Integrating multi-type aberrations from DNA and RNA through dynamic mapping gene space for subtype-specific breast cancer driver discovery

TL;DR

This paper presents a novel 'splicing-and-fusing' framework that integrates DNA and RNA aberration data using knowledge graphs and dynamic gene space mapping to identify subtype-specific breast cancer drivers.

Contribution

The study introduces a new framework combining knowledge graph and dynamic mapping techniques to effectively integrate multi-type aberrations for breast cancer driver discovery.

Findings

Effective integration of DNA and RNA aberrations achieved

Improved identification of subtype-specific breast cancer drivers

Framework outperforms existing methods in accuracy

Abstract

Driver event discovery is a crucial demand for breast cancer diagnosis and therapy. Especially, discovering subtype-specificity of drivers can prompt the personalized biomarker discovery and precision treatment of cancer patients. still, most of the existing computational driver discovery studies mainly exploit the information from DNA aberrations and gene interactions. Notably, cancer driver events would occur due to not only DNA aberrations but also RNA alternations, but integrating multi-type aberrations from both DNA and RNA is still a challenging task for breast cancer drivers. On the one hand, the data formats of different aberration types also differ from each other, known as data format incompatibility. One the other hand, different types of aberrations demonstrate distinct patterns across samples, known as aberration type heterogeneity. To promote the integrated analysis of subtype-specific breast cancer drivers, we design a "splicing-and-fusing" framework to address the issues of data format incompatibility and aberration type heterogeneity respectively. To overcome the data format incompatibility, the "splicing-step" employs a knowledge graph structure to connect multi-type aberrations from the DNA and RNA data into a unified formation. To tackle the aberration type heterogeneity, the "fusing-step" adopts a dynamic mapping gene space integration approach to represent the multi-type information by vectorized profiles. The experiments also demonstrate the advantages of our approach in both the integration of multi-type aberrations from DNA and RNA and the discovery of subtype-specific breast cancer drivers. In summary, our "splicing-and-fusing" framework with knowledge graph connection and dynamic mapping gene space fusion of multi-type aberrations data from DNA and RNA can successfully discover potential breast cancer drivers with subtype-specificity indication.