Quantitative Comparison of Statistical Methods for Analyzing Human Metabolomics Data

Brian L. Claggett; Joseph Antonelli; Mir Henglin; Jeramie D. Watrous; Kim A. Lehmann; Gabriel Musso; Andrew Correia; Sivani Jonnalagadda; Olga V. Demler; Ramachandran S. Vasan; Martin G. Larson; Mohit Jain; Susan Cheng

arXiv · 1710.03443

Quantitative Comparison of Statistical Methods for Analyzing Human Metabolomics Data

Brian L. Claggett·Joseph Antonelli·Mir Henglin·Jeramie D. Watrous·Kim A. Lehmann·Gabriel Musso·Andrew Correia·Sivani Jonnalagadda·Olga V. Demler·Ramachandran S. Vasan·Martin G. Larson·Mohit Jain·Susan Cheng

View original source ↗Read source document ↗Export metadata ↓

Abstract

Background. Emerging technologies now allow for mass spectrometry based profiling of up to thousands of small molecule metabolites (metabolomics) in an increasing number of biosamples. While offering great promise for revealing insight into the pathogenesis of human disease, standard approaches have yet to be established for statistically analyzing increasingly complex, high-dimensional human metabolomics data in relation to clinical phenotypes including disease outcomes. To determine optimal statistical approaches for metabolomics analysis, we sought to formally compare traditional statistical as well as newer statistical learning methods across a range of metabolomics dataset types. Results. In simulated and experimental metabolomics data derived from large population-based human cohorts, we observed that with an increasing number of study subjects, univariate compared to multivariate methods resulted in a higher false discovery rate due to substantial correlations among metabolites. In scenarios wherein the number of assayed metabolites increases, as in the application of nontargeted versus targeted metabolomics measures, multivariate methods performed especially favorably across a range of statistical operating characteristics. In nontargeted metabolomics datasets that included thousands of metabolite measures, sparse multivariate models demonstrated greater selectivity and lower potential for spurious relationships. Conclusion. When the number of metabolites was similar to or exceeded the number of study subjects, as is common with nontargeted metabolomics analysis of relatively small sized cohorts, sparse multivariate models exhibited the most robust statistical power with more consistent results. These findings have important implications for the analysis of metabolomics studies of human disease.

Explore related subjects

q-bio.QM stat.AP

Keep this discovery

BibTeX RIS

Brian L. Claggett, Joseph Antonelli, Mir Henglin, Jeramie D. Watrous, Kim A. Lehmann, Gabriel Musso, Andrew Correia, Sivani Jonnalagadda, Olga V. Demler, Ramachandran S. Vasan, Martin G. Larson, Mohit Jain, Susan Cheng. 2017-10-10. Quantitative Comparison of Statistical Methods for Analyzing Human Metabolomics Data. https://arxiv.org/abs/1710.03443

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

arXiv2026

Biology-in-the-loop: Amortized Adaptive Hit Discovery in CRISPR Screens

Many biological discovery problems require experiments to be selected sequentially under constrained budgets. CRISPR screening is a prominent example, as exhaustive perturbation testing is often infeasible and candidate perturbations must instead be prioritized over multiple experimental rounds. Despite the importance of this problem, existing benchmarks for adaptive hit discovery remain limited in scale and diversity. Here, we introduce AssayBench-Loop, a large-scale benchmark for adaptive hit discovery comprising 1,389 CRISPR screens across five phenotype categories. Beyond enabling systematic evaluation, its scale makes it possible to learn acquisition strategies across historical experiments. Building on this resource, we introduce AssayLoop, a sequential experimental design framework combining AssayFormer, a transformer-based amortized acquisition policy trained across historical screens to adapt from experimental feedback, with LLM-derived biological priors through an adaptive handoff. In this view, completed experiments become training data for learning how accumulated evidence should guide what to test next, while LLMs provide prior biological knowledge to seed the search. We further introduce AssayLLM, showing that the same principle can be extended directly to an LLM through task-specific post-training. On temporally held-out screens, AssayLoop achieves a 5.67-fold enrichment over random selection and recovers 27.7% of hits after assaying approximately 5% of the candidate library, outperforming existing adaptive-design methods and standalone LLMs, and AssayFormer alone. Performance improves with increasing historical training data and transfers to phenotype categories excluded from training. These results demonstrate the value of learning acquisition policies across historical experiments and combining them with broad biological priors for efficient adaptive hit discovery.

q-bio.QM↗

arXiv2026

Multi-Task Bacterial Colony Detection and Classification Using YOLOv8 with Edge Optimization for Resource-Constrained Deployment

Manual counting and classification of bacterial colonies are critical yet labor-intensive tasks in microbiology, prone to human error particularly on densely populated plates. This work proposes a multi-task deep learning framework trained on the Annotated Germs for Automated Recognition (AGAR) dataset (18,000 images; 9,202 training / 3,067 testing) to automate Colony Forming Unit (CFU) enumeration and species classification. A custom multi-task CNN employing global regression served as the baseline, but demonstrated limited performance in clustered colony environments due to the absence of spatial localization. To address this, a YOLOv8 object detection architecture was adopted with high-resolution 1024x1024 inputs, enabling instance-level colony detection and label assignment. The model achieved a classification accuracy of 98.13% and a counting accuracy of 98.27% (within a 10-colony margin), demonstrating strong predictive capability. To bridge the gap between model performance and practical deployability, the trained model was optimized through unstructured and structured pruning, ONNX conversion, and reduced-precision inference (FP32, FP16, INT8). On a Raspberry Pi 4B, ONNX FP32 and FP16 variants offered the best balance between inference speed (~6.4s) and accuracy (MAE ~2.20). Unstructured pruning preserved predictive accuracy (MAE ~2.01) without runtime gains, while structured pruning resulted in significant accuracy degradation (MAE ~6.3), revealing the sensitivity of instance-level colony detection to architectural compression. These findings provide practical guidance for selecting optimization strategies in resource-constrained laboratory deployments.

q-bio.QM↗

arXiv2026

ADMET-EvO: a self-evolving scientific agent for sustained research across heterogeneous tasks

Scientific agents can move beyond automated model building by using accumulated evidence to revise both their questions and experimental strategies. The challenge is sustaining this adaptation across heterogeneous tasks without overfitting decisions to internal validation. Absorption, distribution, metabolism, excretion and toxicity (ADMET) prediction provides a demanding setting across diverse assays, datasets and chemical domains. We therefore developed ADMET-EvO, an evidence-gated agent that formalizes endpoints, generates falsifiable hypotheses and tests interventions across data, feature and model axes. It carries supported, rejected and inconclusive outcomes forward to guide each new cycle. Across the 22-task Therapeutics Data Commons (TDC) ADMET benchmark, ADMET-EvO achieved the highest task-normalized score of 96.77. Evidence-guided selection reduced cumulative fitting time by 72.2% within a predefined non-inferiority margin. It also formalized 43 toxicity-related tasks and constructed endpoint-specific predictors. Together, these results show how ADMET-EvO can accumulate evidence, revise its strategy and expand its research scope over time.

q-bio.QM↗