ssMutPA: single-sample mutation-based pathway analysis approach for cancer precision medicine.

IF 11.8 2区 生物学 Q1 MULTIDISCIPLINARY SCIENCES
Yalan He, Jiyin Lai, Qian Wang, Bingyue Pan, Siyuan Li, Xilong Zhao, Ziyi Wang, Yongbao Zhang, Yujie Tang, Junwei Han
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引用次数: 0

Abstract

Background: Single-sample pathway enrichment analysis is an effective approach for identifying cancer subtypes and pathway biomarkers, facilitating the development of precision medicine. However, the existing approaches focused on investigating the changes in gene expression levels but neglected somatic mutations, which play a crucial role in cancer development.

Findings: In this study, we proposed a novel single-sample mutation-based pathway analysis approach (ssMutPA) to infer individualized pathway activities by integrating somatic mutation data and the protein-protein interaction network. For each sample, ssMutPA first uses local and global weighted strategies to evaluate the effects of genes from mutations according to the network topology and then calculates a single-sample mutation-based pathway enrichment score (ssMutPES) to reflect the accumulated effect of mutations of each pathway. To illustrate the performance of ssMutPA, we applied it to 33 cancer cohorts from The Cancer Genome Atlas database and revealed patient stratification with significantly different prognosis in each cancer type based on the ssMutPES profiles. We also found that the identified characteristic pathways with high overlap across different cancers could be used as potential prognosis biomarkers. Moreover, we applied ssMutPA to 2 melanoma cohorts with immunotherapy and identified a subgroup of patients who may benefit from therapy.

Conclusions: We provided evidence that ssMutPA could infer mutation-based individualized pathway activity profiles and complement the current individualized pathway analysis approaches focused on gene expression data, which may offer the potential for the development of precision medicine. ssMutPA is available at https://CRAN.R-project.org/package=ssMutPA.

ssMutPA:基于单样本突变的癌症精准医学路径分析方法。
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来源期刊
GigaScience
GigaScience MULTIDISCIPLINARY SCIENCES-
CiteScore
15.50
自引率
1.10%
发文量
119
审稿时长
1 weeks
期刊介绍: GigaScience seeks to transform data dissemination and utilization in the life and biomedical sciences. As an online open-access open-data journal, it specializes in publishing "big-data" studies encompassing various fields. Its scope includes not only "omic" type data and the fields of high-throughput biology currently serviced by large public repositories, but also the growing range of more difficult-to-access data, such as imaging, neuroscience, ecology, cohort data, systems biology and other new types of large-scale shareable data.
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