CAGI 5 splicing challenge: Improved exon skipping and intron retention predictions with MMSplice

Cheng, Jun; Celik, Muhammed Hasan; Thi Yen Duong, Nguyen; Avsec, Ziga und Gagneur, Julien (2019): CAGI 5 splicing challenge: Improved exon skipping and intron retention predictions with MMSplice. In: Human Mutation, Bd. 40, Nr. 9: S. 1243-1251

Abstract

Pathogenic genetic variants often primarily affect splicing. However, it remains difficult to quantitatively predict whether and how genetic variants affect splicing. In 2018, the fifth edition of the Critical Assessment of Genome Interpretation proposed two splicing prediction challenges based on experimental perturbation assays: Vex-seq, assessing exon skipping, and MaPSy, assessing splicing efficiency. We developed a modular modeling framework, MMSplice, the performance of which was among the best on both challenges. Here we provide insights into the modeling assumptions of MMSplice and its individual modules. We furthermore illustrate how MMSplice can be applied in practice for individual genome interpretation, using the MMSplice VEP plugin and the Kipoi variant interpretation plugin, which are directly applicable to VCF files.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department Biochemie
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 1059-7794
• Sprache: Englisch