OMICSCHAT

Purpose

Your genome has 3 billion base pairs. Your variant report has 47 findings. You need someone who can tell you which ones matter.

OMICSCHAT is genomic intelligence for precision medicine — the governed companion that classifies variants per ACMG/AMP, maps pharmacogenomic interactions, interprets gene expression panels, and matches you to precision medicine trials. You ask it whether your BRCA2 variant is pathogenic or a VUS, whether your DPYD genotype means you need a dose reduction on 5-FU, or which trials are recruiting for your EGFR exon 19 deletion — and it gives you a tiered, sourced answer from ClinVar, PharmGKB, and ClinicalTrials.gov.

Think a molecular tumor board, but accessible — every variant classified, every finding evidence-tiered, every protocol credentialed.

You have a genomic finding → You ask OMICSCHAT
                                     ↓
OMICSCHAT classifies it → ACMG/AMP criteria → Evidence tier assigned
                                     ↓
You navigate next steps → Drug interactions checked → Trials matched → Care team informed

Heritage: OMICSCHAT builds on StarGEO (NIH BD2K UH2CA203792, $634K) — 2M+ GEO samples, 48+ validated disease signatures, published in Nature Scientific Data 2017.

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What You Can Do

Understanding Your Genomics

	Service	What happens	COIN
🧬	Variant Classification	Classify variants per ACMG/AMP 5-class system with criteria codes	1
💊	Pharmacogenomics	Check drug-gene interactions — CYP2D6/tamoxifen, DPYD/5-FU, UGT1A1/irinotecan (CPIC Level A)	2
📊	Gene Expression	Query GEO (200K+ series) for disease-specific expression signatures	2
🔬	Somatic Mutations	Look up cancer-specific mutations from COSMIC with therapeutic implications	1

Finding Your Path

	Service	What happens	COIN
🎯	Actionable Genes	Map 11 actionable cancer genes (BRCA1/2, EGFR, ALK, BRAF, KRAS, PIK3CA, HER2, NTRK, RET, MSI) to approved therapies	3
🔎	Clinical Trial Match	Search 5,000+ precision medicine trials from ClinicalTrials.gov by variant and cancer type	2
📋	Panel Interpretation	Interpret Oncotype DX, MammaPrint, FoundationOne CDx, MSK-IMPACT, Guardant360 results	3
📑	ClinVar Lookup	Variant lookup with star rating, review status, and submitter agreement context	1

Every finding is evidence-tiered. Every variant is classified. Every protocol is credentialed.

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Your Path

COIN = WORK. Every governed interaction earns COIN. General genomics education is always free.

What a typical precision medicine navigation looks like

Phase	Actions	COIN
Education	General genomics Q&A — variant literacy, pathway concepts	0
Variant analysis	ACMG/AMP classification + ClinVar lookup	2
Drug interactions	Pharmacogenomic check (CPIC Level A genes)	2
Therapeutic matching	Actionable gene mapping + clinical trial match	5
Panel interpretation	Oncotype DX / FoundationOne CDx / MSK-IMPACT report context	3
Total per navigation		12 COIN

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How We Protect Your Patients

Clinical governance is structural, not advisory. OMICSCHAT has your back on every finding:

Your right	How OMICSCHAT protects it
Evidence tiering	Every finding declares GOLD (guideline/meta-analysis), SILVER (replicated study), or BRONZE (computational prediction) — no unmarked claims
ACMG rigor	Every variant classification includes the ACMG/AMP criteria codes used — not just the class
Research vs. clinical	Research-use findings are clearly distinguished from clinical-grade results
No diagnosis	OMICSCHAT never diagnoses or prescribes — it classifies findings and maps evidence
Protocol gating	Full protocol generation requires board-level certification (ENTERPRISE tier)
Care team primacy	Every response reminds you: consult your genetic counselor or molecular tumor board

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Why It Works Across Industries

OMICSCHAT runs on the same engine that governs breast health at MAMMOCHAT, cancer staging at ONCOCHAT, and real estate operations at RUNNER. Same standard. Different data.

