Michael Danziger

Michal Rosen-Zvi, Yoav Kan-Tor, Michael Danziger et al.

Healthcare disparities persist across socioeconomic boundaries, often attributed to unequal access to screening, diagnostics, and therapeutics. However, this perspective highlights that critical biases can emerge much earlier, during data collection and research prioritization, long before clinical implementation in cases where the focus of the studies and the data that is collected is at the molecular level. A vast number of studies focus on collecting omics data but the demographic information associated with these datasets is often not reported in the studies, and when it is reported, it shows big biases. An automated analysis of 4719 PubMed-indexed omics publications from 2015 to 2024 reveals that only a small fraction report ancestry or ethnicity information, with ancestry reporting improving slightly. Analysis of large-scale datasets commonly used for model training, such as CellxGene and GEO, reveals substantial population bias where European-ancestry data dominates. As biomedical foundation models become central to biomedical discovery with a paradigm in which base models are pretrained on large datasets and reusing them time and again for many different downstream tasks, they risk perpetuating or amplifying these early-stage biases, leading to cascading inequities that regulatory interventions cannot fully reverse. We propose a community-wide focus on three foundational principles: Provenance, Openness, and Evaluation Transparency to improve equity and robustness in biomedical AI. This approach aims to foster biomedical innovation that more effectively serves underserved populations and improves health outcomes.

Hongyang Li, Sanjoy Dey, Bum Chul Kwon et al.

Large language models (LLMs) trained on text demonstrated remarkable results on natural language processing (NLP) tasks. These models have been adapted to decipher the language of DNA, where sequences of nucleotides act as "words" that encode genomic functions. However, the genome differs fundamentally from natural language, as it lacks clearly defined words or a consistent grammar. Although DNA language models (DNALMs) such as DNABERT, GENA-LM have achieved high level of performance on genome-related biological tasks, these models do not encode biological functions in the presence of sequence variations. To address this problem, we pre-train foundation models that effectively integrate sequence variations, in particular Single Nucleotide Polymorphisms (SNPs), as they underlie important biological functions. Specifically, we use ModernBERT to pre-train two different Biomedical Foundation Models (BMFM), namely, BMFM-DNA-REF in which the model is trained with sequences of varying lengths along with their reverse complements derived from the reference genome and BMFM-DNA-SNP in which the model is trained with sequences created using a novel representation scheme that encodes sequence variations. Our findings indicate that integrating sequence variations into DNALMs helps capture the biological functions as seen in improvements on all fine-tuning tasks. To explore the model's practical utility, we experimented with various strategies for SNP imputation on promoter detection task introduced in DNABERT-2. However, we acknowledge that the current benchmarks are limited in their ability to fully evaluate these models. To enable more comprehensive assessment in the future and encourage community contributions, we release our models through HuggingFace and the code to reproduce the results at https://github.com/BiomedSciAI/biomed-multi-omic