000041312 001__ 41312 000041312 005__ 20240305134724.0 000041312 0247_ $$2doi$$a10.6083/bpxhc41312 000041312 037__ $$aIR 000041312 041__ $$aeng 000041312 245__ $$aA novel computational framework for inferring the developmental and cellular origins of rare and congenital disorders using scRNA-seq data 000041312 260__ $$bOregon Health and Science University 000041312 269__ $$a2023-07-20 000041312 336__ $$aAbstract 000041312 520__ $$aDespite their devastating impacts on millions of people, most rare and congenital disorders remain poorly understood, leaving the patients with these disorders with no FDA-approved treatment.  To inform the development of treatments for these diseases, it is crucial that we understand their root cause.  Therefore, we propose the development of two novel computational pipelines to discover the cellular etiology of diseases.  Based on the well-supported observation that disorders with a shared phenotype arise from overlapping molecular processes, we hypothesize that these processes are, in many cases, localized to a small set of cell types at specific developmental stages.  For our first aim, we will design a novel computational pipeline to discover the cell types whose disrupted intrinsic processes putatively cause a specific phenotype of interest.  Our second aim will be devoted to the development of the first computational pipeline for uncovering the pairs of cell types whose disrupted communication initiates the phenotype.  In addition, our pipelines will be the first to offer insight into the putative developmental stages at which these cell types are impacted. A major challenge in studying rare and congenital disorders is the difficulty in collecting disease-specific data.  Our focus on shared phenotypes of disorders will eliminate any dependence on knowing the mutated gene for any one disorder, and our pipelines will be designed to use single-cell gene expression data from healthy tissues, eliminating the need to collect samples directly from patients.  Our project will provide the research community with a dedicated tool for uncovering the cellular etiology of diseases based on their shared molecular processes. 000041312 540__ $$fCC BY 000041312 542__ $$fIn copyright - joint owners 000041312 650__ $$aSystems Biology$$036214 000041312 650__ $$aRare Diseases$$034662 000041312 650__ $$aDevelopmental Biology$$028463 000041312 650__ $$aSingle-Cell Gene Expression Analysis$$013872 000041312 650__ $$aGenomics$$033016 000041312 650__ $$aMutation$$022555 000041312 6531_ $$ascrna-seq 000041312 6531_ $$acongenital disorders 000041312 6531_ $$afetal anomalies 000041312 6531_ $$aorphan disease 000041312 6531_ $$adata pipeline 000041312 6531_ $$arare disorders 000041312 691__ $$aSchool of Medicine$$041369 000041312 692__ $$aDepartment of Medical Informatics and Clinical Epidemiology$$041422 000041312 7001_ $$aSullivan, Jennifer$$uOregon Health and Science University$$041354 000041312 7001_ $$aAdey, Andrew$$uOregon Health and Science University$$041354 000041312 7001_ $$aSchweitzer, Ronen$$uOregon Health and Science University$$041354 000041312 7001_ $$aMcWeeney, Shannon$$uOregon Health and Science University$$041354 000041312 711__ $$aResearch Week$$uOregon Health and Science University$$d2023 000041312 7201_ $$7Personal 000041312 8564_ $$9c4ebc264-a4d2-47c5-99ae-79b13593a7a7$$s369511$$uhttps://digitalcollections.ohsu.edu/record/41312/files/ResearchWeek.2023.Sullivan.Jennifer.pdf 000041312 980__ $$aResearch Week 000041312 981__ $$aPublished$$b2023-07-20