bioinformatics pipeline for rare genetic diseases in South African patients

Abstract

The research fields of bioinformatics and computational biology are growing rapidly in South Africa. Bioinformatics pipelines play an integral part in handling sequencing data, which are used to investigate the aetiology of common and rare diseases. Bioinformatics platforms for common disease aetiology are well supported and continuously being developed in South Africa. However, the same is not the case for rare diseases aetiology research. Investigations into the latter rely on international cloud-based tools for data analyses and ultimately confirmation of a genetic disease. However, these tools are not necessarily optimised for ethnically diverse population groups. We present an in-house developed bioinformatics pipeline to enable researchers to annotate and filter variants in either exome or amplicon next-generation sequencing data. This pipeline was developed using next-generation sequencing data of a predominantly African cohort of patients diagnosed with rare disease. Significance: We demonstrate the feasibility of in-country development of ethnicity-sensitive, automated bioinformatics pipelines using free software in a South African context. We provide a roadmap for development of similarly ethnicity-sensitive bioinformatics pipelines.

Characterization of Genetic Variants in the SLC5A5 Gene and Associations With Breast Milk Iodine Concentration in Lactating Women of African Descent: The NUPED Study

“…The sequence files were aligned against Genome Reference Consortium Human Build 37 (hg19), followed by coverage analysis and variant calling using the coverage analysis and variantCaller plugins from the Torrent Suite, respectively. Secondary data analyses of the variant caller files were annotated, filtered and mined following an in-house pipeline (15).…”

Current Status of Next-Generation Sequencing Approaches for Candidate Gene Discovery in Familial Parkinson´s Disease

“…Another initiative is the H3Africa Consortium which aims to develop a pan-African bioinformatics network (H3ABionet) and infrastructure to enhance African genomics research on the continent ( Mulder et al, 2017 ). Additionally, South African researchers have developed a secondary data analysis pipeline to overcome the lack of African allele frequency data in population databases ( Schoonen et al, 2019 ). Their software incorporates Ensembls Variant Effect Predictor ( https://www.ensembl.org/info/docs/tools/vep ) to annotate variants and GEnome MINIng (GEMINI v0.20) ( https://gemini.readthedocs.io/ ) to effectively filter variants according to African allele frequencies, resulting in higher quality output ( Schoonen et al, 2019 ).…”

“…Additionally, South African researchers have developed a secondary data analysis pipeline to overcome the lack of African allele frequency data in population databases ( Schoonen et al, 2019 ). Their software incorporates Ensembls Variant Effect Predictor ( https://www.ensembl.org/info/docs/tools/vep ) to annotate variants and GEnome MINIng (GEMINI v0.20) ( https://gemini.readthedocs.io/ ) to effectively filter variants according to African allele frequencies, resulting in higher quality output ( Schoonen et al, 2019 ). Furthermore, international efforts in PD are underway to bring underrepresented populations to the fore, through standardized NGS data storage and analysis, as seen with the Global Parkinson’s Genetics Program ( Global Parkinson’s Genetics Program., 2021 ) that aims to sequence and analyze PD-affected, at-risk and control individuals from diverse populations to bridge the gap in the ‘missing heritability’ witnessed in PD.…”