text Add to dashboard Cite

Nasopharyngeal cancer (NPC), a cancer derived from epithelial cells in the nasopharynx, is a cancer common in China, Southeast Asia, and Africa. The three-dimensional (3D) genome organization of nasopharyngeal cancer is poorly understood. A major challenge in understanding the 3D genome organization of cancer samples is the lack of a method for the characterization of chromatin interactions in solid cancer needle biopsy samples. Here, we developed Biop-C, a modified in situ Hi-C method using solid cancer needle biopsy samples. We applied Biop-C to characterize three nasopharyngeal cancer solid cancer needle biopsy patient samples. We identified topologically associated domains (TADs), chromatin interaction loops, and frequently interacting regions (FIREs) at key oncogenes in nasopharyngeal cancer from the Biop-C heatmaps. We observed that the genomic features are shared at some important oncogenes, but the patients also display extensive heterogeneity at certain genomic loci. On analyzing the super enhancer landscape in nasopharyngeal cancer cell lines, we found that the super enhancers are associated with FIREs and can be linked to distal genes via chromatin loops in NPC. Taken together, our results demonstrate the utility of our Biop-C method in investigating 3D genome organization in solid cancers.

show abstract

“…Frequently Interacting Regions (FIREs) (Schmitt et al, 2016) was computed with FIREcaller R package (Crowley et al, 2021) at 10Kb resolution, with minor adjustments to fit our data format.…”

Section: D Featuresmentioning

confidence: 99%

Cis-Regulatory Hubs: a new 3D Model of Complex Disease Genetics with an Application to Schizophrenia

Mangnier

Joly-Beauparlant

Droit

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: The 3-dimensional (3D) conformation of the chromatin creates complex networks of noncoding regulatory regions (distal elements) and genes with important implications in gene regulation. Despite the importance of the role of noncoding regions in complex traits, little is known about their interplay within regulatory hubs and the implication in multigenic diseases like schizophrenia. Results: Here we show that cis-regulatory hubs (CRHs) in neurons highlight functional interactions between distal elements and promoters, providing a model to explain the epigenetic mechanisms involved in complex diseases. CRHs represent a new 3D model, where several distal elements interact to create a complex network of active genes. Indeed, we found that CRHs represent functional structures, showing higher transcriptional activity. In a disease context, CRHs highlighted strong enrichments in schizophrenia-associated genes, schizophrenia-associated SNPs and schizophrenia heritability compared to equivalent tissue and non-tissue-specific structures. Also, genes, by sharing the same distal elements, converge to common biological processes associated with schizophrenia. Finally, the results showed that in a complex disease etiology, small CRHs by linking fewer distal elements to promoters constitute a more informative structure than larger hubs. Conclusion: CRHs are a new 3D model of the chromatin interactions between gene promoters and their distal elements highlighting causal regulatory processes and providing a better understanding of complex disease etiology such as schizophrenia. Indeed, by providing a finer scale chromosome architecture, we have genetic and statistical evidence that CRHs represent a major advancement in 3D models to study the epigenetic underlying processes involved in complex traits.

show abstract

FIREcaller: Detecting frequently interacting regions from Hi-C data

Cited by 23 publications

References 42 publications

Mapping the evolving landscape of super-enhancers during cell differentiation

Mapping the evolving landscape of super-enhancers during cell differentiation

Profiling of 3D Genome Organization in Nasopharyngeal Cancer Needle Biopsy Patient Samples by a Modified Hi-C Approach

Cis-Regulatory Hubs: a new 3D Model of Complex Disease Genetics with an Application to Schizophrenia

Contact Info

Product

Resources

About