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Atlas — per-cohort ThermoCas9 target shortlists

Per-cohort top-100 candidate PAM sites for ThermoCas9 across four public methylation cohorts, scored under the compositional skeleton p_targ × (gap factor) × p_trust. Headline figure visualizes per-positive whole-genome rank percentiles — including an honest disclosure of the GSE69914 ESR1 reversal under V2.5-sigmoid that the methods paper documents in §6.1.

Source paper: paper-5-10j Atlas tag: memo-2026-04-22-bw Cohorts: 4 (n_pos = 3 Roth Fig. 5d targets) Status: Hypothesis generation only
Scope
Every row on this page is a candidate, not a target. The scoring framework is open educational research. It has been benchmarked retrospectively against four public methylation cohorts, but it has not been validated prospectively against any wet-lab editing readout. Do not select a row from any of the top-100 tables for therapeutic application without running the full freeze-and-validate pipeline described in the external-validation instruction.

Headline figure — per-positive whole-genome rank percentiles

Per-positive whole-genome rank percentiles for the three Roth Fig. 5d positives across four cohort paths, comparing V2.5-diff (open circles) and V2.5-sigmoid (filled circles).
Figure 4. For each of the three Roth Fig. 5d positives (ESR1, EGFLAM, GATA3), the dot-plot shows the rank percentile of that positive's PAM site within the cohort's whole-genome candidate universe (HM450 ≈ 19.8 M loci; EPIC v2 ≈ 35.4 M). Filled circles are V2.5-sigmoid; open circles are V2.5-diff; the line connects the two so the rank-lift direction is immediately visible. Underlying data: per_positive_wg_percentile.json · SVG.

What to read off the plot.

Per-cohort top-100 explorer

Pick a cohort, filter by gene symbol or PAM family. Rows highlighted in the accent color overlap a Roth Fig. 5d positive at the wide (±500 bp) tier. The full per-row schema (30+ columns including RepeatMasker overlap and CGI distance) lives in the per-cohort TSV linked below; this table shows the slim-schema columns that fit on a screen.

Loading atlas data…

Summary by cohort

GSE322563 HM450
Source: Roth MCF-7 / MCF-10A Path: HM450-intersect n_t / n_n: 2 / 2
GSE322563 native EPIC v2
Source: Roth MCF-7 / MCF-10A Path: Native EPIC v2 n_t / n_n: 2 / 2
GSE77348
Source: δ-development cohort Path: HM450 n_t / n_n: 3 / 3
GSE69914 tissue
Source: Primary tumor + healthy donor Path: HM450 n_t / n_n: 305 / 50

How rows on this page map to rows in the paper

What is not in this atlas (intentionally)

Cite or reproduce