Integrative computational evaluation of genetic markers for Alzheimer's disease.

Recent studies have reported hundreds of genes linked to Alzheimer's Disease (AD). However, many of these candidate genes may be not identified in different studies when analyses were replicated. Moreover, results could be controversial. Here, we proposed a computational workflow to curate and evaluate AD related genes. The method integrates large scale literature knowledge data and gene expression data that were acquired from postmortem human brain regions (AD case/control: 31/32 and 22/8). Pathway Enrichment, Sub-Network Enrichment, and Gene-Gene Interaction analysis were conducted to study the pathogenic profile of the candidate genes, with 4 metrics proposed and validated for each gene. By using our approach, a scalable AD genetic database was developed, including AD related genes, pathways, diseases and info of supporting references. The AD case/control classification supported the effectiveness of the 4 proposed metrics, which successfully identified 21 well-studied AD genes (i.g. TGFB1, CTNNB1, APP, IL1B, PSEN1, PTGS2, IL6, VEGFA, SOD1, AKT1, CDK5, TNF, GSK3B, TP53, CCL2, BDNF, NGF, IGF1, SIRT1, AGER and TLR) and highlighted one recently reported AD gene (i.g. ITGB1). The computational biology approach and the AD database developed in this study provide a valuable resource which may facilitate the understanding of the AD genetic profile.

Survival analysis in Caucasian pulmonary adenocarcinoma patients based on differential targets between Caucasian and Asian population.

Ethnicity differences may contribute to the variety of overall survival in pulmonary adenocarcinoma, while the influence of ethnicity relevant somatic driver mutations (ERSDM) profile on Caucasian survival is not well investigated. In this study, we studied epidermal growth factor receptor (EGFR), tumor protein p53 (TP53), Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), and Serine/Threonine Kinase 11 (STK11) to construct the ERSDM profile. Those genes were selected as harboring somatic driver mutations with >10% prevalence and with different occurrence between Caucasian and Asian ethnicity. Clinical information and transcriptome sequencing of 173 Caucasian pulmonary adenocarcinoma patients with matched mutation data are retrieved from TCGA, Kaplan-Meier analyses and Cox proportional-hazards regression models are further used to analyze the effect of the ERSDM profile on overall survival. There is no significant correlation between single gene mutation and overall survival, while patients with less than two mutated genes have a better overall survival compared with those with at least two mutated genes (p = 0.034). All of these indicate that multiple mutations in the ERSDM profile may be a negative prognostic factor for overall survival in Caucasian pulmonary adenocarcinoma patients.

Integrative computational approach to evaluate risk genes for postmenopausal osteoporosis.

In recent years, numerous studies reported over a hundred of genes playing roles in the etiology of postmenopausal osteoporosis (PO). However, many of these candidate genes were lack of replication and results were not always consistent. Here, the authors proposed a computational workflow to curate and evaluate PO related genes. They integrate large-scale literature knowledge data and gene expression data (PO case/control: 10/10) for the marker evaluation. Pathway enrichment, sub-network enrichment, and gene-gene interaction analysis were conducted to study the pathogenic profile of the candidate genes, with four metrics proposed and validated for each gene. By using the authors' approach, a scalable PO genetic database was developed; including PO related genes, diseases, pathways, and the supporting references. The PO case/control classification supported the effectiveness of the four proposed metrics, which successfully identified eight well-studied top PO genes (e.g. TGFB1, IL6, IL1B, TNF, ESR2, IGF1, HIF1A, and COL1A1) and highlighted one recently reported PO genes (e.g. IFNG). The computational biology approach and the PO database developed in this study provide a valuable resource which may facilitate understanding the genetic profile of PO.

An Integrative Computational Approach to Evaluate Genetic Markers for Bipolar Disorder.

Studies to date have reported hundreds of genes connected to bipolar disorder (BP). However, many studies identifying candidate genes have lacked replication, and their results have, at times, been inconsistent with one another. This paper, therefore, offers a computational workflow that can curate and evaluate BP-related genetic data. Our method integrated large-scale literature data and gene expression data that were acquired from both postmortem human brain regions (BP case/control: 45/50) and peripheral blood mononuclear cells (BP case/control: 193/593). To assess the pathogenic profiles of candidate genes, we conducted Pathway Enrichment, Sub-Network Enrichment, and Gene-Gene Interaction analyses, with 4 metrics proposed and validated for each gene. Our approach developed a scalable BP genetic database (BP_GD), including BP related genes, drugs, pathways, diseases and supporting references. The 4 metrics successfully identified frequently-studied BP genes (e.g. GRIN2A, DRD1, DRD2, HTR2A, CACNA1C, TH, BDNF, SLC6A3, P2RX7, DRD3, and DRD4) and also highlighted several recently reported BP genes (e.g. GRIK5, GRM1 and CACNA1A). The computational biology approach and the BP database developed in this study could contribute to a better understanding of the current stage of BP genetic research and assist further studies in the field.

An Integrative Computational Approach to Evaluate Genetic Markers for Chronic Lymphocytic Leukemia.

Recent studies reported hundreds of genes linked to chronic lymphocytic leukemia (CLL). However, many of these candidate genes were lack of replication and results were not always consistent. Here, we proposed a computational workflow to curate and evaluate CLL-related genes. The method integrates large-scale literature knowledge data, gene expression data, and related pathways/network information for quantitative marker evaluation. Pathway Enrichment, Sub-Network Enrichment, and Gene-Gene Interaction analysis were conducted to study the pathogenic profile of the candidate genes, with four metrics proposed and validated for each gene. By using our approach, a scalable CLL genetic database was developed including CLL-related genes, pathways, diseases and information of supporting references. The CLL case/control classification supported the effectiveness of the four proposed metrics, which successfully identified nine well-studied CLL genes (i.e., TNF, BCL2, TP53, VEGFA, P2RX7, AKT1, SYK, IL4, and MDM2) and highlighted two newly reported CLL genes (i.e., PDGFRA and CSF1R). The computational biology approach and the CLL database developed in this study provide a valuable resource that may facilitate the understanding of the genetic profile of CLL.