Exploring the RNA Gap for Improving Diagnostic Yield in Primary Immunodeficiencies
Challenges in diagnosing primary immunodeficiency are numerous and diverse, with current whole-exome and whole-genome sequencing approaches only able to reach a molecular diagnosis in 25–60% of cases. We assess these problems and discuss how RNA-focused analysis has expanded and improved in recent y...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-12-01
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| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2019.01204/full |
| _version_ | 1830300629657976832 |
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| author | Jed J. Lye Anthony Williams Anthony Williams Diana Baralle Diana Baralle |
| author_facet | Jed J. Lye Anthony Williams Anthony Williams Diana Baralle Diana Baralle |
| author_sort | Jed J. Lye |
| collection | DOAJ |
| description | Challenges in diagnosing primary immunodeficiency are numerous and diverse, with current whole-exome and whole-genome sequencing approaches only able to reach a molecular diagnosis in 25–60% of cases. We assess these problems and discuss how RNA-focused analysis has expanded and improved in recent years and may now be utilized to gain an unparalleled insight into cellular immunology. We review how investigation into RNA biology can give information regarding the differential expression, monoallelic expression, and alternative splicing—which have important roles in immune regulation and function. We show how this information can inform bioinformatic analysis pipelines and aid in the variant filtering process, expediting the identification of causal variants—especially those affecting splicing—and enhance overall diagnostic ability. We also demonstrate the challenges, which remain in the design of this type of investigation, regarding technological limitation and biological considerations and suggest potential directions for the clinical applications. |
| first_indexed | 2024-12-19T08:31:35Z |
| format | Article |
| id | doaj.art-085a2e7e20d944c5997f50030f7e736f |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-19T08:31:35Z |
| publishDate | 2019-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-085a2e7e20d944c5997f50030f7e736f2022-12-21T20:29:10ZengFrontiers Media S.A.Frontiers in Genetics1664-80212019-12-011010.3389/fgene.2019.01204495353Exploring the RNA Gap for Improving Diagnostic Yield in Primary ImmunodeficienciesJed J. Lye0Anthony Williams1Anthony Williams2Diana Baralle3Diana Baralle4University of Southampton Medical School, University of Southampton, Southampton, United KingdomUniversity of Southampton Medical School, University of Southampton, Southampton, United KingdomWessex Investigational Sciences Hub Laboratory (WISH Lab), Faculty of Medicine, University of Southampton, Southampton, United KingdomUniversity of Southampton Medical School, University of Southampton, Southampton, United KingdomFaculty of Medicine, Highfield Campus, University of Southampton, Southampton, United KingdomChallenges in diagnosing primary immunodeficiency are numerous and diverse, with current whole-exome and whole-genome sequencing approaches only able to reach a molecular diagnosis in 25–60% of cases. We assess these problems and discuss how RNA-focused analysis has expanded and improved in recent years and may now be utilized to gain an unparalleled insight into cellular immunology. We review how investigation into RNA biology can give information regarding the differential expression, monoallelic expression, and alternative splicing—which have important roles in immune regulation and function. We show how this information can inform bioinformatic analysis pipelines and aid in the variant filtering process, expediting the identification of causal variants—especially those affecting splicing—and enhance overall diagnostic ability. We also demonstrate the challenges, which remain in the design of this type of investigation, regarding technological limitation and biological considerations and suggest potential directions for the clinical applications.https://www.frontiersin.org/article/10.3389/fgene.2019.01204/fullprimary immunodeficiency disordersclinical diagnosticsRNASeqRNARNAseq analysis |
| spellingShingle | Jed J. Lye Anthony Williams Anthony Williams Diana Baralle Diana Baralle Exploring the RNA Gap for Improving Diagnostic Yield in Primary Immunodeficiencies Frontiers in Genetics primary immunodeficiency disorders clinical diagnostics RNASeq RNA RNAseq analysis |
| title | Exploring the RNA Gap for Improving Diagnostic Yield in Primary Immunodeficiencies |
| title_full | Exploring the RNA Gap for Improving Diagnostic Yield in Primary Immunodeficiencies |
| title_fullStr | Exploring the RNA Gap for Improving Diagnostic Yield in Primary Immunodeficiencies |
| title_full_unstemmed | Exploring the RNA Gap for Improving Diagnostic Yield in Primary Immunodeficiencies |
| title_short | Exploring the RNA Gap for Improving Diagnostic Yield in Primary Immunodeficiencies |
| title_sort | exploring the rna gap for improving diagnostic yield in primary immunodeficiencies |
| topic | primary immunodeficiency disorders clinical diagnostics RNASeq RNA RNAseq analysis |
| url | https://www.frontiersin.org/article/10.3389/fgene.2019.01204/full |
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