pg-phenotype

Phenotypes in the context of a pedigree, as an extension of pedigree-graph: a Rust core with Python and R bindings. Relationships and kinship come from pedigree-graph's core; each method is a module on top.

Python

import pg_phenotype as pgp
from pg_phenotype import pafgrs

ped = pgp.Pedigree(pedigree)  # validated once, for every method
trait = pgp.Trait(dx, kind="binary")  # one value per pedigree row
prep = pafgrs.prepare(ped, ndegree=2)  # once per pedigree and degree
cip = pafgrs.Cip(ages, cip_values)  # K is the last value
cip = pafgrs.Cip.from_aalen_johansen(age, status, entry=entry_age)  # or estimate it
scores = pafgrs.score_univariate(prep, trait, age=dx_age, cip=cip, h2=0.4)
scores.est, scores.var, scores.n_relatives, scores.metadata

both = pafgrs.score_bivariate(prep, (t1, t2), age=(a1, a2), cip=(c1, c2), h2=(0.4, 0.6), rg=0.5)

• pedigree: columns id, mother, father (-1 or NA when missing) and optional twin, sex (0 female, 1 male), as a polars or pandas frame or a mapping of arrays. It is validated by pedigree-graph's rules.
• Pedigree(pedigree) validates the columns once. Every method takes a Pedigree or the columns, which it validates for that call alone. A Pedigree helps when you prepare again (another ndegree or set of probands) or run several methods, or mate_correlation several times, on one pedigree. Scoring many traits needs only the prep.
• Trait(values, kind=None): one phenotype column on the pedigree's rows, NA where unknown. The kind is continuous, binary, ordinal or categorical, inferred when unambiguous.
• PA-FGRS takes a binary trait. age is the onset age for a case and the last observed age for a control; a control without an age is unobserved and counted.
• probands= restricts the scored rows; relatives are drawn from the whole pedigree. Output is one record per proband in input-row order.
• configure_threads(n) or PG_PHENOTYPE_THREADS sets the thread budget (default 1). Results are identical for every budget.

Errors are pg_phenotype.ValidationError, ParameterError and ResourceError, each with a stable .code and .fields.

CIP from data

Cip.from_aalen_johansen(age, status, entry=None) estimates the CIP with the Aalen-Johansen estimator: age at onset, death or last observation, status 0 censored, 1 case, 2 death (a competing risk), and entry the age observation starts (late entry; entry < t <= age is at risk). The result is a Cip with interpolation="step": between case ages it holds the last estimate, where Cip(ages, cip) interpolates linearly. K is its last value. For a CIP per sex, pass each sex's rows; scoring takes one CIP per trait (ADR 0010).

Assortative mating

from pg_phenotype.assortative import mate_correlation

res = mate_correlation(ped, [pgp.Trait(liab), pgp.Trait(dx)], stratum=birth_decade, bootstrap=1000, seed=1)
cell = res.cell(0, 1)  # mothers' trait 0 x fathers' trait 1
cell.primary.value, cell.primary.ci, cell.primary.permutation.p
cell.stratified.result.value  # within birth-decade strata
res.within_person["mothers"]

The Mate Correlation is the correlation between the mother's and the father's value of a trait over a pedigree's Mating Pairs. Each cell uses the estimators its trait kinds call for (Pearson, tetrachoric, polychoric, biserial or polyserial, with their closed-form companions), a Mate Network sandwich SE, an optional Mate Network bootstrap, and a sequential father-permutation p-value. docs/assortative-mating.md describes the inputs, rules and every result field, and docs/assortative-mating-design.md explains the design.

Tetrachoric correlation

from pg_phenotype.correlation import tetrachoric

res = tetrachoric(x, y)  # paired 0/1 values, NA dropped
res = tetrachoric(table=[[n00, n01], [n10, n11]])  # rows by the x level
res.value, res.se, res.ci, res.boundary, res.reason

The Mate Correlation's tetrachoric fit on one table: two-step maximum likelihood, a boundary flag, and the two-step sandwich SE with each pair its own cluster (ADR 0006).

Parent-offspring regression

from pg_phenotype.regression import parent_offspring

res = parent_offspring(ped, pgp.Trait(liab), stratum=generation)
fit = res.pooled.midparent  # also .mother, .father
fit.slope, fit.se, fit.ci, fit.p, fit.se_ols, fit.n, fit.n_mate_networks
res.strata[2].father  # children with stratum label 2

The OLS line of each child's trait on its midparent's, its mother's and its father's value, pooled and within strata of the child. se is the cluster-robust sandwich over the whole pedigree's Mate Networks (a parent in no Mating Pair is a network of its own), with a Wald p and ci; se_ols is the plain OLS SE. Slopes are raw: under random mating and no environment shared by parent and child, the midparent slope estimates h2 and a single-parent slope h2/2. The sandwich SE needs many networks (ADR 0007).

Relative-Pair Correlation

from pg_phenotype import relative_pairs

res = relative_pairs.correlation(ped, pgp.Trait(dx, kind="binary"), categories=["MZ", "FS", {"PO": ["MO", "FO"]}, "1C"])
fs = res.cell("FS")
fs.primary.value, fs["phi"].value, fs.n, fs.n_dropped, fs.concordance
res.cell("PO").table, res.cell("PO").roles  # rows by offspring; ("offspring", "parent")

One cell per category code or named Category Group (default: every pedigree-graph category up to degree 3). A continuous trait gets Pearson's r; a binary one the tetrachoric (primary) and phi. A symmetric category's pairs enter in both orders, so its correlation is intraclass and does not depend on row order; a directed category's enter once, in its roles' order. Pairs are reduced as pedigree-graph finds them and never stored (memory_budget_bytes= bounds the accumulators). There is no minimum pair count and no SE yet: relative pairs share people, and the cluster design waits on a calibration study (ADR 0009).

