Bridging the functional gap by sinergy of exome/genome and RNA sequencing: A systematic semi-quantitative review mosting highent diagnostic rendize in genetic diagnostics
PediatriaResumo original em inglês
O que aconteceu
Although exome and/or genome sequencing (ES/GS) is highly effective in identifying pathogenic variants, they may not capture the functional consequences of variants. RNA sequencing (RNA-seq), when used alongside ES/GS, addresses this limitation.
A systematic semi-quantitative review that included 200 studies reporting ES/GS or that were followed by RNA-seq diagnostic rates from 2014 to 2024 was conducted.
O que encontraram
Although the weighted average diagnostic rate for ES/GS followed by RNA-seq was 0.44 (ranging from 0.34 to 0.53), studies with ES/GS alone reported a pooled diagnostic rate of 0.37 (95% CI: 0.35-0.39; P = .18). The subset of studies with ES/GS as the first-tier test followed by RNA-seq revealed a trend towards improved diagnostic yields with the addition of RNA-seq (odds ratio: 1.31, 95% CI: 1.08-1.58; P = .01). For participants undiagnosed by ES/GS, RNA-seq contributed an incremental diagnostic rate of 5.4% (95% CI: 0.006-0.60, P = .018), achieved through confirming or reclassifying candidate variants as pathogenic/likely pathogenic, and an additional diagnostic rate of 3.3% (95% CI: 0.021-0.088; P = .002) through discovering novel variants. Our results also highlight the advantages of tissue samples over blood samples in improving the diagnostic yield, particularly of RNA-seq, in which an additional 6.2% for confirming ES/GS-identified candidates (95% CI: 0.028-0.97; P < .001) and another addition of 6.2% for new variant discovery (95% CI: 0.025-0.099; P = .001) were found.
Por que isso importa
Our findings emphasize the synergistic value of hypothesis-driven and hypothesis-free approaches in transcriptomic data analysis. The integration of RNA-seq into ES/GS workflows has shown promise in improving the molecular diagnosis of genetic diseases.
Resumo publicado sob licença CC BY. A tradução para o português ainda não chegou a este estudo.
O estudo original
Bridging the functional gap by synergy of exome/genome and RNA sequencing: A systematic semi-quantitative review demonstrating enhanced diagnostic yield in genetic diagnostics
Desiree M S Tse, Wenshu Tang, Martin M C Chui, Cario W S Lo, Joe Lai, Annie T W Chu, Brian H Y Chung
Descritores MeSH
- Exome Sequencing
- Genetic Testing
- Sequence Analysis, RNA
- Genetic Diseases, Inborn
- High-Throughput Nucleotide Sequencing
- Exome
- Humans
- Genome, Human
Veja também
Estudos relacionados
- A meta-analysis of diagnostic yield and clinical utility of genome and exome sequencing in pediatric rare and undiagnosed genetic diseases
- A microcosting and cost consequence analysis from a randomized controlled trial comparing genome sequencing with exome sequencing for genetic diagnosis
- Diagnostic Yield of Genome Sequencing Versus Exome Sequencing in Pediatric Patients With Rare Phenotypes: A Systematic Review and Meta-Analysis
- Benefits and barriers to broad implementation of genomic sequencing in the NICU