Functional and regulatory aspects of oxidative stress response in X monosomy.

The partial/complete loss of one X chromosome in a human female leads to Turner syndrome (TS). TS individuals display a range of phenotypes including short stature, osteoporosis, ovarian malfunction, diabetes, and thyroid dysfunction. Epigenetic factors and regulatory networks are distinctly different in X monosomy (45, X). In a lifetime, an individual is exposed to a variety of stress conditions. To study whether X monosomy cells display a differential response upon exposure to mild stress as compared to normal 46, XX cells and whether this may contribute to various co-morbidities in aneuploid individuals, we have carried out a transcriptomic analysis of human fibroblasts 45, X and 46, XX after exposure to mild oxidative stress. Under these conditions, over 350 transcripts were seen to be differentially expressed in 45, X and 46, XX cells. Pathways associated with oxidative stress were differentially expressed highlighting the differential regulation of genes and associated phenotypes. It could be seen that X monosomy cells are more susceptible to oxidative stress as compared to normal cells and have altered molecular pathways both in normal conditions and also upon exposure to mild oxidative stress. To explore this aspect in detail, we have mapped the expressions of transcription factors (TFs) in 45, X and 46, XX cells. The network of transcription activating factors is differentially regulated in 45, X and 46, XX cells under stress exposure. It is tempting to speculate that the altered ability of 45, X (Turner) cells to respond to stress may play a significant role in the physiological function and altered phenotypes in Turner syndrome.

Construction, analysis and validation of co-expression network to understand stress adaptation in Deinococcus radiodurans R1.

Systems biology based approaches have been effectively utilized to mine high throughput data. In the current study, we have performed system-level analysis for Deinococcus radiodurans R1 by constructing a gene co-expression network based on several microarray datasets available in the public domain. This condition-independent network was constructed by Weighted Gene Co-expression Network Analysis (WGCNA) with 61 microarray samples from 9 different experimental conditions. We identified 13 co-expressed modules, of which, 11 showed functional enrichments of one or more pathway/s or biological process. Comparative analysis of differentially expressed genes and proteins from radiation and desiccation stress studies with our co-expressed modules revealed the association of cyan with radiation response. Interestingly, two modules viz darkgreen and tan was associated with radiation as well as desiccation stress responses. The functional analysis of these modules showed enrichment of pathways important for adaptation of radiation or desiccation stress. To decipher the regulatory roles of these stress responsive modules, we identified transcription factors (TFs) and then calculated a Biweight mid correlation between modules hub gene and the identified TFs. We obtained 7 TFs for radiation and desiccation responsive modules. The expressions of 3 TFs were validated in response to gamma radiation using qRT-PCR. Along with the TFs, selected close neighbor genes of two important TFs, viz., DR_0997 (CRP) and DR_2287 (AsnC family transcriptional regulator) in the darkgreen module were also validated. In our network, among 13 hub genes associated with 13 modules, the functionality of 5 hub genes which are annotated as hypothetical proteins (hypothetical hub genes) in D. radiodurans genome has been revealed. Overall the study provided a better insight of pathways and regulators associated with relevant DNA damaging stress response in D. radiodurans.

An exploration of microbial and associated functional diversity in the OMZ and non-OMZ areas in the Bay of Bengal.

Depletion of oxygen in certain marine areas creates oxygen minimum zones (OMZs), which can alter the species composition and abundance. We have carried out high-throughput 16S rRNA gene amplicon profiling from the Bay of Bengal (BOB) OMZ and non-OMZ areas. Typically, a total of 35 families of micro-organisms were identified as biomarkers for OMZ and non-OMZ regions in the BOB. Our analysis has identified families Pseudoalteromonadaceae, OM60 and Synechococcaceae to be abundant in oxygenated water, whereas organisms belonging to families Pelagibacteraceae and Caulobacteraceae, which are involved in sulphur and nitrogen metabolism, were prominent in the OMZ areas. Predictive functional analysis for these identified bacteria clearly that suggested an abundance of microbes with assimilatory sulphurreducing genes (cysl and csH) in the non-OMZ, while bacteria involved in dissimilatory sulphate reduction (known to carry aprA and aprB genes) were enriched in the OMZ areas. Comparative analysis with OMZ areas from Peru and Chile revealed that OMZ areas in the BOB are characterized by specific and distinctive bacterial diversity. Overall, the current analysis provides valuable documentation about the bacterial populations and their characteristics, which can generate pointers for their functional significance in the BOB.