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Current Genomics

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ISSN (Print): 1389-2029
ISSN (Online): 1875-5488

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Research Article

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

Author(s): Chandrashekar Karunakaran, Vidya Niranjan*, Anagha S. Setlur, Dhanya Pradeep and Jitendra Kumar*

Volume 25, Issue 1, 2024

Published on: 22 January, 2024

Page: [41 - 64] Pages: 24

DOI: 10.2174/0113892029285310231227105503

Price: $65

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.

Methods: 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.

Results: 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.

Keywords: Colorectal cancer, exome analysis, non-synonymous, deleterious mutations, mutational profiling, multi-dimensional genomics, CTSB, CPNE1.

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