Reanalysis of exome sequencing data of intellectual disability samples

Yields and benefits

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Recently, with the advancement in next generation sequencing (NGS) along with the improvement of bioinformatics tools, whole exome sequencing (WES) has become the most efficient diagnostic test for patients with intellectual disability (ID). This study aims to estimate the yield of a reanalysis of ID negative exome cases after data reannotation. Total of 50 data files of exome sequencing, representing 50 samples were collected. The inclusion criteria include ID phenotype, and previous analysis indicated a negative result (no abnormality detected). These files were pre-processed and reannotated using ANNOVAR tool. Prioritized variants in the 50 cases studied were classified into three groups, (1) disease-causative variants (2) possible disease-causing variants and (3) variants in novel genes. Reanalysis resulted in the identification of pathogenic/likely pathogenic variants in six cases (12%). Thirteen cases (26%) were classified as having possible disease-causing variants. Candidate genes requiring future functional studies were detected in seven cases (14%). Improvement in bioinformatics tools, update in the genetic databases and literature, and patients' clinical phenotype update were the main reasons for identification of these variants in this study.

Original languageEnglish
JournalClinical Genetics
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Exome
Intellectual Disability
Computational Biology
Genetic Databases
Phenotype
Information Storage and Retrieval
Routine Diagnostic Tests
Genes

Keywords

  • diagnostic yield
  • DNAH14
  • DRG1
  • ID
  • LIN7B
  • RIC3
  • SYCL2
  • variant interpretation
  • whole-exome sequencing

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

@article{fe75b505d34643fb895f4e27afc31b65,
title = "Reanalysis of exome sequencing data of intellectual disability samples: Yields and benefits",
abstract = "Recently, with the advancement in next generation sequencing (NGS) along with the improvement of bioinformatics tools, whole exome sequencing (WES) has become the most efficient diagnostic test for patients with intellectual disability (ID). This study aims to estimate the yield of a reanalysis of ID negative exome cases after data reannotation. Total of 50 data files of exome sequencing, representing 50 samples were collected. The inclusion criteria include ID phenotype, and previous analysis indicated a negative result (no abnormality detected). These files were pre-processed and reannotated using ANNOVAR tool. Prioritized variants in the 50 cases studied were classified into three groups, (1) disease-causative variants (2) possible disease-causing variants and (3) variants in novel genes. Reanalysis resulted in the identification of pathogenic/likely pathogenic variants in six cases (12{\%}). Thirteen cases (26{\%}) were classified as having possible disease-causing variants. Candidate genes requiring future functional studies were detected in seven cases (14{\%}). Improvement in bioinformatics tools, update in the genetic databases and literature, and patients' clinical phenotype update were the main reasons for identification of these variants in this study.",
keywords = "diagnostic yield, DNAH14, DRG1, ID, LIN7B, RIC3, SYCL2, variant interpretation, whole-exome sequencing",
author = "Maryam Al-Nabhani and Samiya Al-Rashdi and Fathiya AL-Murshedi and Adila AlKindi and Khalid Al-Thihli and Abeer Al-Saegh and Amna AL-Fataisi and Watfa AL-Moamari and {AL Zadjali}, Fahad and Almundher Al-Maawali",
year = "2018",
month = "1",
day = "1",
doi = "10.1111/cge.13438",
language = "English",
journal = "Clinical Genetics",
issn = "0009-9163",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Reanalysis of exome sequencing data of intellectual disability samples

T2 - Yields and benefits

AU - Al-Nabhani, Maryam

AU - Al-Rashdi, Samiya

AU - AL-Murshedi, Fathiya

AU - AlKindi, Adila

AU - Al-Thihli, Khalid

AU - Al-Saegh, Abeer

AU - AL-Fataisi, Amna

AU - AL-Moamari, Watfa

AU - AL Zadjali, Fahad

AU - Al-Maawali, Almundher

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Recently, with the advancement in next generation sequencing (NGS) along with the improvement of bioinformatics tools, whole exome sequencing (WES) has become the most efficient diagnostic test for patients with intellectual disability (ID). This study aims to estimate the yield of a reanalysis of ID negative exome cases after data reannotation. Total of 50 data files of exome sequencing, representing 50 samples were collected. The inclusion criteria include ID phenotype, and previous analysis indicated a negative result (no abnormality detected). These files were pre-processed and reannotated using ANNOVAR tool. Prioritized variants in the 50 cases studied were classified into three groups, (1) disease-causative variants (2) possible disease-causing variants and (3) variants in novel genes. Reanalysis resulted in the identification of pathogenic/likely pathogenic variants in six cases (12%). Thirteen cases (26%) were classified as having possible disease-causing variants. Candidate genes requiring future functional studies were detected in seven cases (14%). Improvement in bioinformatics tools, update in the genetic databases and literature, and patients' clinical phenotype update were the main reasons for identification of these variants in this study.

AB - Recently, with the advancement in next generation sequencing (NGS) along with the improvement of bioinformatics tools, whole exome sequencing (WES) has become the most efficient diagnostic test for patients with intellectual disability (ID). This study aims to estimate the yield of a reanalysis of ID negative exome cases after data reannotation. Total of 50 data files of exome sequencing, representing 50 samples were collected. The inclusion criteria include ID phenotype, and previous analysis indicated a negative result (no abnormality detected). These files were pre-processed and reannotated using ANNOVAR tool. Prioritized variants in the 50 cases studied were classified into three groups, (1) disease-causative variants (2) possible disease-causing variants and (3) variants in novel genes. Reanalysis resulted in the identification of pathogenic/likely pathogenic variants in six cases (12%). Thirteen cases (26%) were classified as having possible disease-causing variants. Candidate genes requiring future functional studies were detected in seven cases (14%). Improvement in bioinformatics tools, update in the genetic databases and literature, and patients' clinical phenotype update were the main reasons for identification of these variants in this study.

KW - diagnostic yield

KW - DNAH14

KW - DRG1

KW - ID

KW - LIN7B

KW - RIC3

KW - SYCL2

KW - variant interpretation

KW - whole-exome sequencing

UR - http://www.scopus.com/inward/record.url?scp=85053398231&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053398231&partnerID=8YFLogxK

U2 - 10.1111/cge.13438

DO - 10.1111/cge.13438

M3 - Article

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

ER -