Oxphos
Exercise interventions offer profound systemic benefits, yet patient adherence remains a major clinical hurdle.
Core trick
Re-processes raw metabolomics spectra to recover a metabolite missing from released feature tables, then filters designed analogs through open ADMET and target databases.
Description
Exercise interventions offer profound systemic benefits, yet patient adherence remains a major clinical hurdle. Recent reports identify Lac-Phe (N-lactoyl-phenylalanine) as an exercise-induced metabolite driving appetite suppression and fat loss; however, it is entirely absent from every released feature table in the MoTrPAC exercise atlas. Using Claude Science, this project orchestrated the re-analysis of raw metabolomics data to map Lac-Phe dynamics across 19 tissues.
The signal was successfully recovered from raw spectra, revealing robust training-induced elevations—including a previously undescribed female-predominant pattern in the heart and white adipose tissue. Crucially, the data demonstrates that Lac-Phe dynamics are governed by upstream substrate availability (lactate) rather than the induction of its synthesizing enzyme, CNDP2. Leveraging this mechanistic insight, a modular computational pipeline was designed to predict clinical viability, validating targets, drug relations, ADMET profiles, and side effects using open data. This pipeline successfully identifies hydrolysis-resistant Lac-Phe isosteres as stable, high-potential exercise mimetics.
Why it matters: By rescuing "invisible" data from the world's largest exercise atlas, this project resolves a core biological paradox of Lac-Phe kinetics. Furthermore, it delivers an end-to-end predictive computational pipeline to de-risk and engineer next-generation exercise mimetics prior to costly wet-lab synthesis.
README excerpt
# Lac-Phe as a Substrate-Driven Exerkine in the MoTrPAC Atlas ### Recovering an "invisible" exercise metabolite from raw spectra, showing its kinetics are substrate- (not enzyme-) driven, and computationally designing hydrolysis-resistant mimetics Reproducibility package — regeneration code, LaTeX source, figures, deposited analysis-ready data, an independent three-track correctness audit, and Claude Science session logs — for: > **Multi-Omic Profiling Reveals Lac-Phe as a Substrate-Driven Exerkine Independent of CNDP2 Activation** > Steven Hershman (Independent Researcher) · Claude Science (Anthropic) **Built with Claude — Life Sciences Hackathon · Researcher Track** 📺 Demo video (≤3 min): https://youtu.be/iSjRvYeJd44 📦 Repository: https://github.com/hershman/claude-science-lacphe-motrpac --- ## TL;DR *N*-lactoyl-phenylalanine (Lac-Phe) is a CNDP2-derived, exercise-inducible metabolite that suppresses feeding and adiposity — yet it appears in **no released MoTrPAC metabolomics feature table**. Returning to the raw mass-spectrometry files, this project recovered a Lac-Phe-mass ion across **all 19 PASS1B rat tissues**, showed the training response is **transient and female-predominant** (statistically robust only in the **heart**, q = 0.014, on the selection-free omnibus), and demonstrated that **CNDP2 is not activated** by training at any regulatory layer — implying Lac-Phe production is **substrate-driven flux** (local lactate + phenylalanine), not enzyme induction. B