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Genome-wide transcriptomics and copy number profiling identify patient-specific CNV-lncRNA-mRNA regulatory triplets in colorectal cancer
Journal article   Open access   Peer reviewed

Genome-wide transcriptomics and copy number profiling identify patient-specific CNV-lncRNA-mRNA regulatory triplets in colorectal cancer

Tianqi Liu, Yining Liu, Xiangqian Su, Lin Peng, Jiangbo Chen, Pu Xing, Xiaowen Qiao, Zaozao Wang, Jiabo Di, Min Zhao, …
Computers in Biology and Medicine, Vol.153, pp.1-13
2023
DOI: https://doi.org/10.1016/j.compbiomed.2023.106545
PMID: 36646024
Appears in  Cancer Research Cluster Research Collection
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Genome-wide transcriptomics and copy number profiling identify patient-specific CNV-lncRNA-mRNA regulatory triplets in colorectal cancer9.94 MBDownloadView
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https://doi.org/10.1016/j.compbiomed.2023.106545View
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Abstract

Colorectal cancer Copy number variation Dosage effect Long non-coding RNA Multi-omics data integration
Screening cancer genomes has provided an in depth characterization of genetic variants such as copy number variations (CNVs) and gene expression changes of non coding transcripts. Single dimensional experiments are often designed to differentiate a patient cohort into various sets with the aim of identifying molecular changes among groups; however, this may be inadequate to decipher the causal relationship between molecular signatures in individual patients. To overcome this challenge with respect to personalized medicine, we implemented a patient specific multi dimensional integrative approach to uncover coherent signals from multiple independent platforms. In particular, we focused on the consistent gene dosage effects of CNVs for both mRNA and long non coding RNA (lncRNA) expression in nine colorectal cancer patients. We identified 511 CNV lncRNA mRNA regulatory triplets associated with CNVs and aberrant expression of both mRNAs and lncRNAs. By filtering out inconsistent changes among CNVs, mRNAs, and lncRNAs, we further characterized 165 coherent motifs associated with 56 genes. In total, 108 motifs were linked with 31 copy number gains, 44 upregulated lncRNAs, and 45 upregulated mRNAs. Another 57 coherent downregulated motifs were also collected. We discuss how for many of these CNV lncRNA mRNA regulatory triplets, their clinical impact remains to be explored, including survival time, microsatellite instability, tumor stage, and primary tumor sites. By validating two example CNV lncRNA mRNA triplets with up and down regulation, we confirmed that individual variations in multiple dimensions are a robust tool to identify reliable molecular signals for personalized medicine. In summary, we utilized a patient specific computational pipeline to explore the consistent CNV driven motifs consisting of lncRNAs and mRNAs. We also identified LSM14B as a potential promoter in colorectal cancer progression, suggesting that it may serve as a target for colorectal cancer treatment.

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Biology
Computer Science, Interdisciplinary Applications
Engineering, Biomedical
Mathematical & Computational Biology

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