Search arXiv⌕ Search
Home/Archive/arXiv

arXiv · 2505.02514

Uncovering Population PK Covariates from VAE-Generated Latent Spaces

Diego Perazzolo·Chiara Castellani·Enrico Grisan
View original source ↗Read source document ↗Export metadata ↓

Abstract

Population pharmacokinetic (PopPK) modelling is a fundamental tool for understanding drug behaviour across diverse patient populations and enabling personalized dosing strategies to improve therapeutic outcomes. A key challenge in PopPK analysis lies in identifying and modelling covariates that influence drug absorption, as these relationships are often complex and nonlinear. Traditional methods may fail to capture hidden patterns within the data. In this study, we propose a data-driven, model-free framework that integrates Variational Autoencoders (VAEs) deep learning model and LASSO regression to uncover key covariates from simulated tacrolimus pharmacokinetic (PK) profiles. The VAE compresses high-dimensional PK signals into a structured latent space, achieving accurate reconstruction with a mean absolute percentage error (MAPE) of 2.26%. LASSO regression is then applied to map patient-specific covariates to the latent space, enabling sparse feature selection through L1 regularization. This approach consistently identifies clinically relevant covariates for tacrolimus including SNP, age, albumin, and hemoglobin which are retained across the tested regularization strength levels, while effectively discarding non-informative features. The proposed VAE-LASSO methodology offers a scalable, interpretable, and fully data-driven solution for covariate selection, with promising applications in drug development and precision pharmacotherapy.

Explore related subjects

cs.LGq-bio.QM

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Diego Perazzolo, Chiara Castellani, Enrico Grisan. 2025-05-05. Uncovering Population PK Covariates from VAE-Generated Latent Spaces. https://arxiv.org/abs/2505.02514

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

KEEP EXPLORING

Related papers

arXiv2026

A Probabilistic Approach for Model Alignment with Human Comparisons

A growing trend involves integrating human knowledge into learning frameworks, leveraging subtle human feedback to refine AI models. While these approaches have shown promising results in practice, the theoretical understanding of when and why such approaches are effective remains limited. This work takes steps toward developing a theoretical framework for analyzing the conditions under which human comparisons can enhance the traditional supervised learning process. Specifically, this paper studies the effective use of noisy-labeled data and human comparison data to address challenges arising from noisy environment and high-dimensional models. We propose a two-stage "Supervised Learning+Learning from Human Feedback" (SL+LHF) framework that connects machine learning with human feedback through a probabilistic bisection approach. The two-stage framework first learns low-dimensional representations from noisy-labeled data via an SL procedure and then uses human comparisons to improve the model alignment. To examine the efficacy of the alignment phase, we introduce a concept, termed the "label-noise-to-comparison-accuracy" (LNCA) ratio. This paper identifies from a theoretical perspective the conditions under which the "SL+LHF" framework outperforms the pure SL approach; we then leverage this LNCA ratio to highlight the advantage of incorporating human evaluators in reducing sample complexity. We validate the framework on a real high-dimensional crowdfunding-prediction task: under a fixed query budget, trading labels for comparisons improves accuracy precisely when labels are scarce, and the findings hold when the evaluator is replaced by real large language models. A study conducted via Amazon Mechanical Turk (MTurk) further validates the model primitives.

cs.LG↗
arXiv2026

An Initial Introduction to Cooperative Multi-Agent Reinforcement Learning

Multi-agent reinforcement learning (MARL) has exploded in popularity in recent years. While numerous approaches have been developed, they can be broadly categorized into three main types: centralized training and execution (CTE), centralized training for decentralized execution (CTDE), and decentralized training and execution (DTE). CTE methods assume centralization during training and execution (e.g., with fast, free, and perfect communication) and have the most information during execution. CTDE methods are the most common, as they leverage centralized information during training while enabling decentralized execution -- using only information available to that agent during execution. Decentralized training and execution methods make the fewest assumptions and are often simple to implement. This text is an introduction to cooperative MARL -- MARL in which all agents share a single, joint reward. It is meant to explain the setting, basic concepts, and common methods for the CTE, CTDE, and DTE settings. It does not cover all work in cooperative MARL as the area is quite extensive. I have included work that I believe is important for understanding the main concepts in the area and apologize to those that I have omitted. Topics include simple applications of single-agent methods to CTE as well as some more scalable methods that exploit the multi-agent structure, independent Q-learning and policy gradient methods and their extensions, as well as value function factorization methods including the well-known VDN, QMIX, and QPLEX approaches, and centralized critic methods including MADDPG, COMA, and MAPPO. I also discuss common misconceptions, the relationship between different approaches, and some open questions.

cs.LG↗
arXiv2026

TIDE: Temporal Incremental Draft Engine for Self-Improving LLM Inference

Speculative decoding can substantially accelerate LLM inference, but realizing its benefits in practice is challenging due to evolving workloads. We present TIDE (Temporal Incremental Draft Engine), a serving-engine-native framework that integrates online draft adaptation directly into high-performance LLM inference systems. TIDE reuses target model's intermediate hidden states generated during inference as training signals for draft adaptation, thereby avoiding additional target model computation and serving-time overhead. It employs adaptive runtime control to activate speculation and draft model training only when beneficial. TIDE exploits heterogeneous clusters by mapping inference and training to appropriate GPU classes. Across diverse real-world workloads, TIDE achieves up to 1.66$\times$ throughput over no-speculation baselines while recovering performance on misaligned workloads where static draft models degrade throughput. TIDE also reduces training time by up to 3.02$\times$ and storage requirements by 24$\times$ compared to existing draft training approaches, and improves system throughput by up to 1.22$\times$ on heterogeneous GPU clusters.

cs.LG↗