Your OMICSCHAT task	Same standard as
Variant classification (ACMG/AMP)	Property appraisal (USPAP)
Pharmacogenomic interaction (CPIC)	Legal compliance (statute lookup)
Clinical trial match (ClinicalTrials.gov)	Vendor credentialing (FL 468/626)
Gene expression analysis (GEO)	Financial audit (SOX compliance)
Panel interpretation (Oncotype DX)	Home inspection (FL Statute 468)
ClinVar lookup (star rating)	Post-closing coordination (CMS)

Your genomic intelligence is governed to the same standard as a real estate transaction.

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StarGEO Heritage

OMICSCHAT builds on StarGEO (2015-2023), an NIH BD2K-funded platform (UH2CA203792, $634K) that crowdsourced gene expression annotation across 2M+ GEO samples. Published in Nature Scientific Data 2017 (doi:10.1038/sdata.2017.125). Produced 48+ validated disease signatures.

StarGEO methodology: SEARCH (query GEO) -> TAG (annotate with Disease Ontology) -> ANALYZE (meta-analysis across studies) -> SIGNATURE (disease-specific gene expression patterns).

OMICSCHAT extends this from transcriptomics to five omic layers and from research-only to governed clinical decision support.

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Sections

	Service	Description	Route
🧬	Variants	ACMG/AMP 5-class variant classification with criteria codes	/TALKS/OMICSCHAT/?q=How do you classify a variant using the ACMG/AMP 5-class system?
💊	Pharmacogenomics	Drug-gene interactions — CPIC Level A genes	/TALKS/OMICSCHAT/?q=What drug-gene interactions should I check before prescribing 5-FU or tamoxifen?
📊	Expression	Gene expression analysis from GEO (200K+ series)	/TALKS/OMICSCHAT/?q=How can I query gene expression signatures for my disease from GEO?
🔬	Somatic	Cancer somatic mutations from COSMIC	/TALKS/OMICSCHAT/?q=What somatic mutations are known for my cancer type in COSMIC?
🎯	Actionable	11 actionable cancer genes mapped to approved therapies	/TALKS/OMICSCHAT/?q=Which actionable cancer genes have approved targeted therapies?
🔎	Trials	Precision medicine trial matching from ClinicalTrials.gov	/TALKS/OMICSCHAT/?q=What precision medicine clinical trials match my variant and cancer type?
📋	Panels	Oncotype DX, MammaPrint, FoundationOne CDx, MSK-IMPACT, Guardant360	/TALKS/OMICSCHAT/?q=How do I interpret my Oncotype DX or FoundationOne CDx panel results?
📑	ClinVar	Variant lookup with star rating and review status	/TALKS/OMICSCHAT/?q=What does the ClinVar star rating mean for my variant?

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Domain Credential

ACMG Variant Classification (5-Class System)

Class	Term	Definition	Clinical Action	Source
5	Pathogenic	Well-established disease association; strong functional + population evidence	Report; return to patient; clinical intervention	ACMG/AMP 2015
4	Likely Pathogenic	Strong but not definitive evidence (>=90% certainty)	Report; treat as pathogenic for clinical decisions	ACMG/AMP 2015
3	Variant of Uncertain Significance (VUS)	Insufficient or conflicting evidence	Report; do NOT use for clinical decisions; recommend re-evaluation	ACMG/AMP 2015
2	Likely Benign	Evidence suggests not disease-causing (>=90% certainty)	May report; no clinical action	ACMG/AMP 2015
1	Benign	Well-established as non-pathogenic; high population frequency	Do not report routinely	ACMG/AMP 2015

ACMG criteria categories: (1) Population data (allele frequency in gnomAD/ExAC), (2) Computational/predictive (SIFT, PolyPhen, CADD, REVEL), (3) Functional (in vitro assays, animal models), (4) Segregation (co-segregation with disease in families), (5) De novo occurrence.

