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In tabular biomedical data analysis, tuning models to high accuracy is considered a prerequisite for discussing feature importance, as medical practitioners expect the validity of feature importance to correlate with performance. In this work, we challenge the prevailing belief, showing that low-performing models may also be used for feature importance. We propose experiments to observe changes in feature rank as performance degrades sequentially. Using three synthetic datasets and six real biomedical datasets, we compare the rank of features from full datasets to those with reduced sample sizes (data cutting) or fewer features (feature cutting). In synthetic datasets, feature cutting does not change feature rank, while data cutting shows higher discrepancies with lower performance. In real datasets, feature cutting shows similar or smaller changes than data cutting, though some datasets exhibit the opposite. When feature interactions are controlled by removing correlations, feature cutting consistently shows better stability. By analyzing the distribution of feature importance values and theoretically examining the probability that the model cannot distinguish feature importance between features, we reveal that models can still distinguish feature importance despite performance degradation through feature cutting, but not through data cutting. We conclude that the validity of feature importance can be maintained even at low performance levels if the data size is adequate, which is a significant factor contributing to suboptimal performance in tabular medical data analysis. This paper demonstrates the potential for utilizing feature importance analysis alongside statistical analysis to compare features relatively, even when classifier performance is not satisfactory.

Many data sets cannot be accurately described by standard probability distributions due to the excess number of zero values present. For example, zero-inflation is prevalent in microbiome data and single-cell RNA sequencing data, which serve as our real data examples. Several models have been proposed to address zero-inflated datasets including the zero-inflated negative binomial, hurdle negative binomial model, and the truncated latent Gaussian copula model. This study aims to compare various models and determine which one performs optimally under different conditions using both simulation studies and real data analyses. We are particularly interested in investigating how dependence among the variables, level of zero-inflation or deflation, and variance of the data affects model selection.

We present BALDUR, a novel Bayesian algorithm designed to deal with multi-modal datasets and small sample sizes in high-dimensional settings while providing explainable solutions. To do so, the proposed model combines within a common latent space the different data views to extract the relevant information to solve the classification task and prune out the irrelevant/redundant features/data views. Furthermore, to provide generalizable solutions in small sample size scenarios, BALDUR efficiently integrates dual kernels over the views with a small sample-to-feature ratio. Finally, its linear nature ensures the explainability of the model outcomes, allowing its use for biomarker identification. This model was tested over two different neurodegeneration datasets, outperforming the state-of-the-art models and detecting features aligned with markers already described in the scientific literature., Comment: 36 pages, 3 figures and 3 tables

Biomedical research requires large, diverse samples to produce unbiased results. Automated methods for matching variables across datasets can accelerate this process. Research in this area has been limited, primarily focusing on lexical matching and ontology based semantic matching. We aimed to develop new methods, leveraging large language models (LLM) and ensemble learning, to automate variable matching. Methods: We utilized data from two GERAS cohort (European and Japan) studies to develop variable matching methods. We first manually created a dataset by matching 352 EU variables with 1322 candidate JP variables, where matched variable pairs were positive and unmatched pairs were negative instances. Using this dataset, we developed and evaluated two types of natural language processing (NLP) methods, which matched variables based on variable labels and definitions from data dictionaries: (1) LLM-based and (2) fuzzy matching. We then developed an ensemble-learning method, using the Random Forest model, to integrate individual NLP methods. RF was trained and evaluated on 50 trials. Each trial had a random split (4:1) of training and test sets, with the model's hyperparameters optimized through cross-validation on the training set. For each EU variable, 1322 candidate JP variables were ranked based on NLP-derived similarity scores or RF's probability scores, denoting their likelihood to match the EU variable. Ranking performance was measured by top-n hit ratio (HRn) and mean reciprocal rank (MRR). Results:E5 performed best among individual methods, achieving 0.90 HR-30 and 0.70 MRR. RF performed better than E5 on all metrics over 50 trials (P less than 0.001) and achieved an average HR 30 of 0.98 and MRR of 0.73. LLM-derived features contributed most to RF's performance. One major cause of errors in automatic variable matching was ambiguous variable definitions within data dictionaries., Comment: 32 pages, 2 figures

