Shrestha, V. | Search bioRxiv

bioRxiv2020

HAPPI GWAS: Holistic Analysis with Pre and Post Integration GWAS

MotivationAdvanced publicly available sequencing data from large populations have enabled in-formative genome-wide association studies (GWAS) that associate SNPs with phenotypic traits of interest. Many publicly available tools able to perform GWAS have been developed in response to increased demand. However, these tools lack a comprehensive pipeline that includes both pre-GWAS analysis such as outlier removal, data transformation, and calculation of Best Linear Unbiased Predictions (BLUPs) or Best Linear Unbiased Estimates (BLUEs). In addition, post-GWAS analysis such as haploblock analysis and candidate gene identification are lacking. ResultsHere, we present HAPPI GWAS, an open-source GWAS tool able to perform pre-GWAS, GWAS, and post-GWAS analysis in an automated pipeline using the command-line interface. AvailabilityHAPPI GWAS is written in R for any Unix-like operating systems and is available on GitHub (https://github.com/Angelovici-Lab/HAPPI.GWAS.git). Contactangelovicir@missouri.edu

bioinformatics↗

bioRxiv2019

The thalamic basis of outcome and cognitive impairment in traumatic brain injury

ObjectiveTo understand how, biologically, the acute event of traumatic brain injury gives rise to a long-term disease, we address the relationship between evolving cortical and subcortical brain damage and measures of functional outcome and cognitive functioning at six months post-injury.\n\nMethodsLongitudinal analysis of clinical and MRI data collected, in a tertiary neurointensive care setting, in a continuous sample of 157 patients surviving moderate to severe traumatic brain injury between 2000 and 2018. For each patient we collected T1- and T2-weighted MRI data, acutely and at a six-months follow-up, as well as acute measures of injury severity (Glasgow Coma Scale) and follow-up measures of functional impairment (Glasgow Outcome Scale extended), and, in a subset of patients, neuropsychological measures of attention, executive functions, and episodic memory.\n\nResultsIn the final cohort of 113 subcortical and 92 cortical datasets that survived (blind) quality control, extensive atrophy was observed over the first six months post-injury across the brain. Nonetheless, only atrophy within subcortical regions, particularly in left thalamus, were associated with functional outcome and neuropsychological measures of attention, executive functions, and episodic memory. Furthermore, when brought together in an analytical model, longitudinal brain measurements could distinguish good versus bad outcome with 90% accuracy, whereas acute brain and clinical measurements alone could only achieve 20% accuracy.\n\nInterpretationDespite great injury heterogeneity, secondary thalamic pathology is a measurable minimum common denominator mechanism directly relating biology to clinical measures of outcome and cognitive functioning, potentially linking the acute \"event\" and the long(er)-term \"disease\" of TBI.

neuroscience↗