Traceable Claims in Genomics

 Quick Analysis Plan Copied

 Long Analysis Plan

Evidence-anchored genetics analysis plan

Stage 1 — Data ingestion & QC. Standardize FASTQ/BAM/VCF inputs with nf-core pipelines; validate pedigree structures and phenotype harmonization before any association testing. Family-based designs (e.g., transmission/disequilibrium testing) remain robust to population stratification, as used in the Finnish celiac study of 100 families with seven microsatellite markers CD28/CTLA4 celiac linkage study.

Stage 2 — Variant discovery & association. Joint-call variants (GATK), QC on depth/HWE, then GWAS or TDT. For expression-layer questions, integrate Ribo-seq/RNA-seq visualization to detect novel ORFs and translational regulation, e.g., via the ggRibo R package validated on human and Arabidopsis datasets ggRibo Ribo-seq visualization tool.

Stage 3 — Regulatory & epigenetic interpretation. Annotate variants against transposable-element regulatory landscapes, since TEs contribute regulatory sequences and chromatin effects that shape gene expression and disease risk TE gene regulation review. Where phenotype data are longitudinal and clonal (genotype-controlled), quantify non-genetic inheritance via mixed-effects repeatability models — the Amazon molly study found maternal feeding predicted ~32.9% of offspring activity variance (p=0.001) across 34 mothers and 232 offspring Clonal fish non-genetic inheritance study.

Stage 4 — Reporting. Report effect sizes, confidence intervals, and preregistered falsification criteria; flag known limitations: small family cohorts (n=100), population restriction (Finnish; UK Biobank white participants aged 40–69, n=288,031 for gene×environment CAD work UK Biobank genetic susceptibility CAD study), and over-expression artifacts in model organisms (53.8% of OsSET1-transgenic Arabidopsis showed abnormal shoots — an over-expression, not loss-of-function, result OsSET1 rice SET-domain gene study).

Key unknowns: causal variant at 2q33 unresolved by microsatellite-level linkage; mechanisms of maternal-state transmission (epigenetic marks inferred, not demonstrated); generalizability across ancestries and to natural environments untested.