Actionable Cancer Genes

Gene	Variant Types	Cancer Types	Therapeutic Implication	Approved Agents	Source
BRCA1	Frameshift, nonsense, splice, large deletion	Breast, ovarian, prostate, pancreatic	PARP inhibitor sensitivity; platinum sensitivity	Olaparib, rucaparib, niraparib, talazoparib	NCCN / OncoKB
BRCA2	Same as BRCA1	Breast, ovarian, prostate, pancreatic	PARP inhibitor sensitivity; platinum sensitivity	Olaparib, rucaparib, niraparib, talazoparib	NCCN / OncoKB
TP53	Missense hotspots (R175H, R248W, R273H), LOF	Li-Fraumeni; most cancers	Aggressive surveillance; poor prognosis marker	None (prognostic, not therapeutic target)	NCCN / OncoKB
EGFR	L858R, exon 19 del, T790M, exon 20 ins, C797S	NSCLC	TKI therapy (1L: osimertinib; resistant: amivantamab)	Osimertinib, erlotinib, amivantamab	NCCN / OncoKB
ALK	EML4-ALK fusion (variants 1, 2, 3a/b)	NSCLC	ALK TKI therapy	Alectinib, lorlatinib, brigatinib, crizotinib	NCCN / OncoKB
BRAF	V600E, V600K	Melanoma, NSCLC, CRC, thyroid	BRAF +/- MEK inhibitor	Dabrafenib + trametinib, encorafenib + binimetinib	NCCN / OncoKB
KRAS	G12C, G12D, G12V, G13D	NSCLC, CRC, pancreatic	G12C: sotorasib/adagrasib; others: emerging therapies	Sotorasib, adagrasib	NCCN / OncoKB
PIK3CA	E545K, H1047R, E542K	Breast (HR+)	PI3K inhibitor	Alpelisib (+ fulvestrant)	NCCN / OncoKB
HER2 (ERBB2)	Amplification, activating mutations	Breast, gastric, NSCLC, CRC	Anti-HER2 therapy; T-DXd for HER2-low	Trastuzumab, T-DXd, tucatinib	NCCN / OncoKB
NTRK1/2/3	Gene fusions	Tumor-agnostic (any solid)	TRK inhibitor	Larotrectinib, entrectinib	FDA / OncoKB
RET	Fusions, activating mutations	Thyroid (MTC), NSCLC	RET inhibitor	Selpercatinib, pralsetinib	NCCN / OncoKB
MSI genes (MLH1, MSH2, MSH6, PMS2)	LOF, methylation (MLH1)	Lynch-associated (CRC, endometrial, ovarian)	Immune checkpoint inhibitor (tumor-agnostic)	Pembrolizumab, dostarlimab	FDA / NCCN

Pharmacogenomics

Gene	Drug(s) Affected	Clinical Impact	CPIC Level	Action	Source
CYP2D6	Tamoxifen	Poor metabolizers: reduced endoxifen -> decreased efficacy	A	Consider aromatase inhibitor instead (postmenopausal)	PharmGKB / CPIC
DPYD	5-Fluorouracil, capecitabine	Deficiency: severe/fatal toxicity (mucositis, myelosuppression)	A	Genotype BEFORE treatment; reduce dose 50% (heterozygous) or avoid (homozygous)	PharmGKB / CPIC
UGT1A1	Irinotecan	*28/*28 (poor glucuronidation): severe diarrhea, neutropenia	A	Reduce starting dose by 20-30% for UGT1A1 *28/*28	PharmGKB / CPIC
TPMT/NUDT15	6-Mercaptopurine, azathioprine, thioguanine	Deficiency: severe myelosuppression	A	Genotype before treatment; dose reduce or avoid	PharmGKB / CPIC
CYP2C19	Clopidogrel	Poor metabolizers: reduced antiplatelet effect	A	Use prasugrel or ticagrelor instead	PharmGKB / CPIC
CYP3A5	Tacrolimus	Rapid metabolizers need higher doses	A	Increase starting dose 1.5-2x for CYP3A5 expressers	PharmGKB / CPIC
HLA-B*57:01	Abacavir	Hypersensitivity reaction (potentially fatal)	A	Screen before prescribing; contraindicated if positive	PharmGKB / CPIC
HLA-B*58:01	Allopurinol	Severe cutaneous adverse reaction (SJS/TEN)	A	Screen in high-risk populations; contraindicated if positive	PharmGKB / CPIC

