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Key challenges encountered during autonomous WES implementation in Algeria, with contextual evidence and implemented or planned solutions. Challenges operate at two interconnected levels: interpretive (dark grey, relating to population underrepresentation, VUS burden, and consanguinity) and ethical/structural (medium grey, relating to incidental findings, infrastructure, and territorial access). Each challenge is paired with its evidentiary context and the corresponding response developed within this programme. ACMG, American College of Medical Genetics and Genomics; AI, artificial intelligence (here: in-house computational tools for variant prioritisation and interpretation); AMinGen, Application for Medical Inquiry and Nexus in Genornics (national clinical genetics referral platform); AMP, Association for Molecular Pathology; ATM, ataxia telangiectasia mutated gene; CERIST, ResearchCentre for Scientific and Technical Information; DzNA, Database of Algerian variants and allele frequencies; HPO, Human Phenotype Ontology; MH, malignant hyperthermia; ROH, runs of homozygosity; RYRl, ryanodine receptor 1 gene; VUS, variant of uncertain significance; WES, <t>whole-exome</t> sequencing.
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Key challenges encountered during autonomous WES implementation in Algeria, with contextual evidence and implemented or planned solutions. Challenges operate at two interconnected levels: interpretive (dark grey, relating to population underrepresentation, VUS burden, and consanguinity) and ethical/structural (medium grey, relating to incidental findings, infrastructure, and territorial access). Each challenge is paired with its evidentiary context and the corresponding response developed within this programme. ACMG, American College of Medical Genetics and Genomics; AI, artificial intelligence (here: in-house computational tools for variant prioritisation and interpretation); AMinGen, Application for Medical Inquiry and Nexus in Genornics (national clinical genetics referral platform); AMP, Association for Molecular Pathology; ATM, ataxia telangiectasia mutated gene; CERIST, ResearchCentre for Scientific and Technical Information; DzNA, Database of Algerian variants and allele frequencies; HPO, Human Phenotype Ontology; MH, malignant hyperthermia; ROH, runs of homozygosity; RYRl, ryanodine receptor 1 gene; VUS, variant of uncertain significance; WES, <t>whole-exome</t> sequencing.
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Key challenges encountered during autonomous WES implementation in Algeria, with contextual evidence and implemented or planned solutions. Challenges operate at two interconnected levels: interpretive (dark grey, relating to population underrepresentation, VUS burden, and consanguinity) and ethical/structural (medium grey, relating to incidental findings, infrastructure, and territorial access). Each challenge is paired with its evidentiary context and the corresponding response developed within this programme. ACMG, American College of Medical Genetics and Genomics; AI, artificial intelligence (here: in-house computational tools for variant prioritisation and interpretation); AMinGen, Application for Medical Inquiry and Nexus in Genornics (national clinical genetics referral platform); AMP, Association for Molecular Pathology; ATM, ataxia telangiectasia mutated gene; CERIST, ResearchCentre for Scientific and Technical Information; DzNA, Database of Algerian variants and allele frequencies; HPO, Human Phenotype Ontology; MH, malignant hyperthermia; ROH, runs of homozygosity; RYRl, ryanodine receptor 1 gene; VUS, variant of uncertain significance; WES, <t>whole-exome</t> sequencing.
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Key challenges encountered during autonomous WES implementation in Algeria, with contextual evidence and implemented or planned solutions. Challenges operate at two interconnected levels: interpretive (dark grey, relating to population underrepresentation, VUS burden, and consanguinity) and ethical/structural (medium grey, relating to incidental findings, infrastructure, and territorial access). Each challenge is paired with its evidentiary context and the corresponding response developed within this programme. ACMG, American College of Medical Genetics and Genomics; AI, artificial intelligence (here: in-house computational tools for variant prioritisation and interpretation); AMinGen, Application for Medical Inquiry and Nexus in Genornics (national clinical genetics referral platform); AMP, Association for Molecular Pathology; ATM, ataxia telangiectasia mutated gene; CERIST, ResearchCentre for Scientific and Technical Information; DzNA, Database of Algerian variants and allele frequencies; HPO, Human Phenotype Ontology; MH, malignant hyperthermia; ROH, runs of homozygosity; RYRl, ryanodine receptor 1 gene; VUS, variant of uncertain significance; WES, <t>whole-exome</t> sequencing.
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Key challenges encountered during autonomous WES implementation in Algeria, with contextual evidence and implemented or planned solutions. Challenges operate at two interconnected levels: interpretive (dark grey, relating to population underrepresentation, VUS burden, and consanguinity) and ethical/structural (medium grey, relating to incidental findings, infrastructure, and territorial access). Each challenge is paired with its evidentiary context and the corresponding response developed within this programme. ACMG, American College of Medical Genetics and Genomics; AI, artificial intelligence (here: in-house computational tools for variant prioritisation and interpretation); AMinGen, Application for Medical Inquiry and Nexus in Genornics (national clinical genetics referral platform); AMP, Association for Molecular Pathology; ATM, ataxia telangiectasia mutated gene; CERIST, ResearchCentre for Scientific and Technical Information; DzNA, Database of Algerian variants and allele frequencies; HPO, Human Phenotype Ontology; MH, malignant hyperthermia; ROH, runs of homozygosity; RYRl, ryanodine receptor 1 gene; VUS, variant of uncertain significance; WES, <t>whole-exome</t> sequencing.
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Key challenges encountered during autonomous WES implementation in Algeria, with contextual evidence and implemented or planned solutions. Challenges operate at two interconnected levels: interpretive (dark grey, relating to population underrepresentation, VUS burden, and consanguinity) and ethical/structural (medium grey, relating to incidental findings, infrastructure, and territorial access). Each challenge is paired with its evidentiary context and the corresponding response developed within this programme. ACMG, American College of Medical Genetics and Genomics; AI, artificial intelligence (here: in-house computational tools for variant prioritisation and interpretation); AMinGen, Application for Medical Inquiry and Nexus in Genornics (national clinical genetics referral platform); AMP, Association for Molecular Pathology; ATM, ataxia telangiectasia mutated gene; CERIST, ResearchCentre for Scientific and Technical Information; DzNA, Database of Algerian variants and allele frequencies; HPO, Human Phenotype Ontology; MH, malignant hyperthermia; ROH, runs of homozygosity; RYRl, ryanodine receptor 1 gene; VUS, variant of uncertain significance; WES, <t>whole-exome</t> sequencing.
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Key challenges encountered during autonomous WES implementation in Algeria, with contextual evidence and implemented or planned solutions. Challenges operate at two interconnected levels: interpretive (dark grey, relating to population underrepresentation, VUS burden, and consanguinity) and ethical/structural (medium grey, relating to incidental findings, infrastructure, and territorial access). Each challenge is paired with its evidentiary context and the corresponding response developed within this programme. ACMG, American College of Medical Genetics and Genomics; AI, artificial intelligence (here: in-house computational tools for variant prioritisation and interpretation); AMinGen, Application for Medical Inquiry and Nexus in Genornics (national clinical genetics referral platform); AMP, Association for Molecular Pathology; ATM, ataxia telangiectasia mutated gene; CERIST, ResearchCentre for Scientific and Technical Information; DzNA, Database of Algerian variants and allele frequencies; HPO, Human Phenotype Ontology; MH, malignant hyperthermia; ROH, runs of homozygosity; RYRl, ryanodine receptor 1 gene; VUS, variant of uncertain significance; WES, <t>whole-exome</t> sequencing.
Hybrid Capture Probes, supplied by Twist Bioscience, used in various techniques. Bioz Stars score: 86/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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Key challenges encountered during autonomous WES implementation in Algeria, with contextual evidence and implemented or planned solutions. Challenges operate at two interconnected levels: interpretive (dark grey, relating to population underrepresentation, VUS burden, and consanguinity) and ethical/structural (medium grey, relating to incidental findings, infrastructure, and territorial access). Each challenge is paired with its evidentiary context and the corresponding response developed within this programme. ACMG, American College of Medical Genetics and Genomics; AI, artificial intelligence (here: in-house computational tools for variant prioritisation and interpretation); AMinGen, Application for Medical Inquiry and Nexus in Genornics (national clinical genetics referral platform); AMP, Association for Molecular Pathology; ATM, ataxia telangiectasia mutated gene; CERIST, ResearchCentre for Scientific and Technical Information; DzNA, Database of Algerian variants and allele frequencies; HPO, Human Phenotype Ontology; MH, malignant hyperthermia; ROH, runs of homozygosity; RYRl, ryanodine receptor 1 gene; VUS, variant of uncertain significance; WES, whole-exome sequencing.

