Biology subjects

Massirer, K. B.

Publications and source records attributed to Massirer, K. B..

2 recordsLinked to original sources

bioRxiv2018

BioFeatureFinder: Flexible, unbiased analysis of biological characteristics associated with genomic regions

BioFeatureFinder is a novel algorithm which allows analyses of many biological genomic landmarks (including alternatively spliced exons, DNA/RNA-binding protein binding sites, and gene/transcript functional elements, nucleotide content, conservation, k-mers, secondary structure) to identify distinguishing features. BFF uses a flexible underlying model that combines classical statistical tests with Big Data machine-learning strategies. The model is created using thousands of biological characteristics (features) that are used to build a feature map and interpret category labels in genomic ranges. Our results show that BFF is a reliable platform for analyzing large-scale datasets. We evaluated the RNA binding feature map of 110 eCLIP-seq datasets and were able to recover several well-known features from the literature for RNA-binding proteins; we were also able to uncover novel associations. BioFeatureFinder is available at https://github.com/kbmlab/BioFeatureFinder/.

bioinformatics↗

bioRxiv2017

Structural characterization of human Vaccinia-Related Kinases (VRK) bound to small-molecule inhibitors identifies different P-loop conformations

The human genome encodes two active Vaccinia-related protein kinases (VRK), VRK1 and VRK2. These proteins have been implicated in a number of cellular processes and linked to a variety of tumors. However, understanding the cellular role of VRKs and establishing their potential use as targets for therapeutic intervention has been limited by the lack of tool compounds that can specifically modulate the activity of these kinases in cells. Here we identified BI-D1870, a dihydropteridine inhibitor of RSK kinases, as a promising starting point for the development of chemical probes targeting the active VRKs. We solved co-crystal structures of both VRK1 and VRK2 bound to BI-D1870 and of VRK1 bound to two broad-spectrum inhibitors. These structures revealed that both VRKs can adopt a P-loop folded conformation, which is stabilized by different mechanisms on each protein. Based on these structures, we suggest modifications to the dihydropteridine scaffold that can be explored to produce potent and specific inhibitors towards VRK1 and VRK2.

biochemistry↗