Bioinformatics & AI

Week of 15 September 2026

11 articles

Geno'X Veille — genox-veille.fr

Key takeaways this week

►Serum proteomics — 13 confirmed diagnoses among 424 patients still negative after genome sequencing.
►Tumor mutational signatures — an explicit likelihood ratio reclassifies 38 of 45 MMR variants of uncertain significance.
►Long-read genome — 4.7% incremental diagnostic yield in cases already negative on short-read sequencing.
►GPN-Star — a phylogeny-aware language model reaching state-of-the-art prioritization of pathogenic coding and non-coding variants.
►SPLENDID — polygenic prediction without ancestry labels, validated in All of Us and UK Biobank.

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Variant interpretation

Bayesian Integration of Tumor Mutational Signatures and Somatic Features Refines Pathogenicity Assessment of Germline Mismatch Repair Variants.

Lynch syndrome — germline variant classification

Variant interpretationPathogenicity predictionClinical pipeline

Hum Mutat 2026· SepRead

Variant interpretation

Proteomics identify disease-associated variants in patients with rare diseases undiagnosed after genome sequencing.

Rare disease undiagnosed after genome sequencing

Variant interpretationClinical pipeline

Sci Transl Med 2026· SepRead

Pathogenicity prediction

Predicting genome-wide functional constraints with GPN-Star.

Variant interpretation — genome-wide prediction

Pathogenicity predictionNew toolPathogenicity prediction

Nature 2026· SepRead

Polygenic risk score

SPLENDID incorporates continuous genetic ancestry in biobank-scale data to improve polygenic risk prediction across diverse populations.

Polygenic risk prediction across diverse populations

Polygenic risk scoreNew toolBenchmark

Nat Methods 2026· SepRead

Yield of Long-Read Genome Sequencing for Rare Disease Diagnosis in Short-Read Genome Negative Cases

Mendelian conditions — long-read genome diagnosis

Long-readLong-read sequencingClinical pipeline

medRxiv 2026· SepRead

Variant interpretation

Empirically calibrated allele frequency thresholds for ACMG BA1, BS1 and PM2 evidence criteria

Variant classification — ACMG allele frequency criteria

Variant interpretationPathogenicity predictionClinical pipeline

medRxiv 2026· SepRead

Language model / AI

Genomic language model for predicting enhancers and their allele-specific activity in the human genome.

Enhancer annotation and non-coding variants

Language model / AINew toolLLM applied

Bioinformatics 2026· SepRead

Structural variants

COSIGT: population-scalable genotyping of complex loci from low-coverage sequencing data using pangenome graphs.

Complex locus genotyping

Structural variantsNew toolBenchmark

Genome Biol 2026· SepRead

Pathogenicity prediction

CanVar-UK: A collaborative platform for germline interpretation in cancer susceptibility genes.

Hereditary cancer predisposition — variant interpretation

Pathogenicity predictionNew toolClinical pipeline

Am J Hum Genet 2026· SepRead

Clinical pipeline

TargetQC: A targeted quality control framework for clinical genomic testing.

Quality control of clinical sequencing

Clinical pipelineNew toolBenchmark

iScience 2026· AugRead

Structural variants

Optical genome mapping improves structural variant detection and characterization in syndromic and neurogenetic disorders.

Neurogenetic and syndromic disorders — structural variants

Structural variantsClinical pipeline

Hum Genet 2026· SepRead

References and sources

Variant interpretation — genome-wide prediction. Nature 2026. PMID 42717086. Score 8/10. https://pubmed.ncbi.nlm.nih.gov/42717086/
Rare disease undiagnosed after genome sequencing. Sci Transl Med 2026. PMID 42715344. Score 9/10. https://pubmed.ncbi.nlm.nih.gov/42715344/
Lynch syndrome — germline variant classification. Hum Mutat 2026. PMID 42719515. Score 10/10. https://pubmed.ncbi.nlm.nih.gov/42719515/
Mendelian conditions — long-read genome diagnosis. medRxiv 2026. doi:10.64898/2026.09.09.26362331. Score 7/10. https://www.medrxiv.org/content/10.64898/2026.09.09.26362331v1
Polygenic risk prediction across diverse populations. Nat Methods 2026. PMID 42736360. Score 8/10. https://pubmed.ncbi.nlm.nih.gov/42736360/
Enhancer annotation and non-coding variants. Bioinformatics 2026. PMID 42723633. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42723633/
Complex locus genotyping. Genome Biol 2026. PMID 42711702. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42711702/
Variant classification — ACMG allele frequency criteria. medRxiv 2026. doi:10.64898/2026.09.07.26362456. Score 7/10. https://www.medrxiv.org/content/10.64898/2026.09.07.26362456v1
Quality control of clinical sequencing. iScience 2026. PMID 42729446. Score 5/10. https://pubmed.ncbi.nlm.nih.gov/42729446/
Hereditary cancer predisposition — variant interpretation. Am J Hum Genet 2026. PMID 42727578. Score 6/10. https://pubmed.ncbi.nlm.nih.gov/42727578/
Neurogenetic and syndromic disorders — structural variants. Hum Genet 2026. PMID 42720813. Score 5/10. https://pubmed.ncbi.nlm.nih.gov/42720813/

8 September 2026