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Utility of tissue-specific gene expression scores for gene prioritization in Mendelian diseases


In genetic testing of Mendelian diseases, it is a bioinformatics challenge to effectively prioritize disease-causing candidate genes listed from massively parallel sequencing. Tissue specificity of the gene expression levels may give a clue because it may reflect tissue-specific disease manifestation. However, considering poor correlations between mRNA and protein expression in some genes, it is not clear whether transcriptomics- or proteomics-based tissue specificity should be used to prioritize candidate genes. Therefore, we compared the efficiency of tissue-specific scores (TS scores) obtained from transcriptome and proteome data in prioritizing candidate genes for whole exome sequencing (WES) analysis of Mendelian disease patients. We show that both Protein and RNA TS scores are useful in prioritizing candidate genes in WES analysis, although diseases like coagulopathies get more benefit from Protein TS score. This study may provide useful evidence in developing new methods to effectively identify novel disease-causing genes.

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We are thankful to the patients and their families for their participation in this study. This work was supported by a grant from Medical Research Center Initiative for High Depth Omics.

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Correspondence to Yuta Kochi.

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DK is an employee of Daiichi Sankyo Co., Ltd. The other authors declare no competing interests.

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Kato, D., Mitsuhashi, S., Miya, F. et al. Utility of tissue-specific gene expression scores for gene prioritization in Mendelian diseases. J Hum Genet (2022).

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