Chacon, P. | Search bioRxiv

bioRxiv2020

Atomic-level evolutionary information improves protein-protein interface scoring

The crucial role of protein interactions and the difficulty in characterising them experimentally strongly motivates the development of computational approaches for structural prediction. Even when protein-protein docking samples correct models, current scoring functions struggle to discriminate them from incorrect decoys. The previous incorporation of conservation and coevolution information has shown promise for improving protein-protein scoring. Here, we present a novel strategy to integrate atomic-level evolutionary information into different types of scoring functions to improve their docking discrimination. We applied this general strategy to our residue-level statistical potential from InterEvScore and to two atomic-level scores, SOAP-PP and Rosetta interface score (ISC). Including evolutionary information from as few as ten homologous sequences improves the top 10 success rates of these individual scores by respectively 6.5, 6 and 13.5 percentage points, on a large benchmark of 752 docking cases. The best individual homology-enriched score reaches a top 10 success rate of 34.4%. A consensus approach based on the complementarity between different homology-enriched scores further increases the top 10 success rate to 40%. All data used for benchmarking and scoring results, as well as pipelining scripts, are available at http://biodev.cea.fr/interevol/interevdata/

bioinformatics↗

bioRxiv2020

Cognitive performance in children and adolescents at high-risk for obsessive-compulsive disorder

BackgroundCognitive performance has been studied in subclinical obsessive-compulsive (OC) adults and in adults relatives of OCD patients. Meanwhile, no study has been conducted with children under the same conditions. Across a sample with 49 participants, we investigated whether children and adolescents at high-risk (HR) for OCD (n=18) would present an impaired performance on neurocognitive domains compared to healthy controls (HC, n=31), especially in visuoconstructive ability, executive functions, and intellectual efficiency, functions previously associated with OCD. MethodsFor the HR group, we considered the first-degree children relatives of patients with OCD that present obsessive-compulsive symptoms (OCS), but do not meet diagnostic criteria for OCD. Child psychiatric diagnoses were assessed by the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-PL) by experienced and trained psychologists and OCS were measured by Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). ResultsAlthough we did not find differences in the domains previously hypothesized, a Multivariate Analysis of Variance (MANOVA) revealed impairments in processing speed in HR group (p =0.019; F=3.115), and a t-test identified a higher IQ discrepancy in HR group when compared to HC (p =0.030; t =-2.239), and a discrepancy in verbal and non-verbal abilities as in the memory and working memory tasks. ConclusionsOur results suggest that differences in motor and processing speed and in IQ discrepancy are already present and were identified in a non-clinical sample of HR subjects. Further studies should investigate neurocognitive domains as possible predictors of pediatric OCD.

neuroscience↗