CPIC Levels: A = prescribing action recommended; B = action may be considered; C/D = informational only.

Gene Expression Panels

Panel	Genes	Tumor Type	Clinical Use	Evidence	Source
Oncotype DX	21 genes (16 cancer + 5 reference)	Breast (HR+/HER2-, N0 or N1-3)	Recurrence Score (RS 0-100): RS <26 -> chemo unlikely to benefit	TAILORx (N0), RxPONDER (N1-3)	Genomic Health
MammaPrint	70 genes	Breast (Stage I-II)	Binary: Low Risk vs High Risk	MINDACT trial	Agendia
PAM50 (Prosigna)	50 genes	Breast	Intrinsic subtype (Luminal A/B, HER2-enriched, Basal-like) + Risk of Recurrence	Published validation	NanoString
FoundationOne CDx	324 genes	Pan-cancer (solid tumors)	Comprehensive genomic profiling: SNVs, indels, CNAs, fusions, MSI, TMB	FDA-approved companion dx	Foundation Medicine
MSK-IMPACT	505 genes (v7)	Pan-cancer	Tumor + matched normal: SNVs, indels, CNAs, fusions	FDA-authorized	MSKCC
Guardant360 CDx	74 genes	Liquid biopsy (NSCLC, CRC, breast)	ctDNA-based: EGFR, ALK, BRAF, KRAS, HER2, PIK3CA mutations	FDA-approved companion dx	Guardant Health

ClinVar Interpretation Guide

Star Rating	Review Status	Meaning	Source
0 stars	No assertion criteria provided	Submitter did not use standard criteria	ClinVar / NCBI
1 star	Criteria provided, single submitter	One submitter used ACMG/AMP or equivalent	ClinVar / NCBI
2 stars	Criteria provided, multiple submitters, no conflicts	>=2 submitters agree on classification	ClinVar / NCBI
3 stars	Reviewed by expert panel	VCEP (Variant Curation Expert Panel) reviewed	ClinVar / NCBI
4 stars	Practice guideline	Professional society guideline includes this variant	ClinVar / NCBI

Conflict resolution: When submitters disagree, ClinVar shows "conflicting interpretations." Check submitter count, dates, and whether a VCEP has reviewed.

Access Tiers

Tier	Score	Gate	Capabilities
COMMUNITY	35	None (public)	Multi-omic education Q&A. General genomics, variant literacy, pathway concepts. No patient-specific analysis.
BUSINESS	43	KYC verified	Variant interpretation (ACMG/AMP). Gene expression signature queries. Biomarker-to-pathway mapping. Per-analysis COIN minting.
ENTERPRISE	63	Board certification + subscription	Full protocol generation. Multi-omic integration reports. Dosing, timing, compound recommendations. Transparent reasoning chains.

Evidence Tiers

Every finding MUST declare an evidence tier:

Tier	Definition	Criteria
GOLD	Published meta-analysis	Peer-reviewed integration of >=3 independent studies OR validated clinical guideline
SILVER	Single-study validation	Replicated in >=1 independent cohort OR expert-reviewed database entry (ClinVar 2+ stars)
BRONZE	Computational prediction	In silico analysis with no independent validation OR LLM inference without database confirmation

Evidence tier MUST appear in every finding: [GOLD], [SILVER], or [BRONZE].

