Assay coverage reshapes metabolic diagnosis and the interpretation of pathway disturbance
- 1Moscow State University
Abstract
Metabolic profiles are used to quantify disturbance, classify disease and infer biochemical function, yet these endpoints retain different information. We combine secondary analysis of 386 metabolites in six Arabidopsis thaliana mutation accumulation lines, known-disease classification in 129 public human metabolic-disease profiles, and an analytically solvable kinetic model. A conditional occupancy model separates annotation-bin breadth from hit count and measured bin sizes: the plant low-versus-high fitness comparison changes from a two-sided exact permutation p = 0.10 to p = 0.30 after calibration. Unsigned metabolite profiles achieve mean macro recall of 0.911 and 0.895 in separate EDTA and heparin subsets, compared with 0.624 and 0.382 for a burden baseline. However, controlled loss of 50% of held-out measurements reverses representation ranking in heparin, giving signed profiles a recall advantage of 0.108 with a conditional bootstrap interval of 0.063-0.155. A spectral decomposition identifies the within-pathway contrasts attenuated by smoothing. The kinetic model then shows that lower concentration and faster relaxation can coexist with reduced desired product flux, while a null-space criterion states when observations identify a metabolic task. The results connect assay coverage, diagnostic information and functional identifiability. Human performance is internally validated, and the kinetic predictions remain uncalibrated to patients.
Related
- Cross-feeding reshapes interactions between antibiotic stressors through metabolic feedbacks
- Redox oscillation frequency reshapes antibiotic resistance-gene expression through metabolic and ecological selection in a freshwater community
- Severe salinity reshapes the ionomic and metabolic profiles of quinoa leaves and seeds in a genotype-dependent manner
- Defining the Oxysterolome: Analytical Coverage, Metabolic Connectivity, and Biological Validation
- The clinical spectrum of MECP2 variants in males: a multicenter Turkish cohort of 22 probands, with implications for diagnosis and variant interpretation
BibTeX
@misc{fontaine2026assay,
title = {{Assay coverage reshapes metabolic diagnosis and the interpretation of pathway disturbance}},
author = {C. Fontaine and I. Smirnov},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.03.756464},
url = {https://www.biorxiv.org/content/10.64898/2026.10.03.756464v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Assay coverage reshapes metabolic diagnosis and the interpretation of pathway disturbance
AU - C. Fontaine
AU - I. Smirnov
PY - 2026
DA - 2026/10/03
PB - bioRxiv
DO - 10.64898/2026.10.03.756464
UR - https://www.biorxiv.org/content/10.64898/2026.10.03.756464v1
AB - Metabolic profiles are used to quantify disturbance, classify disease and infer biochemical function, yet these endpoints retain different information. We combine secondary analysis of 386 metabolites in six Arabidopsis thaliana mutation accumulation lines, known-disease classification in 129 public human metabolic-disease profiles, and an analytically solvable kinetic model. A conditional occupancy model separates annotation-bin breadth from hit count and measured bin sizes: the plant low-versus-high fitness comparison changes from a two-sided exact permutation p = 0.10 to p = 0.30 after calibration. Unsigned metabolite profiles achieve mean macro recall of 0.911 and 0.895 in separate EDTA and heparin subsets, compared with 0.624 and 0.382 for a burden baseline. However, controlled loss of 50% of held-out measurements reverses representation ranking in heparin, giving signed profiles a recall advantage of 0.108 with a conditional bootstrap interval of 0.063-0.155. A spectral decomposition identifies the within-pathway contrasts attenuated by smoothing. The kinetic model then shows that lower concentration and faster relaxation can coexist with reduced desired product flux, while a null-space criterion states when observations identify a metabolic task. The results connect assay coverage, diagnostic information and functional identifiability. Human performance is internally validated, and the kinetic predictions remain uncalibrated to patients.
ER -