Every number comes from an engine. Here is every engine.

Given the evidence criteria a curator has attributed to a germline variant, is that variant pathogenic, benign, or of uncertain significance? Two independent models run, and where they disagree the disagreement is reported rather than averaged.

How chemically different are two amino acids from one another, on the published composition, polarity and volume distance?

Does a protein sequence’s dipeptide composition predict that it will be stable in vitro?

What starting warfarin dose do a patient’s demographics and CYP2C9 / VKORC1 genotype predict, under the published consortium algorithm?

Does an in-silico pathogenicity score support or oppose a variant being damaging, and at what evidence strength? A score inside the indeterminate band yields no criterion at all.

Is a variant too common in the general population to be causing a given rare disease?

What drug-metabolizer phenotype does a patient’s star-allele diplotype imply, and what does the published prescribing guideline say to do about it?

What are a protein sequence’s basic physical constants: molecular weight, isoelectric point, molar absorbance at 280 nm, hydropathy, and aliphatic index?

From a SMILES string, what are a molecule’s drug-likeness descriptors, and which of its rings does the standard aromaticity model perceive as aromatic?

How strong is the published literature behind a claim, given the best study design available, how many independent papers corroborate it, how recent they are, and whether any refute it?

How much confidence does the archived clinical record support for a gene and variant, given ClinVar review status, agreement between submitters, and quote-grounded literature? This gathers evidence; it does not classify the variant.

How much clinical evidence exists that a drug has been studied for an indication, by trial phase, breadth and results? This measures how much was studied, never whether the drug works.

Deterministic perfusion-limited physiologically-based pharmacokinetic simulation of a compound through the real circulatory topology (venous → lung → arterial → organs, gut/spleen draining portally through the liver), giving per-organ and plasma concentration-time curves plus non-compartmental PK. Vascular states are blood-referenced and converted to plasma for reporting through an explicit blood:plasma ratio (default 1). Tissue partitioning uses the COMPLETE Poulin & Theil tissue-composition method (phospholipid terms, the fu_p/fu_t binding correction, and the separate vegetable-oil equation for adipose) on the human composition table; it is systematically low for moderate-to-strong bases, which the result flags say. Hepatic elimination can be parameterised three ways, most specific first: saturable Michaelis-Menten on unbound drug (Vmax/Km), unbound-driven linear intrinsic clearance (well-stirred), or a whole-organ clearance. Compound ADME inputs are supplied and are NOT derived here; physiology, the ODE solution and every reported metric are computed. Research use — it predicts exposure under the stated model, it does not establish a dose.

Scales the whole-body simulation to a subject’s covariates (metaboliser activity through the fraction metabolised fm, Child-Pugh hepatic grade, renal function, body weight) and generates a SEEDED virtual population whose 5th/50th/95th-percentile exposure bands are reproducible from the seed alone. Also computes therapeutic-window residence. Covariates scale clearance only; between-subject parameters are currently sampled INDEPENDENTLY, so the bands do not represent covariate correlation.

Simulates a perpetrator compound’s own pharmacokinetics, then re-simulates the victim under the resulting time-varying hepatic clearance, reporting AUC and Cmax ratios and an FDA-threshold classification. The same clearance-scaling contract carries a star-allele diplotype through the CPIC activity score to a whole-body exposure prediction. The interaction is applied through the fraction of the victim’s hepatic clearance the affected enzyme carries (fm), so the AUC ratio is bounded by 1/(1−fm) as inhibition becomes complete rather than rising without limit. fm defaults to 1 — the whole hepatic clearance responding — which is an upper bound unless a victim-specific fm is supplied.