# Revealing Interconnections between Diseases: from Statistical Methods to Large Language Models

arXiv: https://arxiv.org/abs/2510.04888 · HTML: https://mlsanity.com/paper/2510.04888/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 13 of its 33 references that are in the map.
- First posted on arXiv 6 Oct 2025.

## Builds on (most cited first, 13 of 13)

- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [Aligning Books and Movies: Towards Story-like Visual Explanations by Watching Movies and Reading Books](https://mlsanity.com/paper/1506.06724/) (2015)
- [ClinicalBERT: Modeling Clinical Notes and Predicting Hospital Readmission](https://mlsanity.com/paper/1904.05342/) (2019)
- [Med-BERT: pre-trained contextualized embeddings on large-scale structured electronic health records for disease prediction](https://mlsanity.com/paper/2005.12833/) (2020)
- [BEHRT: Transformer for Electronic Health Records](https://mlsanity.com/paper/1907.09538/) (2019)
- [Deep EHR: A Survey of Recent Advances in Deep Learning Techniques for Electronic Health Record (EHR) Analysis](https://mlsanity.com/paper/1706.03446/) (2017)
- [Pre-training of Graph Augmented Transformers for Medication Recommendation](https://mlsanity.com/paper/1906.00346/) (2019)
- [AriGraph: Learning Knowledge Graph World Models with Episodic Memory for LLM Agents](https://mlsanity.com/paper/2407.04363/) (2024)
- [CEHR-BERT: Incorporating temporal information from structured EHR data to improve prediction tasks](https://mlsanity.com/paper/2111.08585/) (2021)
- [Large Language Models to Identify Social Determinants of Health in Electronic Health Records](https://mlsanity.com/paper/2308.06354/) (2023)
- [ExBEHRT: Extended Transformer for Electronic Health Records to Predict Disease Subtypes & Progressions](https://mlsanity.com/paper/2303.12364/) (2023)
- [Recent Advances in Predictive Modeling with Electronic Health Records](https://mlsanity.com/paper/2402.01077/) (2024)
- [LLMs-based Few-Shot Disease Predictions using EHR: A Novel Approach Combining Predictive Agent Reasoning and Critical Agent Instruction](https://mlsanity.com/paper/2403.15464/) (2024)

## Abstract (arXiv)

Identifying disease interconnections through manual analysis of large-scale clinical data is labor-intensive, subjective, and prone to expert disagreement. While machine learning (ML) shows promise, three critical challenges remain: (1) selecting optimal methods from the vast ML landscape, (2) determining whether real-world clinical data (e.g., electronic health records, EHRs) or structured disease descriptions yield more reliable insights, (3) the lack of "ground truth," as some disease interconnections remain unexplored in medicine. Large language models (LLMs) demonstrate broad utility, yet they often lack specialized medical knowledge. To address these gaps, we conduct a systematic evaluation of seven approaches for uncovering disease relationships based on two data sources: (i) sequences of ICD-10 codes from MIMIC-IV EHRs and (ii) the full set of ICD-10 codes, both with and without textual descriptions. Our framework integrates the following: (i) a statistical co-occurrence analysis and a masked language modeling (MLM) approach using real clinical data; (ii) domain-specific BERT variants (Med-BERT and BioClinicalBERT); (iii) a general-purpose BERT and document retrieval; and (iv) four LLMs (Mistral, DeepSeek, Qwen, and YandexGPT). Our graph-based comparison of the obtained interconnection matrices shows that the LLM-based approach produces interconnections with the lowest diversity of ICD code connections to different diseases compared to other methods, including text-based and domain-based approaches. This suggests an important implication: LLMs have limited potential for discovering new interconnections. In the absence of ground truth databases for medical interconnections between ICD codes, our results constitute a valuable medical disease ontology that can serve as a foundational resource for future clinical research and artificial intelligence applications in healthcare.