Biotech

Biotech executives reveal concerns over Chinese biotech, the profitability of AI, and the durability of Trump's drug price moves.

In this edition of STAT's AI Prognosis: Brittany Trang brings the latest from BIO on how biotech companies are approaching artificial intelligence.

While WGS-based AMR prediction has reached high accuracy, existing models lack a mechanism to ground neural attributions in established biological pathways. We present KG-TRACE, a novel neuro-symbolic framework that integrates the WHO mutation knowledge graph (KG) as a structured biological constraint on a neural genomic model. Unlike existing methods that learn statistical patterns in isolation, KG-TRACE fuses genomic features and RotatE-based KG embeddings through a learned epistemic trust gat

At least two new start-up companies, Preventive and Origin Genomics, say they are developing strategies that combine gene editing with in vitro fertilization to correct disease-causing mutations. Advocacy groups for people living with these genetic disorders have been quiet on the developments.

We present JEDEL, a framework for generating synthesis-ready DNA-encoded libraries (DELs) directly from three-dimensional pharmacophore representations of active ligands. JEDEL is the first model to map pharmacophore interaction patterns to actionable, scalable synthesis instructions, enabling the design of targeted libraries comprising potentially millions of molecules. Unlike existing generative approaches that produce virtual compounds requiring downstream synthesis planning, JEDEL operates w

Graph-based representations are widely used in protein modeling, yet many existing approaches rely primarily on sequence adjacency or geometric proximity, which only partially reflect the principles governing protein folding. Proteins instead adopt complex three-dimensional conformations organized around secondary structure elements, such as $α$-helices and $β$-sheets, which encode recurring local motifs and stabilizing hydrogen-bond interactions. In this work, we introduce a secondary-structure

Clustering is fundamental to scRNA-seq analysis, serving as a cornerstone for identifying cell populations and resolving tissue heterogeneity. However, existing methods focus on mining numerical statistical patterns, suffering from semantic agnosticism by neglecting the intrinsic biological functions encoded by genes. While Large Language Models (LLMs) offer promising semantic capabilities, their direct adaptation to cell clustering is hindered by the structural mismatch between generative pre-t

AI alignment, interpretability, steering, and neural perturbation studies identify order-inducing objects. We argue that order is not control. Control requires a receiver-gated response law: a denominator-indexed operator mapping material state, action/drive, bath, and receiver state to response displacement, sinks, effort, and basin projection. We identify it across biological, LLM, adapter, and stochastic-operator panels. The laws are local: an intervention can be admitted, saturated, sign-cha

I discuss some quantitative representations of Promise Theory for processes involving autonomous agents. Agent models are common in software systems, machine learning, and biology, for example, but may also apply to physics and other forms of engineering. I describe how Bayesian probability and information theoretic optimization, including Active Inference, may be incorporated with promise semantics -- as well as how Promise Theory supplements solutions, helping to avoid probability's pitfalls,

Veterinary pharmacovigilance systems are essential for monitoring adverse drug events (ADEs), yet existing approaches often fail to capture region-specific toxicity patterns shaped by local biological and regulatory contexts. In Japan, these challenges are amplified by species-specific metabolic differences and reporting practices defined by the Ministry of Agriculture, Forestry, and Fisheries (MAFF). Most prior work relies on prediction-oriented models, limiting mechanistic interpretability. Th

A central goal of biomedicine is to understand, predict and ultimately control the dynamic mechanisms by which biological systems respond to perturbations, disease progression and therapeutic intervention. Although foundation models and large language models have accelerated biomedical data interpretation, most current systems remain focused on static pattern recognition rather than prospective simulation of biological futures. Here we propose biomedical world models as a paradigm for AI-driven

Deep reinforcement learning (DRL) is increasingly applied to de novo molecular design, but choices in data, rewards, and evaluation can yield uneven performance across disease areas and chemotypes. Despite this, there is no concise synthesis of how fairness is defined, measured, and tested in DRL-based drug discovery. In this rapid evidence review, we synthesize fairness definitions and metrics for DRL-driven molecule generation in healthcare. We focus on three questions: (i) how dataset composi

Accurate prediction of protein-protein interaction sites (PPIS) is essential for understanding cellular processes, disease mechanisms, and therapeutic target discovery. Graph-based deep learning has advanced PPIS prediction by incorporating residue-level structural context. However, most graph-based models still rely on fixed propagation schemes that treat all residues similarly, despite the structural and functional heterogeneity of protein interfaces. Such propagation may limit the ability to

AI for scientific discovery is entering an agentic era, where protein-engineering systems are expected to prioritize future wet-lab experiments rather than merely fit static measurements. We introduce TadA-Bench, a million-variant wet-lab replay benchmark from 31 TadA directed-evolution rounds for future-round discovery toward agentic protein engineering. TadA-Bench preserves the campaign chronology and defines a fixed-data replay task: given earlier experimental rounds, models rank variants tha

