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Record W4415588730 · doi:10.1101/2025.10.23.683559

Design principles underlying nearly-homeostatic biological networks

2025· preprint· W4415588730 on OpenAlexafffund
Zhe Tang, David R. McMillen

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2025
Typepreprint
Language
FieldBiochemistry, Genetics and Molecular Biology
TopicGene Regulatory Network Analysis
Canadian institutionsUniversity of Toronto
FundersNatural Sciences and Engineering Research Council of Canada
KeywordsProcess (computing)Design elements and principlesSystems designState (computer science)Complex systemBiological networkDesign processWork (physics)

Abstract

fetched live from OpenAlex

Abstract A nearly-homeostatic system like body temperature maintenance keeps the steady state system output like internal body temperature within a narrow range, regardless of different persistent levels of environmental perturbations like external temperatures. Nearly-homeostatic systems can be implemented to guarantee performance of a therapeutic device in different patient contexts. Exploration of different near-homeostasis-supporting architectures to satisfy different design requirements is necessary, but methods for doing so in a fast and comprehensive manner remain elusive. We have identified two constrained optimization approaches to find near-homeostasis supporting architectures 10 to 100 times faster than brute-force search. Once such architectures are found, characterizing the underlying mechanisms of near-homeostasis is hindered by the very cumbersome and limited nature of traditional statistical analysis approaches. We have developed two levels of “inverse homeostasis plots”, and used them to identify two novel near-homeostasis mechanisms that tolerate much higher undesired basal expression and much higher undesired first order degradation rates than previously characterized near-homeostasis mechanisms. Teaser A comprehensive toolset was developed for much faster discovery and much more comprehensive analysis of near-homeostasis-supporting architectures.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Theoretical or conceptual · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.003
Threshold uncertainty score0.012

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0030.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.039
GPT teacher head0.248
Teacher spread0.210 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designTheoretical or conceptual
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2025
Admission routes2
Has abstractyes

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