In contemporary biomedical research, the efficiency of data-driven approaches is hindered by large data volumes, tool selection complexity, and human resource limitations, necessitating the development of fully autonomous research systems to meet complex analytical needs. Such a system should include the ability to autonomously generate research questions, write analytical code, configure the computational environment, judge and interpret the results, and iteratively generate in-depth questions or solutions, all without human intervention. Here we developed DREAM, the first biomedical Data-dRiven self-Evolving Autonomous systeM, which can independently conduct scientific research without human involvement. Utilizing a clinical dataset and two omics datasets, DREAM demonstrated its ability to raise and deepen scientific questions, with difficulty scores for clinical data questions surpassing top published articles by 5.7% and outperforming GPT-4 and bioinformatics graduate students by 58.6% and 56.0%, respectively. Overall, DREAM has a success rate of 80% in autonomous clinical data mining. Certainly, human can participate in different steps of DREAM to achieve more personalized goals. After evolution, 10% of the questions exceeded the average scores of top published article questions on originality and complexity. In the autonomous environment configuration of the eight bioinformatics workflows, DREAM exhibited an 88% success rate, whereas GPT-4 failed to configure any workflows. In clinical dataset, DREAM was over 10,000 times more efficient than the average scientist with a single computer core, and capable of revealing new discoveries. As a self-evolving autonomous research system, DREAM provides an efficient and reliable solution for future biomedical research. This paradigm may also have a revolutionary impact on other data-driven scientific research fields., Comment: 11 pages, 4 figures, content added, typos in figure corrected, references revised and font changed

Clinical and biomedical research in low-resource settings often faces significant challenges due to the need for high-quality data with sufficient sample sizes to construct effective models. These constraints hinder robust model training and prompt researchers to seek methods for leveraging existing knowledge from related studies to support new research efforts. Transfer learning (TL), a machine learning technique, emerges as a powerful solution by utilizing knowledge from pre-trained models to enhance the performance of new models, offering promise across various healthcare domains. Despite its conceptual origins in the 1990s, the application of TL in medical research has remained limited, especially beyond image analysis. In our review of TL applications in structured clinical and biomedical data, we screened 3,515 papers, with 55 meeting the inclusion criteria. Among these, only 2% (one out of 55) utilized external studies, and 7% (four out of 55) addressed scenarios involving multi-site collaborations with privacy constraints. To achieve actionable TL with structured medical data while addressing regional disparities, inequality, and privacy constraints in healthcare research, we advocate for the careful identification of appropriate source data and models, the selection of suitable TL frameworks, and the validation of TL models with proper baselines.

Effective clustering of biomedical data is crucial in precision medicine, enabling accurate stratifiction of patients or samples. However, the growth in availability of high-dimensional categorical data, including `omics data, necessitates computationally efficient clustering algorithms. We present VICatMix, a variational Bayesian finite mixture model designed for the clustering of categorical data. The use of variational inference (VI) in its training allows the model to outperform competitors in term of efficiency, while maintaining high accuracy. VICatMix furthermore performs variable selection, enhancing its performance on high-dimensional, noisy data. The proposed model incorporates summarisation and model averaging to mitigate poor local optima in VI, allowing for improved estimation of the true number of clusters simultaneously with feature saliency. We demonstrate the performance of VICatMix with both simulated and real-world data, including applications to datasets from The Cancer Genome Atlas (TCGA), showing its use in cancer subtyping and driver gene discovery. We demonstrate VICatMix's utility in integrative cluster analysis with different `omics datasets, enabling the discovery of novel subtypes. \textbf{Availability:} VICatMix is freely available as an R package, incorporating C++ for faster computation, at \url{https://github.com/j-ackierao/VICatMix}.

This paper presents the development of a prototype Automatic Speech Recognition (ASR) system specifically designed for Bengali biomedical data. Recent advancements in Bengali ASR are encouraging, but a lack of domain-specific data limits the creation of practical healthcare ASR models. This project bridges this gap by developing an ASR system tailored for Bengali medical terms like symptoms, severity levels, and diseases, encompassing two major dialects: Bengali and Sylheti. We train and evaluate two popular ASR frameworks on a comprehensive 46-hour Bengali medical corpus. Our core objective is to create deployable health-domain ASR systems for digital health applications, ultimately increasing accessibility for non-technical users in the healthcare sector.

Deep learning based approaches are now widely used across biophysics to help automate a variety of tasks including image segmentation, feature selection, and deconvolution. However, the presence of multiple competing deep learning architectures, each with its own unique advantages and disadvantages, makes it challenging to select an architecture best suited for a specific application. As such, we present a comprehensive comparison of common models. Here, we focus on the task of segmentation assuming the typically small training dataset sizes available from biophysics experiments and compare the following four commonly used architectures: convolutional neural networks, U-Nets, vision transformers, and vision state space models. In doing so, we establish criteria for determining optimal conditions under which each model excels, thereby offering practical guidelines for researchers and practitioners in the field.

