Can Large Language Models Replace Data Scientists in Clinical Research?

Data science plays a critical role in clinical research, but it requires professionals with expertise in coding and medical data analysis. Large language models (LLMs) have shown great potential in supporting medical tasks and performing well in general coding tests. However, these tests do not assess LLMs' ability to handle data science tasks in medicine, nor do they explore their practical utility in clinical research. To address this, we developed a dataset consisting of 293 real-world data science coding tasks, based on 39 published clinical studies, covering 128 tasks in Python and 165 tasks in R. This dataset simulates realistic clinical research scenarios using patient data. Our findings reveal that cutting-edge LLMs struggle to generate perfect solutions, frequently failing to follow input instructions, understand target data, and adhere to standard analysis practices. Consequently, LLMs are not yet ready to fully automate data science tasks. We benchmarked advanced adaptation methods and found two to be particularly effective: chain-of-thought prompting, which provides a step-by-step plan for data analysis, which led to a 60% improvement in code accuracy; and self-reflection, enabling LLMs to iteratively refine their code, yielding a 38% accuracy improvement. Building on these insights, we developed a platform that integrates LLMs into the data science workflow for medical professionals. In a user study with five medical doctors, we found that while LLMs cannot fully automate coding tasks, they significantly streamline the programming process. We found that 80% of their submitted code solutions were incorporated from LLM-generated code, with up to 96% reuse in some cases. Our analysis highlights the potential of LLMs, when integrated into expert workflows, to enhance data science efficiency in clinical research.

GeSubNet: Gene Interaction Inference for Disease Subtype Network Generation

Retrieving gene functional networks from knowledge databases presents a challenge due to the mismatch between disease networks and subtype-specific variations. Current solutions, including statistical and deep learning methods, often fail to effectively integrate gene interaction knowledge from databases or explicitly learn subtype-specific interactions. To address this mismatch, we propose GeSubNet, which learns a unified representation capable of predicting gene interactions while distinguishing between different disease subtypes. Graphs generated by such representations can be considered subtype-specific networks. GeSubNet is a multi-step representation learning framework with three modules: First, a deep generative model learns distinct disease subtypes from patient gene expression profiles. Second, a graph neural network captures representations of prior gene networks from knowledge databases, ensuring accurate physical gene interactions. Finally, we integrate these two representations using an inference loss that leverages graph generation capabilities, conditioned on the patient separation loss, to refine subtype-specific information in the learned representation. GeSubNet consistently outperforms traditional methods, with average improvements of 30.6%, 21.0%, 20.1%, and 56.6% across four graph evaluation metrics, averaged over four cancer datasets. Particularly, we conduct a biological simulation experiment to assess how the behavior of selected genes from over 11,000 candidates affects subtypes or patient distributions. The results show that the generated network has the potential to identify subtype-specific genes with an 83% likelihood of impacting patient distribution shifts. The GeSubNet resource is available: https://anonymous.4open.science/r/GeSubNet/

CMOB: Large-Scale Cancer Multi-Omics Benchmark with Open Datasets, Tasks, and Baselines

Machine learning has shown great potential in the field of cancer multi-omics studies, offering incredible opportunities for advancing precision medicine. However, the challenges associated with dataset curation and task formulation pose significant hurdles, especially for researchers lacking a biomedical background. Here, we introduce the CMOB, the first large-scale cancer multi-omics benchmark integrates the TCGA platform, making data resources accessible and usable for machine learning researchers without significant preparation and expertise.To date, CMOB includes a collection of 20 cancer multi-omics datasets covering 32 cancers, accompanied by a systematic data processing pipeline. CMOB provides well-processed dataset versions to support 20 meaningful tasks in four studies, with a collection of benchmarks. We also integrate CMOB with two complementary resources and various biological tools to explore broader research avenues.All resources are open-accessible with user-friendly and compatible integration scripts that enable non-experts to easily incorporate this complementary information for various tasks. We conduct extensive experiments on selected datasets to offer recommendations on suitable machine learning baselines for specific applications. Through CMOB, we aim to facilitate algorithmic advances and hasten the development, validation, and clinical translation of machine-learning models for personalized cancer treatments. CMOB is available on GitHub (\url{https://github.com/chenzRG/Cancer-Multi-Omics-Benchmark}).

A Bounding Box is Worth One Token: Interleaving Layout and Text in a Large Language Model for Document Understanding

Recently, many studies have demonstrated that exclusively incorporating OCR-derived text and spatial layouts with large language models (LLMs) can be highly effective for document understanding tasks. However, existing methods that integrate spatial layouts with text have limitations, such as producing overly long text sequences or failing to fully leverage the autoregressive traits of LLMs. In this work, we introduce Interleaving Layout and Text in a Large Language Model (LayTextLLM)} for document understanding. In particular, LayTextLLM projects each bounding box to a single embedding and interleaves it with text, efficiently avoiding long sequence issues while leveraging autoregressive traits of LLMs. LayTextLLM not only streamlines the interaction of layout and textual data but also shows enhanced performance in Key Information Extraction (KIE) and Visual Question Answering (VQA). Comprehensive benchmark evaluations reveal significant improvements, with a 27.0% increase on KIE tasks and 24.1% on VQA tasks compared to previous state-of-the-art document understanding MLLMs, as well as a 15.5% improvement over other SOTA OCR-based LLMs on KIE tasks.

