Prioritization of non-coding disease-causing variants and long non-coding RNAs in liver cancer

  • Authors:
    • Hua Li
    • Zekun He
    • Yang Gu
    • Lin Fang
    • Xin Lv
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  • Published online on: September 14, 2016     https://doi.org/10.3892/ol.2016.5135
  • Pages: 3987-3994
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Abstract

There are multiple bioinformatics tools available for the detection of coding driver mutations in cancers. However, the prioritization of pathogenic non‑coding variants remains a challenging and demanding task. The present study was performed to discriminate non‑coding disease‑causing mutations and prioritize potential cancer‑implicated long non‑coding RNAs (lncRNAs) in liver cancer using a logistic regression model. A logistic regression model was constructed by combining 19,153 disease‑associated ClinVar and human gene mutation database pathogenic variants as the response variable and non‑coding features as the predictor variable. Genome‑wide association study (GWAS) disease or trait‑associated variants and recurrent somatic mutations were used to validate the model. Non‑coding gene features with the highest fractions of load were characterized and potential cancer‑associated lncRNA candidates were prioritized by combining the fraction of high‑scoring regions and average score predicted by the logistic regression model. H3K9me3 and conserved regions were the most negatively and positively informative for the model, respectively. The area under the receiver operating characteristic curve of the model was 0.92. The average score of GWAS disease‑associated variants was significantly increased compared with neutral single nucleotide polymorphisms (5.8642 vs. 5.4707; P<0.001), the average score of recurrent somatic mutations of liver cancer was significantly increased compared with non‑recurrent somatic mutations (5.4101 vs. 5.2768; P=0.0125). The present study found regions in lncRNAs and introns/untranslated regions of protein coding genes where mutations are most likely to be damaging. In total, 847 lncRNAs were filtered out from the background. Characterization of this subset of lncRNAs showed that these lncRNAs are more conservative, less mutated and more highly expressed compared with other control lncRNAs. In addition, 23 of these lncRNAs were differentially expressed between 12 pairs of liver cancer and adjacent normal specimens. The logistic regression model is a useful tool to prioritize non‑coding pathogenic variants and lncRNAs, and paves the way for the detection of non‑coding driver lncRNAs in liver cancer.
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November-2016
Volume 12 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Copy and paste a formatted citation
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Spandidos Publications style
Li H, He Z, Gu Y, Fang L and Lv X: Prioritization of non-coding disease-causing variants and long non-coding RNAs in liver cancer. Oncol Lett 12: 3987-3994, 2016
APA
Li, H., He, Z., Gu, Y., Fang, L., & Lv, X. (2016). Prioritization of non-coding disease-causing variants and long non-coding RNAs in liver cancer. Oncology Letters, 12, 3987-3994. https://doi.org/10.3892/ol.2016.5135
MLA
Li, H., He, Z., Gu, Y., Fang, L., Lv, X."Prioritization of non-coding disease-causing variants and long non-coding RNAs in liver cancer". Oncology Letters 12.5 (2016): 3987-3994.
Chicago
Li, H., He, Z., Gu, Y., Fang, L., Lv, X."Prioritization of non-coding disease-causing variants and long non-coding RNAs in liver cancer". Oncology Letters 12, no. 5 (2016): 3987-3994. https://doi.org/10.3892/ol.2016.5135