Analysis of genomic and transcriptomic variations as prognostic signature for lung adenocarcinoma.

BACKGROUND: Lung cancer is the leading cause of the largest number of deaths worldwide and lung adenocarcinoma is the most common form of lung cancer. In order to understand the molecular basis of lung adenocarcinoma, integrative analysis have been performed by using genomics, transcriptomics, epigenomics, proteomics and clinical data. Besides, molecular prognostic signatures have been generated for lung adenocarcinoma by using gene expression levels in tumor samples. However, we need signatures including different types of molecular data, even cohort or patient-based biomarkers which are the candidates of molecular targeting. RESULTS: We built an R pipeline to carry out an integrated meta-analysis of the genomic alterations including single-nucleotide variations and the copy number variations, transcriptomics variations through RNA-seq and clinical data of patients with lung adenocarcinoma in The Cancer Genome Atlas project. We integrated significant genes including single-nucleotide variations or the copy number variations, differentially expressed genes and those in active subnetworks to construct a prognosis signature. Cox proportional hazards model with Lasso penalty and LOOCV was used to identify best gene signature among different gene categories. We determined a 12-gene signature (BCHE, CCNA1, CYP24A1, DEPTOR, MASP2, MGLL, MYO1A, PODXL2, RAPGEF3, SGK2, TNNI2, ZBTB16) for prognostic risk prediction based on overall survival time of the patients with lung adenocarcinoma. The patients in both training and test data were clustered into high-risk and low-risk groups by using risk scores of the patients calculated based on selected gene signature. The overall survival probability of these risk groups was highly significantly different for both training and test datasets. CONCLUSIONS: This 12-gene signature could predict the prognostic risk of the patients with lung adenocarcinoma in TCGA and they are potential predictors for the survival-based risk clustering of the patients with lung adenocarcinoma. These genes can be used to cluster patients based on molecular nature and the best candidates of drugs for the patient clusters can be proposed. These genes also have a high potential for targeted cancer therapy of patients with lung adenocarcinoma.

A Comprehensive Survey of Tools and Software for Active Subnetwork Identification.

A recent focus of computational biology has been to integrate the complementary information available in molecular profiles as well as in multiple network databases in order to identify connected regions that show significant changes under different conditions. This allows for capturing dynamic and condition-specific mechanisms of the underlying phenomena and disease stages. Here we review 22 such integrative approaches for active module identification published over the last decade. This article only focuses on tools that are currently available for use and are well-maintained. We compare these methods focusing on their primary features, integrative abilities, network structures, mathematical models, and implementations. We also provide real-world scenarios in which these methods have been successfully applied, as well as highlight outstanding challenges in the field that remain to be addressed. The main objective of this review is to help potential users and researchers to choose the best method that is suitable for their data and analysis purpose.