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"The beauty of a living thing is not the atoms that go into it, but the way those atoms are put together."
- Carl Sagan
Quick Analysis Plan
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Goal
Build an analysis + visualization workflow that takes RAD51 foci induction data and produces Type-I vs Type-II comparisons (and optionally kinetics) after DNA damageβgrounded in how RAD51 foci quantify HR activation across perturbations.
Uses the common experimental logic: RAD51 foci quantification as an HR-associated marker after DNA damage, and how perturbations (e.g., RAD51 mutants, RAD51 regulators) shift foci/foci-positive fraction and repair phenotypes.
Long Analysis Plan
RAD51 foci induction: Type I vs Type II after DNA damage
Scientific output: (1) robust data schema, (2) normalization choices, (3) statistical tests, (4) Plotly figures (induction, kinetics, and Type-I/Type-II composition).
1) What βType I vs Type IIβ should mean (you must define it)
βType I/Type IIβ is not a universal RAD51-foci standard in the provided sources, so you should operationalize it from your microscopy features (examples: size, intensity, counts per nucleus, colocalization with Ξ³H2AX, or appearance pattern over time).
A key skepticism point: RAD51 βfociβ can reflect different molecular assemblies/contexts; foci quantification is informative but can be correlative without orthogonal HR/resection/restart readouts.
Minimum feature set for type-calling
Per nucleus: total RAD51 foci count, fraction RAD51+ nuclei, per-foci intensity/area (distributions).
Per foci: area (pxΒ²), integrated intensity, maximum intensity, circularity/texture.
RAD51 foci quantification is widely used; e.g., studies report changes in RAD51 foci per cell or the percentage of RAD51-positive cells after X-ray or replication stress.
3) Normalization & summary metrics (define before statistics)
Induction: compare each condition vs its matched control (same cell line/genotype/batch):
Foci-positive fraction: p = (# RAD51+ nuclei) / (total nuclei)
Mean foci per nucleus (or per RAD51+ nucleus) depending on your biological question
Type composition (crucial for your Type I/II question):
Type I fraction among all RAD51 foci: f_I = N_I / (N_I + N_II)
Type-specific per-cell burden: N_I per nucleus and N_II per nucleus
Kinetics: plot timepoint-resolved induction curves; avoid mixing timepoints in a single bar figure.
Counterpoint: if Type I/II are derived from intensity/size thresholds, batch effects can dominate; therefore you should include batch as a blocking variable or standardize thresholds using negative/vehicle controls within each batch.
4) Statistics (skeptical, assumption-aware)
Use a model that respects per-cell counts (binomial for RAD51+ fraction; negative binomial / zero-inflated if you have many zero nuclei for foci counts). Keep replicates independent.
RAD51+ fraction (Type-agnostic): hierarchical binomial with replicate as random effect.
Per-cell foci: negative binomial GLM (or median comparisons if distributions are highly non-normal).
Type composition per cell: model N_I and N_II jointly (multinomial/Dirichlet-multinomial) or treat foci-level as objects with clustered errors.
Multiple testing: control FDR across timepoints/conditions.
5) Plotly figures (grounded in provided numeric examples)
Below, I include only figures I can populate from the provided research excerpts. If your own dataset contains Type I/Type II labels, you will extend these plots using your raw data.
This is an example visualization using the provided numeric excerpt for RAD51 foci-positive fractions under CPT sensitivity experiments in Swsap1-/- vs WT.
The provided excerpt shows that RAD51-II3A can preserve RAD51 foci yet fails to robustly restore HR reporter activity, motivating why Type I/II foci should be interpreted together with HR function readouts.
Type I/II composition is computed from your microscopy segmentation outputs (N_I and N_II). The underlying interpretive cautionβthat foci alone may not fully predict HR functionβis supported by RAD51-II3A vs WT HR reporter differences.
6) Optional: incorporate DDR/repair pathway context (how to enrich interpretation)
If your Type I/II definitions include overlap with Ξ³H2AX, you can interpret RAD51 dynamics in the broader DSB repair context. For example, perturbing HR/NHEJ regulators can shift RAD51 recruitment patterns and foci intensities.
Ingest your nucleus/foci tables (CSV/Parquet) into a single tidy format.
Compute per-nucleus metrics: rad51_positive, total foci, intensity summaries.
Type-calling: assign foci_type (I/II) from your feature thresholds (or clustering trained on controls).
Aggregate per condition/timepoint/replicate:
Fraction positive p
Mean foci per nucleus
Type I/II counts and fractions
Plot with Plotly:
Bar/point plots: induced p vs control
Stacked composition: f_I vs timepoint
Violin/ECDF: foci intensity/area distributions by type
Stats: run replicate-aware tests; export effect sizes + CIs.
Report a reproducible βfoci-type definitionβ section (thresholds, quality control plots, batch corrections).
Next step (optional)
If you upload your raw per-nucleus and per-foci data (or screenshots + exported segmentation measurements), BGPT can compute Type I/II induction curves and generate publication-ready Plotly panels.
Compute per-condition RAD51+ fraction, total foci per nucleus, and Type I/II composition from your nucleus/foci tables; then generate induction and kinetics Plotly panels and replicate-aware effect-size statistics.
Get emailed when your analysis is done!
We'll email you the results when your analysis is finished.
Hypothesis Graveyard
If Type I/II are only intensity-threshold artifacts of imaging exposure, then changing exposure/threshold will swap Type labels without changing HR functionβmaking Type composition non-biological; this is rejected by requiring threshold-stable classification across batches.
If Type I/II differ only in foci size but not in overlap with functional readouts (HR reporter, restart assays), then the Type classifier is not mechanistically informative and should be replaced by a simpler metric (total RAD51+ fraction or mean per cell).