What question did this study set out to answer?

The study aims to evaluate the statistical properties of 20,158 human proteins based on their geometric scores to identify druggable and allosteric proteins.

May 15, 2026Open Access

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Genesis Human Proteome Scan v2: Full Statistical Analysis of Lo-Shu/Markov-Fiedler Geometric Scores across 20,158 Human Proteins — Score Distributions, Population Thresholds, Allosteric Prioritization, and Novel MTRNR2L/Metallothionein Findings

Key Points

The study aims to evaluate the statistical properties of 20,158 human proteins based on their geometric scores to identify druggable and allosteric proteins.
Analyzed 20,158 human proteins using the Lo-Shu/Markov-Fiedler geometric framework.
Calculated drug score, allo score, and spectral gap metrics, identifying specific thresholds and rankings for proteins.
Corrected for size confound using OLS residualization.
Drug score mean=0.992 with 99.8% identified as draggable, 37 classified as borderline.
Allo score mean=-24.4, with a top-1% threshold of -7.60 for 203 proteins.
Metallothionein family dominates spectral ranking with scores between 0.28-0.38, and MTRNR2L peptides leading in allosteric ranking.

Abstract

Full statistical analysis of the Genesis Human Proteome Scan. 20, 158 human proteins (AlphaFold v4, C-alpha only) analyzed with the Lo-Shu/Markov-Fiedler geometric framework (validated AUC=0. 882; DOI: 10. 5281/zenodo. 20153617). Key results: (1) Drug score: mean=0. 992, 99. 8% DRUGGABLE, 37 BORDERLINE. (2) Allo score: mean=-24. 4; top-1% threshold=-7. 60 (n=203 proteins). (3) Spectral gap (Fiedler lambda3-lambda2): mean=0. 017; top-1% threshold=0. 122 (n=202). Novel findings: Metallothionein family (MT1A/B/E/F/G/H/L/M/X, MT2A, MT4) dominates spectral boundary ranking (spectralgap 0. 28-0. 38), consistent with two-domain alpha/beta cluster architecture. MTRNR2L/Humanin-like peptides top the allosteric ranking. Q8N339 (MT1M) is a dual allosteric+Fiedler signal candidate. BORDERLINE proteins include DYNLL1, CYCS, TXN, Oncomodulins. Size confound (rho=-0. 683 raw; -0. 119 after OLS residualization) reported and corrected. All 4 manuscript figures and full score tables included.

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Genesis Human Proteome Scan v2: Full Statistical Analysis of Lo-Shu/Markov-Fiedler Geometric Scores across 20,158 Human Proteins — Score Distributions, Population Thresholds, Allosteric Prioritization, and Novel MTRNR2L/Metallothionein Findings

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Abstract

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