Stratification of co-evolving genomic groups using ranked phylogenetic profiles

<p>Abstract</p> <p>Background</p> <p>Previous methods of detecting the taxonomic origins of arbitrary sequence collections, with a significant impact to genome analysis and in particular metagenomics, have primarily focused on compositional features of genomes. The evolutionary patterns of phylogenetic distribution of genes or proteins, represented by phylogenetic profiles, provide an alternative approach for the detection of taxonomic origins, but typically suffer from low accuracy. Herein, we present <it>rank-BLAST</it>, a novel approach for the assignment of protein sequences into genomic groups of the same taxonomic origin, based on the ranking order of phylogenetic profiles of target genes or proteins across the reference database.</p> <p>Results</p> <p>The rank-BLAST approach is validated by computing the phylogenetic profiles of all sequences for five distinct microbial species of varying degrees of phylogenetic proximity, against a reference database of 243 fully sequenced genomes. The approach - a combination of sequence searches, statistical estimation and clustering - analyses the degree of sequence divergence between sets of protein sequences and allows the classification of protein sequences according to the species of origin with high accuracy, allowing taxonomic classification of 64% of the proteins studied. In most cases, a main cluster is detected, representing the corresponding species. Secondary, functionally distinct and species-specific clusters exhibit different patterns of phylogenetic distribution, thus flagging gene groups of interest. Detailed analyses of such cases are provided as examples.</p> <p>Conclusion</p> <p>Our results indicate that the rank-BLAST approach can capture the taxonomic origins of sequence collections in an accurate and efficient manner. The approach can be useful both for the analysis of genome evolution and the detection of species groups in metagenomics samples.</p

Sprouty4 Is an Endogenous Negative Modulator of TrkA Signaling and Neuronal Differentiation Induced by NGF

The Sprouty (Spry) family of proteins represents endogenous regulators of downstream signaling pathways induced by receptor tyrosine kinases (RTKs). Using real time PCR, we detect a significant increase in the expression of Spry4 mRNA in response to NGF, indicating that Spry4 could modulate intracellular signaling pathways and biological processes induced by NGF and its receptor TrkA. In this work, we demonstrate that overexpression of wild-type Spry4 causes a significant reduction in MAPK and Rac1 activation and neurite outgrowth induced by NGF. At molecular level, our findings indicate that ectopic expression of a mutated form of Spry4 (Y53A), in which a conserved tyrosine residue was replaced, fail to block both TrkA-mediated Erk/MAPK activation and neurite outgrowth induced by NGF, suggesting that an intact tyrosine 53 site is required for the inhibitory effect of Spry4 on NGF signaling. Downregulation of Spry4 using small interference RNA knockdown experiments potentiates PC12 cell differentiation and MAPK activation in response to NGF. Together, these findings establish a new physiological mechanism through which Spry4 regulates neurite outgrowth reducing not only the MAPK pathway but also restricting Rac1 activation in response to NGF

The influence of vibration on seated human drowsiness.

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