bioinformatics teams

Abstract: Single-cell foundation models (scFMs) increasingly rely on large-scale transcriptomic pretraining, yet expanding pretraining data can yield diminishing gains while substantially increasing computational cost. Our data scaling analyses showed that incorporating biological knowledge, including cell-level text annotation and gene-level regulatory information, provided additional scaling dimension than simply increasing data size. Motivated by this observation, we present scKITE, a simple yet effective scFM that integrates cell-annotation and gene-regulatory supervision into a shared transcriptomic Transformer encoder through lightweight auxiliary decoders. These decoders are used only during pretraining and subsequently discarded, yielding a general-purpose encoder enriched with biological knowledge for downstream applications. With only 179,067 pretraining samples, i.e., less than 0.5\% of those used by previous strong scFMs, scKITE outperformed these models across diverse downstream tasks, highlighting knowledge-enhanced pretraining as a promising paradigm for biologically grounded scFMs.

Abstract: We study weighted edit distance between two strings of total length $n$, where edit costs are induced by an arbitrary metric. For equal-length inputs, Kuszmaul (2019) gave an $O(n^δ)$-approximation with $\widetilde{O}(n^{2-δ})$ running time for every fixed $0 < δ< 1$. We give the first constant-factor approximation for weighted edit distance over arbitrary metrics in strongly subquadratic running time. For every $0 < \varepsilon \le 1$, our randomized algorithm runs in $\widetilde{O}(n^{7/4}/\varepsilon^8)$ time and returns a $(3+\varepsilon)$-approximation with probability at least $1-n^{-10}$. The algorithm allows unequal input lengths and places no bound on the ratio between edit costs.

Abstract: Acidophilic proteins that remain stable and functional under highly acidic conditions, are important for industrial biocatalysis, acid-related bioprocessing, and the discovery of acid-stable enzymes. However, their identification relies heavily on time-consuming experimental screening methods. With the rapid growth of protein sequence databases, the need for computational identification methods that are both accurate and efficient has become stronger. The emergence of protein language models (PLMs) has significantly improved the sequence representation of downstream biological prediction tasks. This paper proposes MI-PEFT, a mixture-of-experts integrated parameter-efficient fine-tuning framework. Built on the ESM C-600M backbone, the framework incorporates LoRA-based PEFT methods and a DeepSeekMoE-based classification head to resolve the limitations of PEFT and significantly improve computational efficiency. Notably, this task is characterized by a significant class imbalance in the dataset, making high specificity particularly challenging. The experimental results demonstrate that MI-PEFT on PLMs, especially {\text{C}}^{\text{3}}\text{A}, serves as an efficient tool for identifying acidophilic proteins and a constrained pathway that helps resolve class-imbalance by preserving the pretrained representations.

Abstract: Many scientific graphs attach several variables to each node, so a single scalar edge weight cannot describe direction-dependent interactions. We model each edge by a symmetric positive-definite (SPD) matrix and infer a posterior over matrix-valued graph geometries, which we call the Bayesian matrix-valued graph (BMVG). We ask how these interactions reconfigure across contexts: how large the change is and which multivariate directions strengthen or weaken. The geodesic distance induced by the affine-invariant Riemannian metric (AIRM) quantifies deformation magnitude and generalized eigenvalues resolve its signed directions.Against fused graphical lasso, Bayesian multiple-GGM, and common principal components, BMVG is competitive on global precision recovery while retaining identifiable matrix-valued edge structure and accurately recovering edge-level deformation directions. In controlled known-truth experiments, it resolves structural change with increasing sample size, including orientation changes that leave ordinary eigenvalues unchanged. In one year of Bay Area weather data, the geometry of 12-hour change reconfigures spatial coupling about as much as whole seasons differ. In TCGA-BRCA, estrogen-receptor (ER)-associated reconfiguration concentrates on specific gene-module pairs and persists under graph-scaffold sparsification and removal of subgroup mean differences. These results establish posterior matrix-valued edge geometry as a unified framework for quantifying and interpreting context-dependent multivariate reconfiguration.

Abstract: Automated prediction of Enzyme Commission (EC) numbers plays a central role in functional annotation and computational drug discovery. However, standard multi-label machine learning pipelines frequently rely on default decision thresholds (t=0.50), assuming balanced prior distributions across target heads. In this study, we present a systematic empirical diagnostic of uncalibrated fixed decision boundaries operating under severe class imbalance across N = 14,096 annotated compounds categorized into six primary EC classes (EC1-EC6). Our results highlight a pronounced Accuracy Paradox: while the multi-label system achieves a deceivingly high mean accuracy of 77.16%, the macro F1-score (0.3976) and macro recall (0.3872) reveal severe predictive breakdown. Majority target classes suffer from hyper-sensitivity and over-prediction, whereas minority classes exhibit sharp recall decay, culminating in a total decision boundary collapse for EC6 (Recall = 0.00%) despite underlying discriminative power (ROC-AUC = 0.5857). Feature correlation analysis further reveals high linear redundancy among topological indices relative to fingerprint density metrics. Ultimately, this diagnostic study demonstrates that standard point predictions mask critical errors in bioinformatics workflows. We establish target-specific threshold optimization and post-hoc conformal calibration as essential, open-source post-processing safeguards for reliable applied machine learning and deep learning architectures.