scholarly journals Genome-wide profiling in colorectal cancer identifies PHF19 and TBC1D16 as oncogenic super enhancers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qing-Lan Li ◽  
Xiang Lin ◽  
Ya-Li Yu ◽  
Lin Chen ◽  
Qi-Xin Hu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Cancer Patient ◽  
Nucleotide Polymorphisms ◽  
Rna Seq ◽  
Motif Analysis ◽  
Single Nucleotide ◽  
Super Enhancer ◽  
Genome Wide ◽  
Functional Factors ◽  
Cancer Tissues

AbstractColorectal cancer is one of the most common cancers in the world. Although genomic mutations and single nucleotide polymorphisms have been extensively studied, the epigenomic status in colorectal cancer patient tissues remains elusive. Here, together with genomic and transcriptomic analysis, we use ChIP-Seq to profile active enhancers at the genome wide level in colorectal cancer paired patient tissues (tumor and adjacent tissues from the same patients). In total, we sequence 73 pairs of colorectal cancer tissues and generate 147 H3K27ac ChIP-Seq, 144 RNA-Seq, 147 whole genome sequencing and 86 H3K4me3 ChIP-Seq samples. Our analysis identifies 5590 gain and 1100 lost variant enhancer loci in colorectal cancer, and 334 gain and 121 lost variant super enhancer loci. Multiple key transcription factors in colorectal cancer are predicted with motif analysis and core regulatory circuitry analysis. Further experiments verify the function of the super enhancers governing PHF19 and TBC1D16 in regulating colorectal cancer tumorigenesis, and KLF3 is identified as an oncogenic transcription factor in colorectal cancer. Taken together, our work provides an important epigenomic resource and functional factors for epigenetic studies in colorectal cancer.

scholarly journals Genome-wide profiling of active enhancers in colorectal cancer

2020 ◽  
Author(s):  
Min Wu ◽  
Qinglan Li ◽  
Xiang Lin ◽  
Ya-Li Yu ◽  
Lin Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Whole Genome ◽  
Cancer Cell Migration ◽  
Rna Seq ◽  
Motif Analysis ◽  
Super Enhancer ◽  
Genome Wide ◽  
The World ◽  
Functional Factors ◽  
Oncogenic Transcription Factor

Abstract Colorectal cancer (CRC) is one of the most common cancers in the world. Although genomic mutations and SNPs have been extensively studied, the epigenomic status in CRC patient tissues remains elusive. Here, we profiled active enhancers genome-widely in paired CRC patient tissues through H3K27ac ChIP-Seq, together with genomic and transcriptomic analysis. Totally we sequenced 73 pairs of CRC tissues and generated 147 H3K27ac ChIP-Seq, 144 RNA-Seq, 147 whole genome sequencing and 86 H3K4me3 ChIP-Seq files. Our analysis discovered 5590 gain variant enhancer loci (VEL) and 1100 lost VELs in CRC, and 334 gain variant super enhancer loci (VSEL) and 121 lost VSELs. Multiple key transcription factors in CRC were predicted with motif analysis and core regulatory circuitry analysis. Further experiments verified the functions of 6 super enhancers governing PHF19, LIF, SLC7A5, CYP2S1, RNF43 and TBC1D16 in regulating cancer cell migration, and we identified KLF3 as a novel oncogenic transcription factor in CRC. Taken together, our work provides important epigenomic resource and novel functional factors for epigenetic studies in CRC.

scholarly journals Variation rs9929218 and Risk of the Colorectal Cancer and Adenomas: A Meta-analysis

2020 ◽  
Author(s):  
Huiyan Wang ◽  
Dongying Gu ◽  
Miao Yu ◽  
Yanjun Hu ◽  
Zhe Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Colorectal ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Accurate Approximation ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Different Populations

Abstract Backgrounds: Genome-wide association studies (GWAS) have identified multiple common CRC-related (colorectal cancer) SNPs (single nucleotide polymorphisms) including the Cadherin 1(CDH1) rs9929218 may act by increasing the risk of colorectal cancer, colorectal adenoma, or both. These studies, however, reported inconsistent associations. Methods: To derive a more accurate approximation of the connection, we carried out a meta-analysis of 12 published pieces of research including 11,590 controls and 8,192 cases. We used odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the associations' strength.Results: Meta-analysis implied considerable association between CRC and rs9929218 (OR = 1.21, 95%CI 1.04-1.42 for GG versus AA; OR = 1.22, 95%CI 1.05-1.42 for GG/AG versus AA).In the subgroup analyses, significantly increased risks were found among Europeans.Conclusions: In summary, our meta-analysis studies in different populations confirmed that SNP rs9929218 is significantly associated with CRC risk and that this variant may have a greater impact on Europeans.

