Cross-Granularity Representations for Biological Sequences: Insights from ESM and BiGCARP

Recent advances in general-purpose foundation models have stimulated the development of large biological sequence models. While natural language shows symbolic granularity (characters, words, sentences), biological sequences exhibit hierarchical granularity whose levels (nucleotides, amino acids, protein domains, genes) further encode biologically functional information. In this paper, we investigate the integration of cross-granularity knowledge from models through a case study of BiGCARP, a Pfam domain-level model for biosynthetic gene clusters, and ESM, an amino acid-level protein language model. Using representation analysis tools and a set of probe tasks, we first explain why a straightforward cross-model embedding initialization fails to improve downstream performance in BiGCARP, and show that deeper-layer embeddings capture a more contextual and faithful representation of the model's learned knowledge. Furthermore, we demonstrate that representations at different granularities encode complementary biological knowledge, and that combining them yields measurable performance gains in intermediate-level prediction tasks. Our findings highlight cross-granularity integration as a promising strategy for improving both the performance and interpretability of biological foundation models.

Disentangling Similarity and Relatedness in Topic Models

The recent advancement of large language models has spurred a growing trend of integrating pre-trained language model (PLM) embeddings into topic models, fundamentally reshaping how topics capture semantic structure. Classical models such as Latent Dirichlet Allocation (LDA) derive topics from word co-occurrence statistics, whereas PLM-augmented models anchor these statistics to pre-trained embedding spaces, imposing a prior that also favours clustering of semantically similar words. This structural difference can be captured by the psycholinguistic dimensions of thematic relatedness and taxonomic similarity of the topic words. To disentangle these dimensions in topic models, we construct a large synthetic benchmark of word pairs using LLM-based annotation to train a neural scoring function. We apply this scorer to a comprehensive evaluation across multiple corpora and topic model families, revealing that different model families capture distinct semantic structure in their topics. We further demonstrate that similarity and relatedness scores successfully predict downstream task performance depending on task requirements. This paper establishes similarity and relatedness as essential axes for topic model evaluation and provides a reliable pipeline for characterising these across model families and corpora.