GeneWalk identifies relevant gene functions for a biological context using network representation learning, bioRxiv, 2019-09-05

AbstractThe primary bottleneck in high-throughput genomics experiments is identifying the most important genes and their relevant functions from a list of gene hits. Existing methods such as Gene Ontology (GO) enrichment analysis provide insight at the gene set level. For individual genes, GO annotations are static and biological context can only be added by manual literature searches. Here, we introduce GeneWalk (<jatsext-link xmlnsxlink=httpwww.w3.org1999xlink ext-link-type=uri xlinkhref=httpgithub.comchurchmanlabgenewalk>github.comchurchmanlabgenewalk<jatsext-link>), a method that identifies individual genes and their relevant functions under a particular experimental condition. After automatic assembly of an experiment-specific gene regulatory network, GeneWalk quantifies the similarity between vector representations of each gene and its GO annotations through representation learning, yielding annotation significance scores that reflect their functional relevance for the experimental context. We demonstrate the use of GeneWalk analysis of RNA-seq and nascent transcriptome (NET-seq) data from human cells and mouse brains, validating the methodology. By performing gene- and condition-specific functional analysis that converts a list of genes into data-driven hypotheses, GeneWalk accelerates the interpretation of high-throughput genetics experiments.

biorxiv bioinformatics 200-500-users 2019

A novel weight lifting task for investigating effort and persistence in rats, bioRxiv, 2019-09-04

AbstractHere we present a novel effort-based task for laboratory rats the weight lifting task (WLT). Studies of effort expenditure in rodents have typically involved climbing barriers within T-mazes or operant lever pressing paradigms. These task designs have been successful for neuropharmacological and neurophysiological investigations, but both tasks involve simple action patterns prone to automatization. Furthermore, high climbing barriers present risk of injury to animals andor tethered recording equipment. In the WLT, a rat is placed in a large rectangular arena and tasked with pulling a rope 30 cm to trigger food delivery at a nearby spout; weights can be added to the rope in 45 g increments to increase the intensity of effort. As compared to lever pressing and barrier jumping, 30 cm of rope pulling is a multi-step action sequence requiring sustained effort. The actions are carried out on the single plane of the arena floor, making it safer for the animal and more suitable for tethered equipment and video tracking. A microcontroller and associated sensors enable precise timestamping of specific behaviors to synchronize with electrophysiological recordings. The rope and reward spout are spatially segregated to allow for spatial discrimination of the effort zone and the reward zone. We validated the task across five cohorts of rats (total n=35) and report consistent behavioral metrics. The WLT is well-suited for neuropharmacological andor in vivo neurophysiological investigations surrounding effortful behaviors, particularly when wanting to probe different aspects of effort expenditure (intensity vs. duration).

biorxiv animal-behavior-and-cognition 200-500-users 2019

 

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