In Computational and structural biotechnology journal
Alternative splicing (AS) events modulate certain pathways and phenotypic plasticity in cancer. Although previous studies have computationally analyzed splicing events, it is still a challenge to uncover biological functions induced by reliable AS events from tremendous candidates. To provide essential splicing event signatures to assess pathway regulation, we developed a database by collecting two datasets: (i) reported literature and (ii) cancer transcriptome profile. The former includes knowledge-based splicing signatures collected from 63,229 PubMed abstracts using natural language processing, extracted for 202 pathways. The latter is the machine learning-based splicing signatures identified from pan-cancer transcriptome for 16 cancer types and 42 pathways. We established six different learning models to classify pathway activities from splicing profiles as a learning dataset. Top-ranked AS events by learning model feature importance became the signature for each pathway. To validate our learning results, we performed evaluations by (i) performance metrics, (ii) differential AS sets acquired from external datasets, and (iii) our knowledge-based signatures. The area under the receiver operating characteristic values of the learning models did not exhibit any drastic difference. However, random-forest distinctly presented the best performance to compare with the AS sets identified from external datasets and our knowledge-based signatures. Therefore, we used the signatures obtained from the random-forest model. Our database provided the clinical characteristics of the AS signatures, including survival test, molecular subtype, and tumor microenvironment. The regulation by splicing factors was additionally investigated. Our database for developed signatures supported retrieval and visualization system.
Lee Kyubin, Hyung Daejin, Cho Soo Young, Yu Namhee, Hong Sewha, Kim Jihyun, Kim Sunshin, Han Ji-Youn, Park Charny
AS, Alternative splicing, AUCPR, the area under the precision-recall curve, AUROC, the area under the receiver operating characteristic, Alternative splicing, DAS, differential alternative splicing, Database, EMT, epithelial mesenchymal transition, Gene signature, ML, machine learning, Machine-learning, NER, named entity recognition, NLP, natural language process, PCA, principal component analysis, PSI, percent spliced in index, RF, random-forest, SF, splicing factor, TCGA, The Cancer Genome Atlas, Text-mining, Tumor transcriptome