Rows and alignment

A Pedigree keeps its input's row order: row i of the Pedigree is row i of the columns it was built from. Traits, ages, strata and probands are matched to it by position, and the caller aligns them. Move values from another table onto the Pedigree's rows with align:

dx = ped.align(pheno["id"], pheno["dx"])  # NaN where a row has no value
trait = pgp.Trait(dx, kind="binary")
rows = ped.rows(pheno["id"])  # the row of each id, for values align does not take

dx <- pedigree_align(ped, pheno$id, pheno$dx)  # NA where a row has no value
rows <- pedigree_rows(ped, pheno$id)  # 1-based

Each id must be a Pedigree row's (unknown_id) and appear once (duplicate_lookup_id). The first call builds an id index that the Pedigree keeps: 12 bytes per row.

Warning: Validation proves that the pedigree is well formed, not that a trait belongs to its rows. A trait shuffled by a sort or a join passes every check and gives a plausible, wrong result.

R

library(pgphenotype)

ped <- pedigree(ped_df)
dx <- trait(ped_df$dx, kind = "binary")
prep <- pafgrs_prepare(ped, ndegree = 2L)
cip <- pafgrs_cip(ages, cip_values)
cip <- pafgrs_cip_aalen_johansen(age, status, entry = entry_age)  # or estimate it
scores <- pafgrs_score_univariate(prep, dx, age = ped_df$dx_age, cip = cip, h2 = 0.4)
both <- pafgrs_score_bivariate(prep, list(t1, t2), ages = list(a1, a2),
                               cips = list(c1, c2), h2 = c(0.4, 0.6), rg = 0.5)
am <- assortative_mate_correlation(ped, list(trait(ped_df$liab), trait(ped_df$dx)),
                                   stratum = ped_df$birth_decade, bootstrap = 1000, seed = 1)
tc <- correlation_tetrachoric(ped_df$dx1, ped_df$dx2)  # or table = matrix(...)
po <- regression_parent_offspring(ped, trait(ped_df$liab), stratum = ped_df$generation)
rp <- relative_pairs_correlation(ped, trait(ped_df$dx, kind = "binary"),
                                 categories = list("MZ", "FS", PO = c("MO", "FO")))

The R package runs the same core as Python and returns the same scores bit for bit. pedigree() keeps the storage type of its ids (integer, double or bit64::integer64) for every result; length(ped) and ped$ids give its rows. Errors are conditions of class pgphenotype_error (with pgphenotype_validation_error and friends) carrying $code and $fields, positions 1-based.

Correctness (PA-FGRS)

• Rust against NumPy reference cores (fitACE's, verbatim) given the same covariance and order: within 1e-10.
• Against BioPsyk/PAFGRS's own pa_fgrs on stored fixtures: within 1e-10 (1.1e-15 observed).
• Every kinship value bit-identical to pedigree-graph's pair_kinship.

Correctness (Aalen-Johansen CIP)

• Against simACE's _aalen_johansen on 18 pipeline cases with continuous ages: bit-identical. With whole-year ages simACE also counts a person at risk at the age they enter; moving entries one ulp earlier makes it bit-identical again (docs/gates/aalen-johansen).
• Against R survival's survfit on all 24 cases: within 4.5e-14 relative.

Correctness (assortative mating)

• Against pedsum #13 at 142adf3 on 74 stored cases (28 fixtures, pedsum's own benchmark pedigrees at 10^4 pairs, and 40 random pedigrees), every count, reason, flag and p-value is identical. Closed-form estimates agree within 4.5e-15, and latent ones within 3.2e-10, inside Brent's 1e-7 tolerance. One case differs on float noise in pedsum. The gate report has the details.
• On pedsum's benchmark pedigrees at 10^4 to 10^6 pairs and up to 12 threads, pg-phenotype's median wall time and peak memory are at most 0.994 and 0.981 of pedsum's (benchmark report).
• The SciPy and C-library functions pedsum calls are ported bit for bit (ADR 0005).

Correctness (parent-offspring regression)

• Against simACE 6355ffa on six simulated pedigrees, slope, intercept, r and the OLS SE are bit-identical on simACE's float64 paths. Its validation, which forms the midparent in float32, differs by up to 3.1e-7 relative. Every case simACE leaves undefined is one of its floors (10 trios, 100 offspring, parent SD 1e-10) or undefined here too (gate report).
• Against a NumPy/SciPy reference with its own union-find networks and a matrix-form sandwich (tests/oracle/po_regression_reference.py), on random pedigrees with remating, missing and external parents: every field to 1e-10.

Correctness (Relative-Pair Correlation)

• Against a reference on pedigree-graph's own pair list (tests/oracle/relative_pairs_reference.py: NumPy double-entry Pearson and phi, correlation.tetrachoric on the doubled table), on random inbred pedigrees with twins and on three simACE small_test reps: every count equal, Pearson and phi within 1e-12, the tetrachoric identical.
• Against simACE 6355ffa on those reps: every pair count and table equal; on MO and FO, Pearson and phi within 1e-14 and the tetrachoric within 1.2e-8. Symmetric categories differ by design, by up to 3.4e-3 at a thousand pairs or more (gate report).

Design decisions are in docs/adr/; vocabulary in CONTEXT.md.

Development

pixi run test        # rebuilds the extension with test hooks, then pytest (no slow tests)
pixi run test-all    # the same with the slow tests, as CI runs it
pixi run test-rust
pixi run -e r r-test
pixi run test-against-pg ../pedigree-graph   # every suite against a pg checkout

To release a version, follow How to release pg-phenotype.