This paper introduces the DeepATLAS foundational model for localization tasks in the domain of high-dimensional biomedical data. Upon convergence of the proposed self-supervised objective, a pretrained model maps an input to an anatomically-consistent embedding from which any point or set of points (e.g., boxes or segmentations) may be identified in a one-shot or few-shot approach. As a representative benchmark, a DeepATLAS model pretrained on a comprehensive cohort of 51,000+ unlabeled 3D computed tomography exams yields high one-shot segmentation performance on over 50 anatomic structures across four different external test sets, either matching or exceeding the performance of a standard supervised learning model. Further improvements in accuracy can be achieved by adding a small amount of labeled data using either a semisupervised or more conventional fine-tuning strategy., Comment: 18 pages

The increasing requirements for data protection and privacy has attracted a huge research interest on distributed artificial intelligence and specifically on federated learning, an emerging machine learning approach that allows the construction of a model between several participants who hold their own private data. In the initial proposal of federated learning the architecture was centralised and the aggregation was done with federated averaging, meaning that a central server will orchestrate the federation using the most straightforward averaging strategy. This research is focused on testing different federated strategies in a peer-to-peer environment. The authors propose various aggregation strategies for federated learning, including weighted averaging aggregation, using different factors and strategies based on participant contribution. The strategies are tested with varying data sizes to identify the most robust ones. This research tests the strategies with several biomedical datasets and the results of the experiments show that the accuracy-based weighted average outperforms the classical federated averaging method.

Accurately labeling biomedical data presents a challenge. Traditional semi-supervised learning methods often under-utilize available unlabeled data. To address this, we propose a novel reliability-based training data cleaning method employing inductive conformal prediction (ICP). This method capitalizes on a small set of accurately labeled training data and leverages ICP-calculated reliability metrics to rectify mislabeled data and outliers within vast quantities of noisy training data. The efficacy of the method is validated across three classification tasks within distinct modalities: filtering drug-induced-liver-injury (DILI) literature with title and abstract, predicting ICU admission of COVID-19 patients through CT radiomics and electronic health records, and subtyping breast cancer using RNA-sequencing data. Varying levels of noise to the training labels were introduced through label permutation. Results show significant enhancements in classification performance: accuracy enhancement in 86 out of 96 DILI experiments (up to 11.4%), AUROC and AUPRC enhancements in all 48 COVID-19 experiments (up to 23.8% and 69.8%), and accuracy and macro-average F1 score improvements in 47 out of 48 RNA-sequencing experiments (up to 74.6% and 89.0%). Our method offers the potential to substantially boost classification performance in multi-modal biomedical machine learning tasks. Importantly, it accomplishes this without necessitating an excessive volume of meticulously curated training data.

Technological advances in medical data collection, such as high-throughput genomic sequencing and digital high-resolution histopathology, have contributed to the rising requirement for multimodal biomedical modelling, specifically for image, tabular and graph data. Most multimodal deep learning approaches use modality-specific architectures that are often trained separately and cannot capture the crucial cross-modal information that motivates the integration of different data sources. This paper presents the Hybrid Early-fusion Attention Learning Network (HEALNet): a flexible multimodal fusion architecture, which a) preserves modality-specific structural information, b) captures the cross-modal interactions and structural information in a shared latent space, c) can effectively handle missing modalities during training and inference, and d) enables intuitive model inspection by learning on the raw data input instead of opaque embeddings. We conduct multimodal survival analysis on Whole Slide Images and Multi-omic data on four cancer datasets from The Cancer Genome Atlas (TCGA). HEALNet achieves state-of-the-art performance compared to other end-to-end trained fusion models, substantially improving over unimodal and multimodal baselines whilst being robust in scenarios with missing modalities., Comment: NeurIPS 2024

Background: Biomedical data are usually collections of longitudinal data assessed at certain points in time. Clinical observations assess the presences and severity of symptoms, which are the basis for description and modeling of disease progression. Deciphering potential underlying unknowns solely from the distinct observation would substantially improve the understanding of pathological cascades. Hidden Markov Models (HMMs) have been successfully applied to the processing of possibly noisy continuous signals. The aim was to improve the application HMMs to multivariate time-series of categorically distributed data. Here, we used HHMs to study prediction of the loss of free walking ability as one major clinical deterioration in the most common autosomal dominantly inherited ataxia disorder worldwide. We used HHMs to investigate the prediction of loss of the ability to walk freely, representing a major clinical deterioration in the most common autosomal-dominant inherited ataxia disorder worldwide. Results: We present a prediction pipeline which processes data paired with a configuration file, enabling to construct, validate and query a fully parameterized HMM-based model. In particular, we provide a theoretical and practical framework for multivariate time-series inference based on HMMs that includes constructing multiple HMMs, each to predict a particular observable variable. Our analysis is done on random data, but also on biomedical data based on Spinocerebellar ataxia type 3 disease. Conclusions: HHMs are a promising approach to study biomedical data that naturally are represented as multivariate time-series. Our implementation of a HHMs framework is publicly available and can easily be adapted for further applications.

