Systems view of adipogenesis via novel omics-driven and tissue-specific activity scoring of network functional modules

The investigation of the complex processes involved in cellular differentiation must be based on unbiased, high throughput data processing methods to identify relevant biological pathways. A number of bioinformatics tools are available that can generate lists of pathways ranked by statistical significance (i.e. by p-value), while ideally it would be desirable to functionally score the pathways relative to each other or to other interacting parts of the system or process. We describe a new computational method (Network Activity Score Finder - NASFinder) to identify tissue-specific, omicsdetermined sub-networks and the connections with their upstream regulator receptors to obtain a systems view of the differentiation of human adipocytes. Adipogenesis of human SBGS pre-adipocyte cells in vitro was monitored with a transcriptomic data set comprising six time points (0, 6, 48, 96, 192, 384 hours). To elucidate the mechanisms of adipogenesis, NASFinder was used to perform time-point analysis by comparing each time point against the control (0 h) and time-lapse analysis by comparing each time point with the previous one. NASFinder identified the coordinated activity of seemingly unrelated processes between each comparison, providing the first systems view of adipogenesis in culture. NASFinder has been implemented into a web-based, freely available resource associated with novel, easy to read visualization of omics data sets and network modules

Transcriptional changes in Teladorsagia circumcincta upon encountering host tissue of differing immune status

SUMMARYThe aim of this study was to elucidate transcriptional changes in the parasitic nematodeTeladorsagia circumcinctaupon encountering either naïve or immune ovine hosts. Pools of 100 000 exsheathed 3rd- stageT. circumcinctalarvae were exposedin vitroto either an immune or naïve ovine abomasal environment, RNA was extracted from the larvae and sequenced using the Roche 454 platform. Each sample produced approximately 82 000 reads that assembled to give approximately 5500 Isotigs (contigs). The two sequence datasets were clustered together to give a total of 6969 clusters of which 18 were differentially expressed (P&lt;0·001) between the two groups. Clusters with a predominance of reads in larvae exposed to the immune abomasal environment encoded homologues of peptidyl-glycine alpha-amidating monooxygenase, heat shock-protein 16-2 and IDA-1, a tyrosine phosphatase-like receptor protein. Clusters with a predominance of reads in the naïve environment encoded homologues of cytochrome b, EGg Laying defective family member 21 and NADH dehydrogenase subunit 5. Gene ontology analyses indicated that larvae exposed to the immune environment showed an increase in expression of genes involved in ‘carbon utilization’, ‘response to stimulus’ and ‘developmental process’. These data suggest thatT. circumcinctamodulates gene expression in response to the immune status of the host.</jats:p