Network based analysis of microarray gene expression profiles in response to electroacupuncture.

Electroacupuncture (EA) has been extensively considered as a tool for treating diseases and relieving various pains. However, understanding the molecular mechanisms underlying its effect is of high importance. In this study, we performed a weighted gene co-expression network analysis (WGCNA) on data collected from a microarray experiment to investigate the relationship underlying EA within three factors, time, frequency and tissue regions (periaqueductal grey (PAG) and spinal dorsal horn (DH)) as well as the biological implication of gene expression changes. Gene expression on rats in PAG-DH regions induced by EA with 2 Hz and 100 Hz at l h and 24 h were measured using microarray technology. The WGCNA was performed to identify distinct network modules related to EA effects. To find the biological function of genes and pathways, the gene ontology (GO) Consortium was applied and the gene-gene interaction network of top genes in important modules was visualized. We identified one network module (466 genes) which is significantly associated with time, another module (402 genes) significantly related to frequency, and three modules each consisting of 1144, 402 and 3148 genes that are significantly associated with tissue regions. Furthermore, meaningful biological pathways were enriched in association with each of the experimental factors during EA stimulation. Our analysis showed the robustness of WGCNA and revealed important genes within specific modules and pathways which might be activated in response to EA analgesia. The findings may help to clarify the underlying mechanisms of EA and provide references for future verification of this study.

Comprehensive analysis of high-throughput screens with HiTSeekR.

High-throughput screening (HTS) is an indispensable tool for drug (target) discovery that currently lacks user-friendly software tools for the robust identification of putative hits from HTS experiments and for the interpretation of these findings in the context of systems biology. We developed HiTSeekR as a one-stop solution for chemical compound screens, siRNA knock-down and CRISPR/Cas9 knock-out screens, as well as microRNA inhibitor and -mimics screens. We chose three use cases that demonstrate the potential of HiTSeekR to fully exploit HTS screening data in quite heterogeneous contexts to generate novel hypotheses for follow-up experiments: (i) a genome-wide RNAi screen to uncover modulators of TNFα, (ii) a combined siRNA and miRNA mimics screen on vorinostat resistance and (iii) a small compound screen on KRAS synthetic lethality. HiTSeekR is publicly available at http://hitseekr.compbio.sdu.dk It is the first approach to close the gap between raw data processing, network enrichment and wet lab target generation for various HTS screen types.

GxE interactions between FOXO genotypes and drinking tea are significantly associated with prevention of cognitive decline in advanced age in China.

Logistic regression analysis based on data from 822 Han Chinese oldest old aged 92+ demonstrated that interactions between carrying FOXO1A-266 or FOXO3-310 or FOXO3-292 and tea drinking at around age 60 or at present time were significantly associated with lower risk of cognitive disability at advanced ages. Associations between tea drinking and reduced cognitive disability were much stronger among carriers of the genotypes of FOXO1A-266 or FOXO3-310 or FOXO3-292 compared with noncarriers, and it was reconfirmed by analysis of three-way interactions across FOXO genotypes, tea drinking at around age 60, and at present time. Based on prior findings from animal and human cell models, we postulate that intake of tea compounds may activate FOXO gene expression, which in turn may positively affect cognitive function in the oldest old population. Our empirical findings imply that the health benefits of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles.