// Evidence Grader
Claim grades, A through F
Every major genomics claim in this course gets a transparent grade — from clinically established interventions to outright misleading marketing. Use this dashboard to audit what's settled, what's preliminary, and what's hype.
A
Clinically established
B
Supported, context-specific
C
Promising, preliminary
D
Plausible, unproven
E
Popular, weak support
F
Misleading or false
Filtered:
B
Whole-exome sequencing has higher diagnostic yield than gene panels for most rare-disease workups
True for broad/atypical phenotypes; panels still preferred for well-defined disease with clear-cut gene lists.
Module 02 · Reading the Genome: Platforms & Modalities →B
CYP2D6 genotype-guided dosing improves outcomes for SSRIs
Improves tolerability and time-to-remission in some RCTs (GUIDED, IMPACT); effect modest and population-dependent.
Module 04 · Pharmacogenomics in Practice →B
Tumor mutational burden (TMB) predicts checkpoint-inhibitor response across all solid tumors
Validated in NSCLC, melanoma, MSI-H/dMMR; pan-tumor cutoffs (≥10 mut/Mb) are imperfect.
Module 05 · Cancer Genomics: Germline, Somatic, and Liquid →B
PRS adds incremental discrimination on top of pooled cohort equations / QRISK3
Modest C-statistic gain (~0.01–0.02) but meaningful net reclassification at intermediate-risk thresholds.
Module 06 · Polygenic Risk & Early Warning →B
PRS-guided breast-cancer screening start age improves cancer detection
BCSC + PRS modeling; pilot programs (CanRisk, MyPeBS) ongoing.
Module 06 · Polygenic Risk & Early Warning →B
Partial reprogramming (cyclic OSK) can reverse epigenetic age in human cells
Sarkar 2020, Lu 2020, Browder 2022 — strong cell/mouse evidence; no published human in-vivo trials yet.
Module 07 · The Epigenome and Methylation Clocks →B
2-year caloric restriction (~12% deficit) slows pace-of-aging biomarkers
CALERIE secondary analysis (Waziry 2023); modest effect, primary endpoints were metabolic.
Module 08 · Lifestyle Inputs to the Epigenome →B
Base editing achieves clinically meaningful PCSK9 lowering after a single in-vivo LNP infusion
VERVE-101 readout interrupted by a transient ALT signal; VERVE-102 with revised LNP underway.
Module 09 · CRISPR Therapeutics: From Casgevy to In Vivo →B
Personalized neoantigen mRNA vaccines reduce melanoma recurrence post-resection
KEYNOTE-942 phase 2 (mRNA-4157 + pembrolizumab) HR ~0.56; phase 3 ongoing.
Module 10 · Beyond CRISPR: ASO, siRNA, mRNA, AAV, and Cell Therapy →B
PARP-inhibitor exposure increases AML/MDS risk in patients with pre-existing CHIP
Suggested by ovarian-cancer pharmacovigilance + mechanistic rationale; absolute risk increase modest.
Module 11 · Clonal Hematopoiesis & Aging Genomes →B
ACMG-recommended opportunistic secondary-finding return improves outcomes for some carriers
Plausible mechanism, supported by single-gene case series; controlled outcome data limited.
Module 12 · Ethics, Equity, and the Germline Question →