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Integrative genomics with mediation analysis in a survival context
Szilárd Nemes1, Toshima Z Parris2, Anna Danielsson2
1Division of Clinical Cancer Epidemiology, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden ; Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Computational and Mathematical Methods in Medicine
|January 24, 2014
Summary
This study introduces a new survival analysis framework to link DNA copy number aberrations (DCNA) and mRNA levels to patient outcomes. The method helps understand how genetic changes impact cancer survival through gene expression.
Area of Science:
- Genomics
- Cancer Research
- Biostatistics
Background:
- DNA copy number aberrations (DCNA) and altered gene expression are crucial in cancer development and patient mortality.
- Current integrative genomic analyses often neglect the critical factor of patient survival time.
Purpose of the Study:
- To propose a survival analysis-based framework for integrating DCNA and mRNA data.
- To test the hypothesis that DCNA affects patient survival through mediated mRNA levels.
- To provide a feasible method for analyzing the DCNA-mRNA-survival pathway.
Main Methods:
- Development of a survival analysis framework for integrative genomic data.
- Statistical inference algorithms for mediation analysis based on asymptotic results.
- Application to a breast cancer dataset (141 invasive tumors).
Main Results:
- The proposed framework enables the investigation of the DCNA-mRNA-survival pathway.
- Demonstrated applicability in a real-world breast cancer data analysis.
- Provided R implementation for practical use.
Conclusions:
- The survival analysis framework offers a novel approach to integrative genomics.
- This method enhances understanding of how genetic alterations influence cancer patient outcomes.
- Facilitates discovery of biomarkers and therapeutic targets by linking genomic changes to survival.
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