Background: Bispecific T-cell Engagers (TCEs) targeting B7H3 (CD276) show promise for solid tumors but are limited by systemic toxicities and poor tumor penetration. Intratumoral (IT) delivery is proposed as a solution, but the safety and spatial pharmacodynamics (PD) remain poorly defined in these malignancies. Spontaneous canine tumors serve as a highly translatable model for human […]

Pancreatic ductal adenocarcinoma (PDAC) is a deadly, highly metastatic disease, driven by an interplay between cancer cells and the metastatic site-specific microenvironment. However, pre-clinical models that robustly capture these interactions within the context of matched primary and metastatic tumors are limited. Here, we present a novel transplant model system for matched pancreas and liver tumors […]

ProteomeLM is a proteome-scale language model trained on proteomes spanning the tree of life to reconstruct masked protein embeddings from proteome context within each species. Its attention coefficients capture protein-protein interactions without supervision. Here, we show that this capability extends to cross-species host-pathogen interactions (HPI) across ten human pathogen taxa spanning viruses and bacteria, and […]

Accurate prioritization of T-cell receptor (TCR)-epitope interactions and identification of tumor-reactive T cells are important but difficult steps in immunotherapy-oriented bioinformatics workflows. Existing methods typically address these tasks separately and either model TCR-epitope pairs as independent observations or rely primarily on transcriptomic signatures. In this study, we present TRACE (TCR-epitope pRioritization And T-Cell idEntification), a […]

Transcription terminators are universal landmarks that delimit RNAs and tune downstream gene expression, yet the sequence rules that define them remain elusive. The classical model of bacterial intrinsic termination – an RNA hairpin followed by a uracil-rich tract – is incomplete, as stem-preserving mutations can abolish termination. By precisely mapping termination sites across 10^4 sequences, […]

Migraine headaches affect over one billion people internationally and can be defined as episodes of acute severe pain wrapping around the head and are normally accompanied by nausea, blurry vision, and sensitivity to light and sound. While triggers that cause migraines may vary among patients, evidence shows they are involved with the trigeminovascular system (a […]

Clear cell renal cell carcinoma (ccRCC) is characterized by transcriptional reprogram-ming driven by hypoxia signaling, metabolic rewiring, and immune modulation. While gene-level analyses have defined key features of ccRCC biology, they do not capture isoform-level variation arising from alternative splicing. Differential transcript usage (DTU) represents an additional regulatory layer that may influence protein function, pathway […]

Background: Thoracic aortic aneurysm (TAA) is a life-threatening condition with an unpredictable lisk of rupture. Current clinical parameters have limited ability to accurately predict imminent rupture. Osteopontin (OPN) has been implicated in aortic aneurysm pathology, however, it role as a marker of imminent rupture remains. unclear. We investigated the dynamics of OPN expression dynamics in […]

Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron (MN) loss, muscle atrophy and paralysis. Although traditionally considered a MN-specific disease, accumulating evidence supports a crucial contribution of skeletal muscle pathology to disease onset and progression. Except for specific mutations, to date there is no effective treatment for ALS. […]

Context: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy often diagnosed at advanced stages due to the lack of early clinical symptoms. DNA methylation alterations arise early in PDAC tumorigenesis and may serve as promising biomarkers for blood-based cancer detection. Objective: To evaluate the performance of EPISEEK, a laboratory-developed blood-based multi-cancer early detection (MCED) assay, […]

Photoreceptor degeneration drives electrophysiological remodeling in downstream retinal neurons, including hyperactive firing of retinal ganglion cells (RGCs) that degrades residual vision. Although Retinoic Acid (RA) and its receptor (RAR) are known to upregulate ion channel genes associated with RGC hyperactivity, these genes lack canonical RAR binding sites required for direct transcriptional regulation. Here, we identify […]

Most human genes produce multiple RNA isoforms, yet it remains unclear which isoforms are translated into stable, functional proteins. Long-read RNA-sequencing resolves full-length transcript structures and, when paired with mass spectrometry, can provide empirical evidence of isoform translation. Despite this opportunity, comprehensive workflows integrating isoform discovery, open reading frame prediction, peptide identification, and protein inference […]