Multimodal alignment of histopathology encoders with transcriptomic and genomic data has been shown to significantly improve performance in downstream diagnostic tasks. Hematological cytology is unique in that visual single-cell evaluation is often paired with cytogenetics and molecular genetics for blood cancer diagnosis. In this study, we present a framework to align single white blood cell images with chromosomal aberrations (karyotype) and somatic mutations from targeted gene panels. Our tra

Across machine learning, biology, and physics, independently evolving systems often converge toward strikingly similar high-level structures despite radically different microscopic details. Grokking circuits converge across random seeds, evolutionary lineages rediscover similar metabolic solutions, and renormalization flows approach common fixed points. We propose the Hierarchical Emergence Framework (HEF) as a candidate universality framework for such convergence phenomena. HEF models emergence

Light sheet fluorescence microscopy (LSM) enables high-resolution, three-dimensional (3D) imaging of biological specimens, providing rich volumetric data for studying cellular organization, pathology, and vascular networks. However, the size, dimensionality, and annotation burden of LSM data make supervised deep learning approaches costly and difficult to scale. Additionally, despite the abundance of unannotated LSM volumes, foundation models for this modality remain underexplored due to computa

The generation of accurate 3D molecular conformations is a pivotal challenge in computational chemistry and drug discovery. Recently, diffusion and flow matching models have achieved remarkable success. However, there is a critical misalignment between their mathematical formulation and the physical reality of molecules. Existing approaches predominantly treat molecules as unstructured point clouds in Cartesian space, overlooking the intrinsic hierarchical mechanics where bond lengths and bond a

Retinal imaging provides a non-invasive window into systemic microvascular health and has emerged as a potential biomarker for systemic diseases. However, whether retinal features encode biologically meaningful systemic signals that can be reliably interpreted using explainable artificial intelligence (XAI) remains unclear. An explainable multi-task deep learning framework was developed to investigate associations between retinal microvascular features and systemic abnormalities in Type 2 Diabet

Enzyme-reaction retrieval is a fundamental problem in computational biology, underpinning enzyme characterization, reaction mechanism elucidation, and the rational design of metabolic pathways and biocatalysts. As a bidirectional task, it entails both enzyme-to-reaction and reaction-to-enzyme mapping. However, existing approaches suffer from poor generalization across tasks and distributions, with performance highly sensitive to dataset splits and substantial asymmetry between retrieval directio

Biological systems are governed by structured molecular interactions, where pathways, regulatory circuits, and functional gene relationships shape cellular behavior and disease progression. Much of this knowledge is naturally represented as graphs. However, most biomedical AI models cannot directly use graph-encoded biological knowledge and instead require compressed low-dimensional representations, which can lose important structure and reduce performance, especially in limited-sample clinical

Recent advances in generative modeling show that pretrained representations can improve generation as conditioning features or alignment targets. Motivated by this, we study protein representations for predicting structures beyond conventional function annotation. We propose TriProRep, a structure-aware pretraining method that jointly models three aligned residue-level views: amino-acid identity, backbone geometry, and local full-atom geometry, discretely encoded via VQ-VAE tokenizers. By pretra

Adverse Outcome Pathways (AOP) are logic models that causally link biological mechanisms that can be measured in a lab to adverse outcomes, relevant to chemical regulatory endpoints. AOPs contextualize new approach methodologies (NAMs), in vitro and in silico methods used as alternatives to animal testing and the sequential events in an AOP serve as multi-scale models spanning biological scales. The AOP-Wiki serves as the global repository for AOPs. While the AOP-Wiki has played a central role i

Protein-protein interactions (PPIs) govern nearly all cellular processes, yet computational methods for identifying binding partners typically produce ranked predictions without mechanistic justification. This creates a fundamental barrier to adoption because biologists cannot assess whether predictions reflect genuine biochemical insight or spurious correlations. We present \textbf{Protein Thoughts}, a framework that reformulates PPI discovery as an interpretable search problem with explicit re

Adaptive decision-making in biological and artificial intelligence requires balancing the exploitation of known outcomes with the exploration of uncertain alternatives. Although prior work suggests that uncertainty generally promotes exploration, it has typically treated distinct sources of environmental uncertainty as equivalent. We consider environments with latent reward states that drift over time (volatility) and are observed through noisy outcomes (stochasticity). Both increase posterior u

Surrogate Safety Measures (SSMs) are extensively utilised in the evaluation of traffic risk in automated driving contexts. However, the majority of SSM-based evaluations employ fixed thresholds that fail to capture the human response to sustained borderline conditions or the reaction to brief, high-risk peaks. The present work proposes a biologically inspired reinterpretation of SSM thresholds. This is modelled as spiking thresholds of leaky integrate-and-fire (LIF) neurons, with multiple SSM in

Time series classification (TSC) of biological signals has progressed from handcrafted, modality-specific approaches to deep architectures capable of representing the diverse waveform structures of underlying physiological processes (i.e., morphology). This review introduces a unified morphology--modality framework that connects waveform structure to a methodological design, revealing how spikes, bursts, oscillations, slow drift, and hierarchical rhythms inform model design. By analyzing electro

