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North, K.

Publications and source records attributed to North, K..

2 recordsLinked to original sources

dms-view: Interactive visualization tool for deep mutational scanning data

Summary and PurposeThe high-throughput technique of deep mutational scanning (DMS) has recently made it possible to experimentally measure the effects of all amino-acid mutations to a protein (Fowler and Fields 2014). Over the past five years, this technique has been used to study dozens of different proteins (Esposito et al. 2019) and answer a variety of research questions. For example, DMS has been used for protein engineering (Wrenbeck, Faber, and Whitehead 2017), understanding the human immune response to viruses (Lee et al. 2019), and interpreting human variation in a clinical setting (Starita et al. 2017; Gelman et al. 2019). Accompanying this proliferation of DMS studies has been the development of software tools (Bloom 2015; Rubin et al. 2017) and databases (Esposito et al. 2019) for data analysis and sharing. However, for many purposes it is important to also integrate and visualize the DMS data in the context of other information, such as the 3-D protein structure or natural sequence-variation data. Here we describe dms-view (https://dms-view.github.io/), a flexible, web-based, interactive visualization tool for DMS data. dms-view is written in JavaScript and D3, and links site-level and mutation-level DMS data to a 3-D protein structure. The user can interactively select sites of interest to examine the DMS measurements in the context of the protein structure. dms-view tracks the input data and user selections in the URL, making it possible to save specific views of interactively generated visualizations to share with collaborators or to support a published study. Importantly, dms-view takes a flexible input data file so users can easily visualize their own DMS data in the context of protein structures of their choosing, and also incorporate additional information such amino-acid frequencies in natural alignments.

bioinformatics

VIP interneurons selectively enhance weak but behaviorally-relevant stimuli.

Vasoactive intestinal peptide-expressing (VIP) interneurons in cortex regulate feedback inhibition of pyramidal neurons through suppression of somatostatin-expressing (SST) interneurons and, reciprocally, SST neurons inhibit VIP neurons. Here, we show that VIP neurons in mouse primary visual cortex have complementary contrast tuning to SST neurons and respond synergistically to front-to-back visual motion and locomotion. Network modeling indicates that this VIP-SST mutual antagonism regulates the gain of cortex to achieve both sensitivity to behaviorally-relevant stimuli and network stability.

neuroscience