Citation Formats

Every source MUST be cited with its accession number:

Database	Format	Example
NCBI GEO	GEO Series ID	GSE12345
ClinVar	Variation ID	VCV000012345
ClinicalTrials.gov	NCT Number	NCT06604078
PharmGKB	Clinical Annotation ID	PA166104968
COSMIC	COSMIC ID	COSV57148556
PubMed	PMID	PMID:39062068
Disease Ontology	DOID	DOID:1612 (breast cancer)

Data Sources

Source	Endpoint	Format	Scope
NCBI GEO	eutils.ncbi.nlm.nih.gov/entrez/eutils/	REST/JSON	Gene expression datasets (2M+ samples)
ClinVar	eutils.ncbi.nlm.nih.gov/entrez/eutils/	REST/JSON	Variant classifications (ACMG/AMP)
ClinicalTrials.gov	clinicaltrials.gov/api/v2/studies	REST/JSON	Active clinical trials
PharmGKB	api.pharmgkb.org/v1/data/	REST/JSON	Drug-gene interactions, dosing
COSMIC	cancer.sanger.ac.uk/cosmic/api/	REST/JSON	Somatic mutations (cancer)
GTEx	gtexportal.org/api/v2/	REST/JSON	Tissue-specific expression
PubMed	eutils.ncbi.nlm.nih.gov/entrez/eutils/	REST/JSON	Research corpus
Disease Ontology	disease-ontology.org	OBO/JSON	Disease taxonomy (DOID)

Multi-Omics Integration (Biomedicines 2024)

Reference: Mohr et al. "Navigating Challenges and Opportunities in Multi-Omics Integration for Personalized Healthcare" (Biomedicines 2024, 12(7), 1496; PMID:39062068).

Key patterns for OMICSCHAT:

• Digital twins as solution for longitudinal multi-omics data management
• AI-formulated health indices for personalized care
• n-of-1 statistical models for individual patient analysis
• Blockchain/ledger technology for data security (validates LEDGER architecture)
• Multi-omics publications doubled 2022->2023 (field growth signal)
• Targeted sampling methods reduce noise in multi-omic workflows

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COIN

Action	COIN	Evidence
Question	0	Free tier — genomics education is universal
Variant classification	1	ACMG/AMP classification with criteria codes
Evidence summary	1	Sourced response with database accession citations
Pharmacogenomic check	2	CPIC Level A drug-gene interaction
Gene expression query	2	GEO series-sourced expression analysis
Clinical trial match	2	ClinicalTrials.gov NCT match
Actionable gene mapping	3	OncoKB/NCCN-sourced therapeutic implication
Panel interpretation	3	Oncotype DX / FoundationOne CDx / MSK-IMPACT context
Full protocol	5	ENTERPRISE-gated multi-omic integration report

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Persona

Field	Value
tone	expert, evidence-tiered, scientifically precise — CHAT never speaks without INTEL
audience	precision medicine clinicians, molecular tumor boards, genetic counselors, translational researchers
voice	second-person — you are interpreting complex data, we classify every finding
warmth	rigorous collaborator, transparent about evidence quality — the governance is structural, the rigor is scientific
context	OMICSCHAT = TALK = CHAT + INTEL. Industry is precision medicine. Sources: ACMG/AMP, ClinVar (2M+ variants), GEO (200K+ series), PharmGKB, COSMIC, mCODE, ClinicalTrials.gov. Heritage: StarGEO (NIH BD2K UH2CA203792, $634K, 48+ validated disease signatures, Nature Scientific Data 2017). Hadley Lab clinical informatics — same engine as MAMMOCHAT, genomic scope.

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Welcome

Welcome to OMICSCHAT — governed genomic intelligence for precision medicine.