Predicting spatial gene expression from routine H\&E enables large-scale molecular profiling, yet current models treat this as isolated pointwise tasks, thereby overlooking essential biological structures like gene coordination and spatial distribution. To preserve these relationships, we introduce \textbf{FLAG}, a diffusion-based framework that redefines this task as structured distribution modeling. At the same time, we identify the critical \textbf{Gene Dimension Curse}, where joint modeling

Electrocardiogram (ECG)-based models have achieved strong performance in diagnostic tasks, yet they remain limited in modeling how cardiac dynamics evolve under external interventions. In particular, existing approaches focus primarily on static prediction and lack mechanisms to capture ECG variations under different pharmacological conditions. In this work, we propose an ECG World Model for action-conditioned predictive simulation of cardiac electrophysiology. Moving beyond disjoint pipelines,

Clinical decision-making is a feedback system where risk estimates influence treatment, which in turn changes disease trajectories, and both shape clinicians' measurement practices. Static prediction often fails clinically: models trained on observational care logs conflate disease biology with clinician behavior, particularly under treatment confounder feedback and irregular or informative observation. This Review focuses on intervention-aware disease trajectory modeling in clinical AI--methods

Scientific and technological frontiers advance through punctuated dynamics, yet the principles governing these dynamics remain poorly understood. Here we collect and analyze datasets tracking the evolution of frontiers across 9 different domains, spanning materials discovery, structural biology, AI, computational biomedicine, data science, theoretical computer science, Formula-1 racing, and physical wheel building. Analyzing 6.8M solutions to 6.7K tasks, we uncover three universal patterns: (1)

Proteins perform their biological functions through three-dimensional structures encoded by amino acid sequences, and ligand-binding protein co-design requires models that generate sequence-structure compatible proteins under explicit ligand constraints. Although continuous diffusion and flow-based models support ligand-aware design in coordinate or latent spaces, existing discrete diffusion protein language models mainly operate over sequence or structure tokens without direct small-molecule co

Characterizing the physiological life boundaries of microbial strains, including viable temperature, pH, salinity, substrate utilization, and morphology, is central to biotechnology and ecology, yet traditionally requires exhaustive in vitro screening. Existing computational approaches either treat physiological traits as isolated supervised targets or repurpose biological foundation models as static encoders, leaving the genotype-to-physiology gap largely unbridged. We formulate microbial life-

Acquisition differences across sites, scanners, and protocols in dMRI introduce variability that complicates structural connectome analysis. This motivates deep learning models that can represent high-dimensional connectomes in a low-dimensional space while explicitly separating acquisition-related effects from biological variation. Conventional dimensionality reduction methods model all variance as continuous, so acquisition effects often get absorbed into a continuous latent space. Recent hybr

Hypergraphs provide a natural framework to model higher-order interactions in scientific, social, and biological systems. Hypergraph neural networks (HGNNs) aim to learn from such data, yet it remains unclear which higher-order structures these models can represent. We show that hypergraph expressivity is governed by which small patterns an architecture can detect and count. We formalize this via homomorphism densities, which measure how often a structural motif appears in a hypergraph. Combinin

The design of RNA molecules that interact with specific proteins is a critical challenge in experimental and computational biology. Despite recent progress in natural language modeling and deep learning-based protein design, there remains significant room to improve the frequency of successful interactions and the authenticity of generated sequences for functional applications. In this work, we frame conditional RNA sequence generation as a multi-stage alignment problem, introducing Moirain: a s

Recent advances in machine learning and large-scale biological data collections have revived the prospect of building a virtual cell, a computational model of cellular behavior that could accelerate biological discovery. One of the most compelling promises of this vision is the ability to perform in silico phenotypic screens, in which a model predicts the effects of cellular perturbations in unseen biological contexts. This task combines heterogeneous textual inputs with diverse phenotypic outpu

Designing proteins with desired functions or properties represents a core goal in synthetic biology and drug discovery. Recent advances in protein language models (PLMs) have enabled the generation of highly designable protein sequences, while preference alignment provides a promising way to steer designs toward desired functions and properties. Nevertheless, they often trigger catastrophic forgetting of pretrained knowledge, degrading basic designability and failing to balance multiple competin

Artificial agents now generate behavior rich enough to invite trust, surprise, and concern, yet our evaluation tools still privilege capability scores over psychological structure. This paper argues that the philosophical impasse between two symmetrical errors (Artificial Mind Blindness, which dismisses psychological organization in non-biological systems, and Artificial Mind Projection, which infers human-like inner life from fluent behavior alone) can be circumvented not by resolving the consc

AI is transforming life sciences research at unprecedented speed, accelerating discovery across protein structure prediction, genome modeling, and drug development (Jumper et al., 2021; Mak et al., 2024). Yet this rapid advancement, coupled with the open science movement, introduces significant dual-use research concerns that have received limited empirical scrutiny. Here we present the first systematic analysis of dual-use research of concern (DURC) content on open preprint servers. We screened