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Direct inference and control of genetic population structure from RNA sequencing data

Title: Direct inference and control of genetic population structure from RNA sequencing data
Authors: Fachrul, M; Karkey, A; Shakya, M; Judd, LM; Harshegyi, T; Sim, KS; Tonks, S; Dongol, S; Shrestha, R; Salim, A; Adhikari, A; Banda, HC; Blohmke, C; Darton, TC; Farooq, Y; Ghimire, M; Hill, J; Hoang, NT; Jere, TM; Kamzati, M; Kao, YH; Masesa, C; Mbewe, M; Msuku, H; Munthali, P; Nga, TVT; Nkhata, R; Saad, NJ; Van Tan, T; Thindwa, D; Khanam, F; Meiring, J; Clemens, JD; Dougan, G; Pitzer, VE; Qadri, F; Heyderman, RS; Gordon, MA; Voysey, M; Baker, S; Pollard, AJ; Khor, CC; Dolecek, C; Basnyat, B; Dunstan, SJ; Holt, KE; Inouye, M
Source: Communications Biology , 6 , Article 804. (2023)
Publisher Information: Springer Science and Business Media LLC
Publication Year: 2023
Collection: University College London: UCL Discovery
Subject Terms: Computational biology and bioinformatics; High-throughput screening; Software
Description: RNAseq data can be used to infer genetic variants, yet its use for estimating genetic population structure remains underexplored. Here, we construct a freely available computational tool (RGStraP) to estimate RNAseq-based genetic principal components (RG-PCs) and assess whether RG-PCs can be used to control for population structure in gene expression analyses. Using whole blood samples from understudied Nepalese populations and the Geuvadis study, we show that RG-PCs had comparable results to paired array-based genotypes, with high genotype concordance and high correlations of genetic principal components, capturing subpopulations within the dataset. In differential gene expression analysis, we found that inclusion of RG-PCs as covariates reduced test statistic inflation. Our paper demonstrates that genetic population structure can be directly inferred and controlled for using RNAseq data, thus facilitating improved retrospective and future analyses of transcriptomic data.
Document Type: article in journal/newspaper
File Description: text
Language: English
Relation: https://discovery.ucl.ac.uk/id/eprint/10175989/
Availability: https://discovery.ucl.ac.uk/id/eprint/10175989/1/s42003-023-05171-9.pdf; https://discovery.ucl.ac.uk/id/eprint/10175989/
Rights: open
Accession Number: edsbas.AEAB410F
Database: BASE