ArticleScientific reports2019
New insights into the pathogenicity of non-synonymous variants through multi-level analysis.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04033965 (Tumor Mutational Patterns and Infiltrating Lymphocyte Density in Young and Old Patients With Breast Cancer), which is not on this map. Cited by 43 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Tumor Mutational Patterns and Infiltrating Lymphocyte Density in Young and Old Patients With Breast Cancer
Who cites it
43 citing papers in PubMed.
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- Computational analysis of MYC gene variants: structural and functional impact of non-synonymous SNPs.Journal of applied genetics · 2026Article
- PRP: pathogenic risk prediction for rare nonsynonymous single nucleotide variants.Human genetics · 2025Article
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- Identification of novel RIPK4 variants in a Chinese patient with Arthrogryposis Multiplex Congenita (AMC).Italian journal of pediatrics · 2025Article
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- Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C).The Journal of experimental medicine · 2024Article
- AI-derived comparative assessment of the performance of pathogenicity prediction tools on missense variants of breast cancer genes.Human genomics · 2024Article
- Variant Effect Prediction in the Age of Machine Learning.Cold Spring Harbor perspectives in biology · 2024Review
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- Identification of a Novel Deletion Variant (c.2999_3005delTGTGTGT/p.Asn1000SerfsTer4) in NPHP4 Associated With Nephronophthisis-4.Journal of clinical laboratory analysis · 2024Article
- Rare GPR37L1 Variants Reveal Potential Association between GPR37L1 and Disorders of Anxiety and Migraine.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Prioritizing genomic variants through neuro-symbolic, knowledge-enhanced learning.Bioinformatics (Oxford, England) · 2024Article
- DrivR-Base: a feature extraction toolkit for variant effect prediction model construction.Bioinformatics (Oxford, England) · 2024Article
- MLe-KCNQ2: An Artificial Intelligence Model for the Prognosis of MissenseInternational journal of molecular sciences · 2024Article
- Plasminogen missense variants and their involvement in cardiovascular and inflammatory disease.Frontiers in cardiovascular medicine · 2024Review
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2 authors.
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Abstract
Precise classification of non-synonymous single nucleotide variants (SNVs) is a fundamental goal of clinical genetics. Next-generation sequencing technology is effective for establishing the basis of genetic diseases. However, identification of variants that are causal for genetic diseases remains a challenge. We analyzed human non-synonymous SNVs from a multilevel perspective to characterize pathogenicity. We showed that computational tools, though each having its own strength and weakness, tend to be overly dependent on the degree of conservation. For the mutations at non-degenerate sites, the amino acid sites of pathogenic substitutions show a distinct distribution in the classes of protein domains compared with the sites of benign substitutions. Overlooked disease susceptibility of genes explains in part the failures of computational tools. The more pathogenic sites observed, the more likely the gene is expressed in a high abundance or in a high tissue-specific manner, and have a high node degree of protein-protein interaction. The destroyed functions due to some false-negative mutations may arise because of a reprieve from the epigenetic repressed state which shouldn't happen in multiple biological conditions, instead of the defective protein. Our work adds more to our knowledge of non-synonymous SNVs' pathogenicity, thus will benefit the field of clinical genetics.
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