scholarly journals Variation rs9929218 and risk of the colorectal Cancer and adenomas: A meta-analysis

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Huiyan Wang ◽  
Dongying Gu ◽  
Miao Yu ◽  
Yanjun Hu ◽  
Zhe Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Colorectal ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Accurate Approximation ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Different Populations

Abstract Backgrounds Genome-wide association studies (GWAS) have identified multiple common CRC-related (colorectal cancer) SNPs (single nucleotide polymorphisms) including the Cadherin 1(CDH1) rs9929218 may act by increasing the risk of colorectal cancer, colorectal adenoma, or both. These studies, however, reported inconsistent associations. Methods To derive a more accurate approximation of the connection, we carried out a meta-analysis of 12 published pieces of research including 11,590 controls and 8192 cases. We used odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the associations’ strength. Results Meta-analysis implied considerable association between CRC and rs9929218 (OR = 1.21, 95%CI 1.04–1.42 for GG versus AA; OR = 1.22, 95%CI 1.05–1.42 for GG/AG versus AA). In the subgroup analyses, significantly increased risks were found among Europeans. Conclusions In summary, our meta-analysis studies in different populations confirmed that SNP rs9929218 is significantly associated with CRC risk and that this variant may have a greater impact on Europeans.

EpiPen: An R Package to Investigate Two-Locus Epistatic Models

2014 ◽  
Vol 17 (4) ◽  
Author(s):  
Raymond K. Walters ◽  
Charles Laurin ◽  
Gitta H. Lubke
Keyword(s):  
Power Analysis ◽  
R Package ◽  
Simulation Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Epistatic Interactions ◽  
Model Interpretation ◽  
Genome Wide ◽  
Using Data ◽  
Power Analyses

Epistasis is a growing area of research in genome-wide studies, but the differences between alternative definitions of epistasis remain a source of confusion for many researchers. One problem is that models for epistasis are presented in a number of formats, some of which have difficult-to-interpret parameters. In addition, the relation between the different models is rarely explained. Existing software for testing epistatic interactions between single-nucleotide polymorphisms (SNPs) does not provide the flexibility to compare the available model parameterizations. For that reason we have developed an R package for investigating epistatic and penetrance models, EpiPen, to aid users who wish to easily compare, interpret, and utilize models for two-locus epistatic interactions. EpiPen facilitates research on SNP-SNP interactions by allowing the R user to easily convert between common parametric forms for two-locus interactions, generate data for simulation studies, and perform power analyses for the selected model with a continuous or dichotomous phenotype. The usefulness of the package for model interpretation and power analysis is illustrated using data on rheumatoid arthritis.

scholarly journals Genomic Analyses of Globodera pallida, A Quarantine Agricultural Pathogen in Idaho

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 363
Author(s):  
Sulochana K. Wasala ◽  
Dana K. Howe ◽  
Louise-Marie Dandurand ◽  
Inga A. Zasada ◽  
Dee R. Denver
Keyword(s):  
Genetic Variation ◽  
Potato Production ◽  
Globodera Pallida ◽  
Fixation Index ◽  
Parasitic Nematodes ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Field Samples ◽  
Multiple Introduction

Globodera pallida is among the most significant plant-parasitic nematodes worldwide, causing major damage to potato production. Since it was discovered in Idaho in 2006, eradication efforts have aimed to contain and eradicate G. pallida through phytosanitary action and soil fumigation. In this study, we investigated genome-wide patterns of G. pallida genetic variation across Idaho fields to evaluate whether the infestation resulted from a single or multiple introduction(s) and to investigate potential evolutionary responses since the time of infestation. A total of 53 G. pallida samples (~1,042,000 individuals) were collected and analyzed, representing five different fields in Idaho, a greenhouse population, and a field in Scotland that was used for external comparison. According to genome-wide allele frequency and fixation index (Fst) analyses, most of the genetic variation was shared among the G. pallida populations in Idaho fields pre-fumigation, indicating that the infestation likely resulted from a single introduction. Temporal patterns of genome-wide polymorphisms involving (1) pre-fumigation field samples collected in 2007 and 2014 and (2) pre- and post-fumigation samples revealed nucleotide variants (SNPs, single-nucleotide polymorphisms) with significantly differentiated allele frequencies indicating genetic differentiation. This study provides insights into the genetic origins and adaptive potential of G. pallida invading new environments.

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