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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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Research integrity
Consensus categoriesMeta-epidemiology (narrow)
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.460
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.001
Meta-epidemiology (narrow)0.0020.002
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0010.002
Science and technology studies0.0010.001
Scholarly communication0.0010.000
Open science0.0020.003
Research integrity0.0030.002
Insufficient payload (model declined to judge)0.0000.000

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; both teacher heads agree on what is shown here.

Study designBench or experimental
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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