Dataset Information

ASNEO: Identification of personalized alternative splicing based neoantigens with RNA-seq.

ABSTRACT: Cancer neoantigens have shown great potential in immunotherapy, while current software focuses on identifying neoantigens which are derived from SNVs, indels or gene fusions. Alternative splicing widely occurs in tumor samples and it has been proven to contribute to the generation of candidate neoantigens. Here we present ASNEO, which is an integrated computational pipeline for the identification of personalized Alternative Splicing based NEOantigens with RNA-seq. Our analyses showed that ASNEO could identify neopeptides which are presented by MHC I complex through mass spectrometry data validation. When ASNEO was applied to two immunotherapy-treated cohorts, we found that alternative splicing based neopeptides generally have a higher immune score than that of somatic neopeptides and alternative splicing based neopeptides could be a marker to predict patient survival pattern. Our identification of alternative splicing derived neopeptides would contribute to a more complete understanding of the tumor immune landscape. Prediction of patient-specific alternative splicing neopeptides has the potential to contribute to the development of personalized cancer vaccines.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC7425491 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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<i>ASNEO</i>: Identification of personalized alternative splicing based neoantigens with RNA-seq.

Zhang Zhanbing Z Zhou Chi C Tang Lihua L Gong Yukang Y Wei Zhiting Z Zhang Gongchen G Wang Feng F Liu Qi Q Yu Jing J

Aging 20200722 14

Cancer neoantigens have shown great potential in immunotherapy, while current software focuses on identifying neoantigens which are derived from SNVs, indels or gene fusions. Alternative splicing widely occurs in tumor samples and it has been proven to contribute to the generation of candidate neoantigens. Here we present <i>ASNEO</i>, which is an integrated computational pipeline for the identification of personalized Alternative Splicing based NEOantigens with RNA-seq. Our analyses showed that ...[more]

PMID: 32697765

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Project description:BackgroundAlternative splicing isoforms have been reported as a new and robust class of diagnostic biomarkers. Over 95% of human genes are estimated to be alternatively spliced as a powerful means of producing functionally diverse proteins from a single gene. The emergence of next-generation sequencing technologies, especially RNA-seq, provides novel insights into large-scale detection and analysis of alternative splicing at the transcriptional level. Advances in Proteomic Technologies such as liquid chromatography coupled tandem mass spectrometry (LC-MS/MS), have shown tremendous power for the parallel characterization of large amount of proteins in biological samples. Although poor correspondence has been generally found from previous qualitative comparative analysis between proteomics and microarray data, significantly higher degrees of correlation have been observed at the level of exon. Combining protein and RNA data by searching LC-MS/MS data against a customized protein database from RNA-Seq may produce a subset of alternatively spliced protein isoform candidates that have higher confidence.ResultsWe developed a bioinformatics workflow to discover alternative splicing biomarkers from LC-MS/MS using RNA-Seq. First, we retrieved high confident, novel alternative splicing biomarkers from the breast cancer RNA-Seq database. Then, we translated these sequences into in silico Isoform Junction Peptides, and created a customized alternative splicing database for MS searching. Lastly, we ran the Open Mass spectrometry Search Algorithm against the customized alternative splicing database with breast cancer plasma proteome. Twenty six alternative splicing biomarker peptides with one single intron event and one exon skipping event were identified. Further interpretation of biological pathways with our Integrated Pathway Analysis Database showed that these 26 peptides are associated with Cancer, Signaling, Metabolism, Regulation, Immune System and Hemostasis pathways, which are consistent with the 256 alternative splicing biomarkers from the RNA-Seq.ConclusionsThis paper presents a bioinformatics workflow for using RNA-seq data to discover novel alternative splicing biomarkers from the breast cancer proteome. As a complement to synthetic alternative splicing database technique for alternative splicing identification, this method combines the advantages of two platforms: mass spectrometry and next generation sequencing and can help identify potentially highly sample-specific alternative splicing isoform biomarkers at early-stage of cancer.

Dataset Information

ASNEO: Identification of personalized alternative splicing based neoantigens with RNA-seq.

Publications

<i>ASNEO</i>: Identification of personalized alternative splicing based neoantigens with RNA-seq.

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