arXiv:2506.14861v2 Announce Type: replace
Abstract: Transcriptomic foundation models pretrained with masked language modeling can achieve low pretraining loss yet produce poor cell representations for downstream tasks. We introduce whole-cell expression decoding (WCED), where models reconstruct the entire gene vocabulary from a single CLS token embedding, even with limited inputs, creating a maximally informative bottleneck. WCED consistently outperforms MLM on all downstream metrics despite higher reconstruction error during training. Gene-level error tracking reveals that both methods preferentially learn genes whose expression co-varies with stable transcriptional programs rather than those driven by transient factors. We further add hierarchical cross-entropy loss that exploits Cell Ontology structure for zero-shot annotation at multiple granularity levels. Models trained with these objectives achieve best overall performance across CZI benchmarks, on zero-shot batch integration and linear probing cell-type annotation. Methods are implemented in biomed-multi-omic ( https://github.com/BiomedSciAI/biomed-multi-omic ), an open-source framework for transcriptomic foundation model development.
Depression subtype classification from social media posts: few-shot prompting vs. fine-tuning of large language models
BackgroundSocial media provides timely proxy signals of mental health, but reliable tweet-level classification of depression subtypes remains challenging due to short, noisy text, overlapping symptomatology,