Source 1primary paper2026MED
Toolkit/SyMetrics
SyMetrics
Taxonomy: Technique Branch / Method. Workflows sit above the mechanism and technique branches rather than replacing them.
Summary
we developed SyMetrics, a framework that integrates predictors of splicing, RNA stability, evolutionary conservation, codon usage, synonymous variation effects, sequence properties, and allele frequency
Usefulness & Problems
No literature-backed usefulness or problem-fit explainer has been materialized for this record yet.
Published Workflows
Objective: Develop and validate an integrated machine-learning framework for evaluating the pathogenicity of synonymous variants in the human genome.
Why it works: The workflow combines multiple mechanistically relevant predictor classes and then validates predictions using functional assays, existing mutagenesis screens, and clinical cohort interpretation.
splicing effectsRNA stability effectsevolutionary conservationcodon usage effectssynonymous variation effectsfeature integrationmachine learningfunctional assay validationuse of large-scale mutagenesis screensclinical cohort interpretation
Taxonomy & Function
Primary hierarchy
Technique Branch
Method: A concrete computational method used to design, rank, or analyze an engineered system.
Mechanisms
comparative scoring using splicing, rna stability, conservation, codon-usage, sequence-property, and allele-frequency featuresmachine-learning integration of heterogeneous variant-effect predictorsTarget processes
No target processes tagged yet.
Validation
Cell-freeBacteriaMammalianMouseHumanTherapeuticIndep. Replication
Supporting Sources
Ranked Claims
In a clinical cohort, SyMetrics identified 15 predicted deleterious synonymous variants in genes linked to patient phenotypes, of which 9 were classified as likely pathogenic or pathogenic and 6 as variants of uncertain significance.
classified as likely pathogenic or pathogenic 9classified as VUS 6predicted deleterious sSNVs identified in clinical cohort 15
For three variants of uncertain significance, segregation data supported suspected inheritance patterns including de novo and X-linked inheritance.
VUS with supportive segregation data 3
Synonymous variants absent from population databases have higher estimated deleteriousness than common synonymous variants, with an odds ratio of 3.87.
odds ratio for deleteriousness 3.87P value 0.05
Approximately 1.98 ± 0.17% of synonymous variants absent from population databases are estimated to be damaging, corresponding to roughly 900,000 variants.
estimated damaging fraction among sSNVs absent from population databases 1.98 %estimated damaging sSNV count roughly 900000estimate uncertainty 0.17 %
SyMetrics achieved 97% accuracy and ROC-AUC 0.89 for distinguishing deleterious from benign synonymous variants and outperformed individual predictors.
accuracy 97 %ROC-AUC 0.89
Approval Evidence
1 source5 linked approval claimsfirst-pass slug symetrics
we developed SyMetrics, a framework that integrates predictors of splicing, RNA stability, evolutionary conservation, codon usage, synonymous variation effects, sequence properties, and allele frequency
Source:
clinical applicationsupports
In a clinical cohort, SyMetrics identified 15 predicted deleterious synonymous variants in genes linked to patient phenotypes, of which 9 were classified as likely pathogenic or pathogenic and 6 as variants of uncertain significance.
Source:
clinical follow upsupports
For three variants of uncertain significance, segregation data supported suspected inheritance patterns including de novo and X-linked inheritance.
Source:
comparative risksupports
Synonymous variants absent from population databases have higher estimated deleteriousness than common synonymous variants, with an odds ratio of 3.87.
Source:
genome wide estimatesupports
Approximately 1.98 ± 0.17% of synonymous variants absent from population databases are estimated to be damaging, corresponding to roughly 900,000 variants.
Source:
tool performancesupports
SyMetrics achieved 97% accuracy and ROC-AUC 0.89 for distinguishing deleterious from benign synonymous variants and outperformed individual predictors.
Source:
Comparisons
No literature-backed comparison notes have been materialized for this record yet.
Ranked Citations
- 1.