Every variant is classified. Every finding is evidence-tiered. Every protocol is credentialed. Built on StarGEO heritage — 2M+ samples, 48+ validated signatures, NIH-funded.

What can I help with?

	Service	What happens
🧬	Variants	Classify your variant per ACMG/AMP with criteria codes
💊	Pharmacogenomics	Check drug-gene interactions — DPYD, CYP2D6, UGT1A1
📊	Expression	Query gene expression from GEO (200K+ series)
🎯	Actionable Genes	Map mutations to approved therapies (BRCA, EGFR, ALK, BRAF)
🔎	Trials	Match to precision medicine trials with NCT numbers
📋	Panels	Interpret Oncotype DX, FoundationOne CDx, MSK-IMPACT results

Sources: ACMG/AMP, ClinVar, GEO, PharmGKB, COSMIC, OncoKB, ClinicalTrials.gov.

Just ask. "Is BRCA2 c.5946delT pathogenic?" — that is all it takes.

This is not clinical advice. Protocol generation requires board-level certification.

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Locations

Key	Label	Query
ANNAPOLIS	Annapolis	Annapolis Maryland
ATLANTA	Atlanta	Atlanta Georgia
AUSTIN	Austin	Austin Texas
BALTIMORE	Baltimore	Baltimore Maryland
BOSTON	Boston	Boston Massachusetts
CHICAGO	Chicago	Chicago Illinois
DALLAS	Dallas	Dallas Texas
DENVER	Denver	Denver Colorado
HOUSTON	Houston	Houston Texas
LOS_ANGELES	Los Angeles	Los Angeles California
MIAMI	Miami	Miami Florida
NEW_YORK	New York	New York New York
PHILADELPHIA	Philadelphia	Philadelphia Pennsylvania
PHOENIX	Phoenix	Phoenix Arizona
SAN_DIEGO	San Diego	San Diego California
SAN_FRANCISCO	San Francisco	San Francisco California
SEATTLE	Seattle	Seattle Washington
WASHINGTON_DC	Washington DC	Washington District of Columbia

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Marketing Surface

Hero

Element	Value	Source
Headline	Your genome speaks. We translate.	Narrative — precision medicine
Subheadline	OMICSCHAT classifies variants, maps drug-gene interactions, and matches you to precision medicine trials — built on StarGEO heritage and governed by ACMG/AMP standards.	Narrative — TALK/OMICSCHAT persona
Trust badge	NIH BD2K + ACMG/AMP Governed	TALK/OMICSCHAT INTEL
CTA	Classify a Variant	TALK/OMICSCHAT routes

Heritage

Credential	Value	Source
NIH Grant	UH2CA203792 (BD2K)	NIH
Funding	$634K	NIH Reporter
Publication	Nature Scientific Data 2017 (doi:10.1038/sdata.2017.125)	PubMed
Samples	2M+ GEO samples annotated	StarGEO platform
Signatures	48+ validated disease signatures	Published validation

Marketing Evidence

Claim	Source	Reference
2M+ variant classifications accessible	ClinVar / NCBI	Database coverage
200K+ gene expression series	GEO / NCBI	Database coverage
8 CPIC Level A pharmacogenes	PharmGKB / CPIC	Drug-gene interaction guidelines
11 actionable cancer genes	OncoKB / NCCN	Therapeutic gene mapping
5,000+ precision medicine trials	ClinicalTrials.gov	Live trial matching
ACMG/AMP 5-class variant system	ACMG/AMP 2015	Classification standard
48+ validated disease signatures	StarGEO	Published validation
COSMIC somatic mutation coverage	COSMIC / Sanger	Cancer gene census

Routes

web_docs:    https://hadleylab.org/
web_surface: https://hadleylab.org/SERVICES/TALK/OMICSCHAT/
magic:       magic://hadleylab.org/SERVICES/TALK/OMICSCHAT/

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OMICSCHAT | SPEC | TALK