Clinical data in hospitals are increasingly accessible for research through clinical data warehouses. However these documents are unstructured and it is therefore necessary to extract information from medical reports to conduct clinical studies. Transfer learning with BERT-like models such as CamemBERT has allowed major advances for French, especially for named entity recognition. However, these models are trained for plain language and are less efficient on biomedical data. Addressing this gap, we introduce CamemBERT-bio, a dedicated French biomedical model derived from a new public French biomedical dataset. Through continual pre-training of the original CamemBERT, CamemBERT-bio achieves an improvement of 2.54 points of F1-score on average across various biomedical named entity recognition tasks, reinforcing the potential of continual pre-training as an equally proficient yet less computationally intensive alternative to training from scratch. Additionally, we highlight the importance of using a standard evaluation protocol that provides a clear view of the current state-of-the-art for French biomedical models., Comment: Accepted to LREC-COLING 2024

Tabular biomedical data poses challenges in machine learning because it is often high-dimensional and typically low-sample-size (HDLSS). Previous research has attempted to address these challenges via local feature selection, but existing approaches often fail to achieve optimal performance due to their limitation in identifying globally important features and their susceptibility to the co-adaptation problem. In this paper, we propose ProtoGate, a prototype-based neural model for feature selection on HDLSS data. ProtoGate first selects instance-wise features via adaptively balancing global and local feature selection. Furthermore, ProtoGate employs a non-parametric prototype-based prediction mechanism to tackle the co-adaptation problem, ensuring the feature selection results and predictions are consistent with underlying data clusters. We conduct comprehensive experiments to evaluate the performance and interpretability of ProtoGate on synthetic and real-world datasets. The results show that ProtoGate generally outperforms state-of-the-art methods in prediction accuracy by a clear margin while providing high-fidelity feature selection and explainable predictions. Code is available at https://github.com/SilenceX12138/ProtoGate., Comment: Accepted by the Forty-first International Conference on Machine Learning (ICML2024)

Multimodal learning models have become increasingly important as they surpass single-modality approaches on diverse tasks ranging from question-answering to autonomous driving. Despite the importance of multimodal learning, existing efforts focus on NLP applications, where the number of modalities is typically less than four (audio, video, text, images). However, data inputs in other domains, such as the medical field, may include X-rays, PET scans, MRIs, genetic screening, clinical notes, and more, creating a need for both efficient and accurate information fusion. Many state-of-the-art models rely on pairwise cross-modal attention, which does not scale well for applications with more than three modalities. For $n$ modalities, computing attention will result in $n \choose 2$ operations, potentially requiring considerable amounts of computational resources. To address this, we propose a new domain-neutral attention mechanism, One-Versus-Others (OvO) attention, that scales linearly with the number of modalities and requires only $n$ attention operations, thus offering a significant reduction in computational complexity compared to existing cross-modal attention algorithms. Using three diverse real-world datasets as well as an additional simulation experiment, we show that our method improves performance compared to popular fusion techniques while decreasing computation costs.

Academic medical centers are generating an increasing amount of biomedical data and there is an increasing demand for biomedical data for research purposes by research projects, research consortia, companies, and other third parties. At the same time, as the number of patients grows and the amount of data per patient grows, there is an increasing possibility that some information about some patients may become available if the data is shared with third parties and the third parties have a data breach or violate the terms of the data use agreement. Balancing the importance of research that may result in improved patient outcomes with the importance of protecting patient data is challenging. The article discusses the principles, considerations about risks and mitigating risks, and guidelines used at the University of Chicago used for making decisions about sharing biomedical data with third parties., Comment: 6 pages

Estimating a covariance matrix is central to high-dimensional data analysis. Empirical analyses of high-dimensional biomedical data, including genomics, proteomics, microbiome, and neuroimaging, among others, consistently reveal strong modularity in the dependence patterns. In these analyses, intercorrelated high-dimensional biomedical features often form communities or modules that can be interconnected with others. While the interconnected community structure has been extensively studied in biomedical research (e.g., gene co-expression networks), its potential to assist in the estimation of covariance matrices remains largely unexplored. To address this gap, we propose a procedure that leverages the commonly observed interconnected community structure in high-dimensional biomedical data to estimate large covariance and precision matrices. We derive the uniformly minimum-variance unbiased estimators for covariance and precision matrices in closed forms and provide theoretical results on their asymptotic properties. Our proposed method enhances the accuracy of covariance- and precision-matrix estimation and demonstrates superior performance compared to the competing methods in both simulations and real data analyses.