biotech companies

Abstract: Predicting spatial gene expression from routine H&E histology offers a scalable route toward spatial molecular profiling. Recent work has pursued increasingly sophisticated architectures to capture spatial context and richer expression structure. At the same time, simple estimators have shown strong performance in several studies, but what they already solve and where additional complexity is needed remain unclear. We study this behavior through the structure of prediction error under the mean-squared error (MSE) objective. Differences in average expression across genes can account for a substantial part of aggregate prediction performance, while a key unresolved error lies in recovering variation within each slide. Decomposing MSE into slide-level and within-slide components, we find that the within-slide component has lower residual-normalized parameter sensitivity in controlled neural experiments. This motivates Component-Guided Loss (CGL), which increases supervision of the within-slide component. CGL-Linear is a closed-form affine instantiation that achieves overall state-of-the-art performance across HEST-1k cohorts and gene-panel sizes. The same within-slide supervision improves existing neural models. These results suggest that substantial gains can come from aligning the training objective with prediction-error structure rather than increasing model complexity.

Abstract: De novo peptide sequencing from tandem mass spectra is essential for identifying peptides without relying on reference databases. Despite advances in deep learning, accurate sequencing remains challenging because experimental spectra are often sparse, noisy, and incomplete, leaving informative b- and y-ion fragments unobserved. Existing methods attempt to recover this missing evidence via latent-space imputation before autoregressive decoding. However, they typically treat imputation as a fixed reconstruction task, without considering which missing fragments are most relevant to decoder errors. Moreover, existing peak representations do not explicitly model mass differences between peaks, despite their fundamental importance. We introduce GyroNovo, a framework with two main contributions. First, we use decoder errors observed during training to adapt the imputation objective, prioritizing fragments associated with frequent decoding errors. We further use the decoder error distribution to construct easy and hard augmented views of each spectrum, enabling the decoder to learn under varying degrees of spectral corruption and missing-fragment severity. Second, we introduce a mass-aware inductive bias into self-attention by using rotary embeddings to encode pairwise mass differences between spectral peaks. Together, these components align missing-fragment recovery with decoder behavior while explicitly incorporating the mass relationships that underlie peptide fragmentation. At inference time, GyroNovo retains a standard encoder-imputer-decoder architecture and requires neither additional inputs nor auxiliary search procedures. Experiments on NovoBench show gains of about 9 percentage points in peptide-level precision and 7 percentage points in amino-acid-level precision over the state-of-the-art baseline. Code: https://github.com/UBC-NLP/gyronovo.