Exploring the Role of Non-synonymous and Deleterious Variants Identified in Colorectal Cancer: A Multi-dimensional Computational Scrutiny of Exomes

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-01-23 DOI:10.2174/0113892029285310231227105503

K Chandrashekar, Vidya Niranjan, Anagha S Setlur, Dhanya Pradeep, Jitendra Kumar

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引用次数: 0

Abstract

Introduction:: Colorectal cancers are the world’s third most commonly diagnosed type of cancer. Currently, there are several diagnostic and treatment options to combat it. However, a delay in detection of the disease is life-threatening. Additionally, a thorough analysis of the exomes of cancers reveals potential variation data that can be used for early disease prognosis. Method:: By utilizing a comprehensive computational investigation, the present study aimed to reveal mutations that could potentially predispose to colorectal cancer. Ten colorectal cancer exomes were retrieved. Quality control assessments were performed using FastQC and MultiQC, gapped alignment to the human reference genome (hg19) using Bowtie2 and calling the germline variants using Haplotype caller in the GATK pipeline. The variants were filtered and annotated using SIFT and PolyPhen2 successfully categorized the mutations into synonymous, non-synonymous, start loss and stop gain mutations as well as marked them as possibly damaging, probably damaging and benign. This mutational profile helped in shortlisting frequently occurring mutations and associated genes, for which the downstream multi-dimensional expression analyses were carried out. Result:: Our work involved prioritizing the non-synonymous, deleterious SNPs since these polymorphisms bring about a functional alteration to the phenotype. The top variations associated with their genes with the highest frequency of occurrence included LGALS8, CTSB, RAD17, CPNE1, OPRM1, SEMA4D, MUC4, PDE4DIP, ELN and ADRA1A. An in-depth multi-dimensional downstream analysis of all these genes in terms of gene expression profiling and analysis and differential gene expression with regard to various cancer types revealed CTSB and CPNE1 as highly expressed and overregulated genes in colorectal cancer. Conclusion:: Our work provides insights into the various alterations that might possibly lead to colorectal cancer and suggests the possibility of utilizing the most important genes identified for wetlab experimentation.

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探索在结直肠癌中发现的非同义变异和致死变异的作用：外显子组的多维计算审查

导言结直肠癌是世界上第三大最常诊断出的癌症类型。目前，有多种诊断和治疗方法可与之抗衡。然而，如果不能及时发现疾病，就会危及生命。此外，对癌症外显子组的全面分析揭示了潜在的变异数据，可用于疾病的早期预后。方法：本研究旨在通过全面的计算调查，揭示可能导致结直肠癌的潜在变异。研究人员检索了 10 个结直肠癌外显子组。使用 FastQC 和 MultiQC 进行质量控制评估，使用 Bowtie2 与人类参考基因组（hg19）进行间隙配对，并使用 GATK 管道中的 Haplotype caller 调用种系变异。使用 SIFT 和 PolyPhen2 对变异进行了过滤和注释，成功地将变异分为同义变异、非同义变异、起始丢失变异和终止增益变异，并将其标记为可能损伤性变异、可能损伤性变异和良性变异。这种突变特征有助于筛选出频繁发生的突变和相关基因，并对其进行下游多维度表达分析。结果我们的工作包括优先考虑非同义、有害的 SNP，因为这些多态性会导致表型的功能性改变。出现频率最高的变异基因包括 LGALS8、CTSB、RAD17、CPNE1、OPRM1、SEMA4D、MUC4、PDE4DIP、ELN 和 ADRA1A。通过对所有这些基因的基因表达谱进行深入的多维下游分析，以及对不同癌症类型的差异基因表达进行分析，发现 CTSB 和 CPNE1 是结直肠癌中高表达和高调的基因。结论我们的工作使我们对可能导致结直肠癌的各种改变有了更深入的了解，并提出了利用已确定的最重要基因进行湿实验室实验的可能性。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.