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

Journal of Human Genetics volume 67, pages 739–742 (2022)Cite this article

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Abstract

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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Acknowledgements

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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Authors and Affiliations

  1. Department of Genomic Function and Diversity, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan

    Daiki Kato, Satomi Mitsuhashi & Yuta Kochi

  2. Daiichi Sankyo Co., Ltd., Tokyo, Japan

    Daiki Kato

  3. Center for Medical Genetics, Keio University School of Medicine, Minato, Japan

    Fuyuki Miya

  4. Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan

    Fuyuki Miya & Tatsuhiko Tsunoda

  5. Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Shinji Saitoh

  6. Department of Medical Genetics, Osaka Women’s and Children’s Hospital, Izumi, Osaka, Japan

    Nobuhiko Okamoto

  7. Laboratory for Medical Science Mathematics, Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan

    Tatsuhiko Tsunoda

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  1. Daiki Kato
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  2. Satomi Mitsuhashi
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  4. Shinji Saitoh
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  7. Yuta Kochi
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Corresponding author

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 67, 739–742 (2022). https://doi.org/10.1038/s10038-022-01071-8

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  • DOI: https://doi.org/10.1038/s10038-022-01071-8

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