Journal: medRxiv

Article Title: Challenges and perspectives in implementing whole-exome sequencing in Algeria: lessons from a fully autonomous in-country cohort

doi: 10.64898/2026.03.23.26348909

Figure Lengend Snippet: Key challenges encountered during autonomous WES implementation in Algeria, with contextual evidence and implemented or planned solutions. Challenges operate at two interconnected levels: interpretive (dark grey, relating to population underrepresentation, VUS burden, and consanguinity) and ethical/structural (medium grey, relating to incidental findings, infrastructure, and territorial access). Each challenge is paired with its evidentiary context and the corresponding response developed within this programme. ACMG, American College of Medical Genetics and Genomics; AI, artificial intelligence (here: in-house computational tools for variant prioritisation and interpretation); AMinGen, Application for Medical Inquiry and Nexus in Genornics (national clinical genetics referral platform); AMP, Association for Molecular Pathology; ATM, ataxia telangiectasia mutated gene; CERIST, ResearchCentre for Scientific and Technical Information; DzNA, Database of Algerian variants and allele frequencies; HPO, Human Phenotype Ontology; MH, malignant hyperthermia; ROH, runs of homozygosity; RYRl, ryanodine receptor 1 gene; VUS, variant of uncertain significance; WES, whole-exome sequencing.

Article Snippet: Exome enrichment targeting all coding exons and flanking canonical splice junctions within approximately ±50 bp was performed using the MGIEasy Exome Capture V5 probe set (MGI Tech).

Techniques: Variant Assay, Sequencing