PaDeLLM-NER: Parallel Decoding in Large Language Models for Named Entity Recognition

In this study, we aim to reduce generation latency for Named Entity Recognition (NER) with Large Language Models (LLMs). The main cause of high latency in LLMs is the sequential decoding process, which autoregressively generates all labels and mentions for NER, significantly increase the sequence length. To this end, we introduce Parallel Decoding in LLM for NE} (PaDeLLM-NER), a approach that integrates seamlessly into existing generative model frameworks without necessitating additional modules or architectural modifications. PaDeLLM-NER allows for the simultaneous decoding of all mentions, thereby reducing generation latency. Experiments reveal that PaDeLLM-NER significantly increases inference speed that is 1.76 to 10.22 times faster than the autoregressive approach for both English and Chinese. Simultaneously it maintains the quality of predictions as evidenced by the performance that is on par with the state-of-the-art across various datasets.

Bridging Cross-task Protocol Inconsistency for Distillation in Dense Object Detection

Knowledge distillation (KD) has shown potential for learning compact models in dense object detection. However, the commonly used softmax-based distillation ignores the absolute classification scores for individual categories. Thus, the optimum of the distillation loss does not necessarily lead to the optimal student classification scores for dense object detectors. This cross-task protocol inconsistency is critical, especially for dense object detectors, since the foreground categories are extremely imbalanced. To address the issue of protocol differences between distillation and classification, we propose a novel distillation method with cross-task consistent protocols, tailored for the dense object detection. For classification distillation, we address the cross-task protocol inconsistency problem by formulating the classification logit maps in both teacher and student models as multiple binary-classification maps and applying a binary-classification distillation loss to each map. For localization distillation, we design an IoU-based Localization Distillation Loss that is free from specific network structures and can be compared with existing localization distillation losses. Our proposed method is simple but effective, and experimental results demonstrate its superiority over existing methods. Code is available at https://github.com/TinyTigerPan/BCKD.

MoCLIM: Towards Accurate Cancer Subtyping via Multi-Omics Contrastive Learning with Omics-Inference Modeling

Precision medicine fundamentally aims to establish causality between dysregulated biochemical mechanisms and cancer subtypes. Omics-based cancer subtyping has emerged as a revolutionary approach, as different level of omics records the biochemical products of multistep processes in cancers. This paper focuses on fully exploiting the potential of multi-omics data to improve cancer subtyping outcomes, and hence developed MoCLIM, a representation learning framework. MoCLIM independently extracts the informative features from distinct omics modalities. Using a unified representation informed by contrastive learning of different omics modalities, we can well-cluster the subtypes, given cancer, into a lower latent space. This contrast can be interpreted as a projection of inter-omics inference observed in biological networks. Experimental results on six cancer datasets demonstrate that our approach significantly improves data fit and subtyping performance in fewer high-dimensional cancer instances. Moreover, our framework incorporates various medical evaluations as the final component, providing high interpretability in medical analysis.

Understanding and Unifying Fourteen Attribution Methods with Taylor Interactions

Various attribution methods have been developed to explain deep neural networks (DNNs) by inferring the attribution/importance/contribution score of each input variable to the final output. However, existing attribution methods are often built upon different heuristics. There remains a lack of a unified theoretical understanding of why these methods are effective and how they are related. To this end, for the first time, we formulate core mechanisms of fourteen attribution methods, which were designed on different heuristics, into the same mathematical system, i.e., the system of Taylor interactions. Specifically, we prove that attribution scores estimated by fourteen attribution methods can all be reformulated as the weighted sum of two types of effects, i.e., independent effects of each individual input variable and interaction effects between input variables. The essential difference among the fourteen attribution methods mainly lies in the weights of allocating different effects. Based on the above findings, we propose three principles for a fair allocation of effects to evaluate the faithfulness of the fourteen attribution methods.

Cancer Subtyping by Improved Transcriptomic Features Using Vector Quantized Variational Autoencoder

Defining and separating cancer subtypes is essential for facilitating personalized therapy modality and prognosis of patients. The definition of subtypes has been constantly recalibrated as a result of our deepened understanding. During this recalibration, researchers often rely on clustering of cancer data to provide an intuitive visual reference that could reveal the intrinsic characteristics of subtypes. The data being clustered are often omics data such as transcriptomics that have strong correlations to the underlying biological mechanism. However, while existing studies have shown promising results, they suffer from issues associated with omics data: sample scarcity and high dimensionality. As such, existing methods often impose unrealistic assumptions to extract useful features from the data while avoiding overfitting to spurious correlations. In this paper, we propose to leverage a recent strong generative model, Vector Quantized Variational AutoEncoder (VQ-VAE), to tackle the data issues and extract informative latent features that are crucial to the quality of subsequent clustering by retaining only information relevant to reconstructing the input. VQ-VAE does not impose strict assumptions and hence its latent features are better representations of the input, capable of yielding superior clustering performance with any mainstream clustering method. Extensive experiments and medical analysis on multiple datasets comprising 10 distinct cancers demonstrate the VQ-VAE clustering results can significantly and robustly improve prognosis over prevalent subtyping systems.

Automated Cancer Subtyping via Vector Quantization Mutual Information Maximization

Cancer subtyping is crucial for understanding the nature of tumors and providing suitable therapy. However, existing labelling methods are medically controversial, and have driven the process of subtyping away from teaching signals. Moreover, cancer genetic expression profiles are high-dimensional, scarce, and have complicated dependence, thereby posing a serious challenge to existing subtyping models for outputting sensible clustering. In this study, we propose a novel clustering method for exploiting genetic expression profiles and distinguishing subtypes in an unsupervised manner. The proposed method adaptively learns categorical correspondence from latent representations of expression profiles to the subtypes output by the model. By maximizing the problem -- agnostic mutual information between input expression profiles and output subtypes, our method can automatically decide a suitable number of subtypes. Through experiments, we demonstrate that our proposed method can refine existing controversial labels, and, by further medical analysis, this refinement is proven to have a high correlation with cancer survival rates.