Biomarker discovery is vital in advancing personalized medicine, offering insights into disease diagnosis, prognosis, and therapeutic efficacy. Traditionally, the identification and validation of biomarkers heavily depend on extensive experiments and statistical analyses. These approaches are time-consuming, demand extensive domain expertise, and are constrained by the complexity of biological systems. These limitations motivate us to ask: Can we automatically identify the effective biomarker subset without substantial human efforts? Inspired by the success of generative AI, we think that the intricate knowledge of biomarker identification can be compressed into a continuous embedding space, thus enhancing the search for better biomarkers. Thus, we propose a new biomarker identification framework with two important modules:1) training data preparation and 2) embedding-optimization-generation. The first module uses a multi-agent system to automatically collect pairs of biomarker subsets and their corresponding prediction accuracy as training data. These data establish a strong knowledge base for biomarker identification. The second module employs an encoder-evaluator-decoder learning paradigm to compress the knowledge of the collected data into a continuous space. Then, it utilizes gradient-based search techniques and autoregressive-based reconstruction to efficiently identify the optimal subset of biomarkers. Finally, we conduct extensive experiments on three real-world datasets to show the efficiency, robustness, and effectiveness of our method.

Recent advances in experimental methods have enabled researchers to collect data on thousands of analytes simultaneously. This has led to correlational studies that associated molecular measurements with diseases such as Alzheimer's, Liver, and Gastric Cancer. However, the use of thousands of biomarkers selected from the analytes is not practical for real-world medical diagnosis and is likely undesirable due to potentially formed spurious correlations. In this study, we evaluate 4 different methods for biomarker selection and 4 different machine learning (ML) classifiers for identifying correlations - evaluating 16 approaches in all. We found that contemporary methods outperform previously reported logistic regression in cases where 3 and 10 biomarkers are permitted. When specificity is fixed at 0.9, ML approaches produced a sensitivity of 0.240 (3 biomarkers) and 0.520 (10 biomarkers), while standard logistic regression provided a sensitivity of 0.000 (3 biomarkers) and 0.040 (10 biomarkers). We also noted that causal-based methods for biomarker selection proved to be the most performant when fewer biomarkers were permitted, while univariate feature selection was the most performant when a greater number of biomarkers were permitted.