Analytical validation of GenoPharm a clinical genotyping open array panel of 46 pharmacogenes inclusive of variants unique to people of African ancestry

Kanji, Comfort Ropafadzo; Mbavha, Bianza Tinotenda; Masimirembwa, Collen; Thelingwani, Roslyn Stella

doi:10.1371/journal.pone.0292131

Cited by 4 publications

(2 citation statements)

References 34 publications

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“…The data presented here further support previous efforts calling for prioritization within disease areas and/or drug-gene pairs or drug classes within Southern Africa [43][44][45]. With the clinical genotyping of South African and Zimbabwean cohorts using a 46 gene panel revealing that 100% of participants harboured at least one actionable PGx variant, with a median distribution of four actionable variants [46], foregoing implementation has serious consequences for patients in sub-Saharan Africa. While concerns have been raised regarding the magnitude of ADR reduction reported in the PREPARE study, along with the limitations of focusing on only ADRs as an outcome in pharmacogenetic testing [47,48], it has also been argued that the reported effect size remains plausible due the limited scope and scale of the study.…”

Section: Discussionsupporting

confidence: 80%

The Case for Pre-Emptive Pharmacogenetic Screening in South Africa

Hurrell,

Naidoo,

Masimirembwa

et al. 2024

JPM

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Lack of equitable representation of global genetic diversity has hampered the implementation of genomic medicine in under-represented populations, including those on the African continent. Data from the multi-national Pre-emptive Pharmacogenomic Testing for Preventing Adverse Drug Reactions (PREPARE) study suggest that genotype guidance for prescriptions reduced the incidence of clinically relevant adverse drug reactions (ADRs) by 30%. In this study, hospital dispensary trends from a tertiary South African (SA) hospital (Steve Biko Academic Hospital; SBAH) were compared with the drugs monitored in the PREPARE study. Dispensary data on 29 drugs from the PREPARE study accounted for ~10% of total prescriptions and ~9% of the total expenditure at SBAH. VigiLyze data from the South African Health Products Regulatory Authority were interrogated for local ADRs related to these drugs; 27 were listed as being suspected, concomitant, or interacting in ADR reports. Furthermore, a comparison of pharmacogene allele frequencies between African and European populations was used to frame the potential impact of pre-emptive pharmacogenetic screening in SA. Enumerating the benefit of pre-emptive pharmacogenetic screening in SA will only be possible once we initiate its full application. However, regional genomic diversity, disease burden, and first-line treatment options could be harnessed to target stratified PGx today.

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Section: Discussionsupporting

confidence: 80%

The Case for Pre-Emptive Pharmacogenetic Screening in South Africa

Hurrell,

Naidoo,

Masimirembwa

et al. 2024

JPM

Self Cite

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“…Overall, our workflow was demonstrated to exhibit both accuracy and precision. When compared to other array-based PGx assays, our test exhibited performance levels closely aligned with the reported literature standards for accuracy (ranging from 93% to 100%) and precision (ranging from 97% to 100%) ( Hartshorne et al, 2013 ; Martins et al, 2013 ; Borobia et al, 2018 ; Collins et al, 2019 ; Tang et al, 2021 ; Kanji et al, 2023 ).…”

Section: Discussionsupporting

confidence: 80%

Development and validation of a pharmacogenomics reporting workflow based on the illumina global screening array chip

Gan,

Hajis,

Yumna

et al. 2024

Front. Pharmacol.

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Background: Microarrays are a well-established and widely adopted technology capable of interrogating hundreds of thousands of loci across the human genome. Combined with imputation to cover common variants not included in the chip design, they offer a cost-effective solution for large-scale genetic studies. Beyond research applications, this technology can be applied for testing pharmacogenomics, nutrigenetics, and complex disease risk prediction. However, establishing clinical reporting workflows requires a thorough evaluation of the assay’s performance, which is achieved through validation studies. In this study, we performed pre-clinical validation of a genetic testing workflow based on the Illumina Global Screening Array for 25 pharmacogenomic-related genes.Methods: To evaluate the accuracy of our workflow, we conducted multiple pre-clinical validation studies. Here, we present the results of accuracy and precision assessments, involving a total of 73 cell lines. These assessments encompass reference materials from the Genome-In-A-Bottle (GIAB), the Genetic Testing Reference Material Coordination Program (GeT-RM) projects, as well as additional samples from the 1000 Genomes project (1KGP). We conducted an accuracy assessment of genotype calls for target loci in each indication against established truth sets.Results: In our per-sample analysis, we observed a mean analytical sensitivity of 99.39% and specificity 99.98%. We further assessed the accuracy of star-allele calls by relying on established diplotypes in the GeT-RM catalogue or calls made based on 1KGP genotyping. On average, we detected a diplotype concordance rate of 96.47% across 14 pharmacogenomic-related genes with star allele-calls. Lastly, we evaluated the reproducibility of our findings across replicates and observed 99.48% diplotype and 100% phenotype inter-run concordance.Conclusion: Our comprehensive validation study demonstrates the robustness and reliability of the developed workflow, supporting its readiness for further development for applied testing.

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Development and validation of a pharmacogenomics reporting workflow based on the Illumina Global Screening Array chip

Gan,

Hajis,

Yumna

et al. 2023

Preprint

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BackgroundMicroarrays are a well-established and widely adopted technology capable of interrogating hundreds of thousands of loci across the human genome. Combined with imputation to cover common variants not included in the chip design, they offer a cost-effective solution for large-scale genetic studies. Beyond research applications, this technology can be applied for testing pharmacogenomics, nutrigenetics, and complex disease risk prediction.However, establishing clinical reporting workflows requires a thorough evaluation of the assay’s performance, which is achieved through validation studies. In this study, we performed pre-clinical validation of a genetic testing workflow based on the Illumina Global Screening Array for 25 pharmacogenomic-related genes.MethodsTo evaluate the accuracy of our workflow, we conducted multiple pre-clinical validation studies. Here, we present the results of accuracy and precision assessments, involving a total of 73 cell lines. These assessments encompass reference materials from the Genome-In-A-Bottle (GIAB), the Genetic Testing Reference Material Coordination Program (GeT-RM) projects, as well as additional samples from the 1000 Genomes project (1KGP). We conducted an accuracy assessment of genotype calls for target loci in each indication against established truth sets.ResultsIn our per-sample analysis, we observed a mean analytical sensitivity of 99.39% and specificity 99.98%. We further assessed the accuracy of star-allele calls by relying on established diplotypes in the GeT-RM catalogue or calls made based on 1KGP genotyping. On average, we detected a diplotype concordance rate of 96.47% across 14 pharmacogenomic-related genes with star allele-calls. Lastly, we evaluated the reproducibility of our findings across replicates and observed 99.48% diplotype and 100 % phenotype inter-run concordance.ConclusionOur comprehensive validation study demonstrates the robustness and reliability of the developed workflow, supporting its readiness for further development for applied testing.

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Analytical validation of GenoPharm a clinical genotyping open array panel of 46 pharmacogenes inclusive of variants unique to people of African ancestry

Cited by 4 publications

References 34 publications

The Case for Pre-Emptive Pharmacogenetic Screening in South Africa

The Case for Pre-Emptive Pharmacogenetic Screening in South Africa

Development and validation of a pharmacogenomics reporting workflow based on the illumina global screening array chip

Development and validation of a pharmacogenomics reporting workflow based on the Illumina Global Screening Array chip

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