Biology subjects

Zhong, E.

Publications and source records attributed to Zhong, E..

4 recordsLinked to original sources

bioRxiv2026

Small molecule structure elucidation from NMR spectra with generative and reasoning models

Elucidating the structures of unknown small molecules remains a major challenge in chemistry, pharmacology, and drug discovery. While nuclear magnetic resonance (NMR) spectroscopy is the gold standard for structure elucidation, interpreting spectra remains labor-intensive and requires expert knowledge to navigate the vast space of possible structures. Here, we present an AI system for rapid, automated de novo structure elucidation that combines a molecular generative model with a scientific reasoning agent. Its generative component, ChefNMR2, is an atomic flow-matching model that predicts small-molecule structures from molecular formulae and one-dimensional 1H and 13C NMR spectra. ChefNMR2-Agent augments our generative model with large language models (LLMs) to reason over and refine candidate structures. Across diverse benchmarks, ChefNMR2 substantially outperforms existing tools, offering calibrated confidence estimates and two to three orders of magnitude faster inference than frontier LLMs. We use ChefNMR2-Agent to elucidate the structures of four novel natural products, matching human-chemist accuracy in a fraction of the time. Our work demonstrates how specialized generative models and general-purpose reasoning agents can unite to solve challenging scientific inverse problems and accelerate NMR structure elucidation, thus opening new possibilities for AI-driven small-molecule discovery across diverse disciplines.

bioinformatics↗

bioRxiv2026

The CAHRA Challenge: A Community-Wide Assessment of Cryo-EM Heterogeneous Reconstruction Algorithms

The ability of cryo-electron microscopy (cryo-EM) to interrogate the atomic structure and motion of biomolecules has motivated the development of a wide range of algorithms for heterogeneity analysis. However, evaluating and comparing these methods remains challenging because ground-truth structures are generally unknown for experimental samples. Here, we introduce the 2026 Community-Wide Assessment of Heterogeneous Reconstruction Algorithms (CAHRA), a community-wide challenge centered on three benchmark datasets that probe distinct tasks in heterogeneity analysis. These include (1) compositional heterogeneity arising from mixtures of distinct protein complexes, (2) continuous conformational variability and atomic modeling, and (3) entanglement between molecular conformation and particle pose. We describe the design, construction, and validation of these datasets, as well as their use in the recently completed CAHRA Challenge.

biophysics↗

bioRxiv2020

IDseq - An Open Source Cloud-based Pipeline and Analysis Service for Metagenomic Pathogen Detection and Monitoring

BackgroundMetagenomic next generation sequencing (mNGS) has enabled the rapid, unbiased detection and identification of microbes without pathogen-specific reagents, culturing, or a priori knowledge of the microbial landscape. mNGS data analysis requires a series of computationally intensive processing steps to accurately determine the microbial composition of a sample. Existing mNGS data analysis tools typically require bioinformatics expertise and access to local server-class hardware resources. For many research laboratories, this presents an obstacle, especially in resource limited environments. FindingsWe present IDseq, an open source cloud-based metagenomics pipeline and service for global pathogen detection and monitoring (https://idseq.net). The IDseq Portal accepts raw mNGS data, performs host and quality filtration steps, then executes an assembly-based alignment pipeline which results in the assignment of reads and contigs to taxonomic categories. The taxonomic relative abundances are reported and visualized in an easy-to-use web application to facilitate data interpretation and hypothesis generation. Furthermore, IDseq supports environmental background model generation and automatic internal spike-in control recognition, providing statistics which are critical for data interpretation. IDseq was designed with the specific intent of detecting novel pathogens. Here, we benchmark novel virus detection capability using both synthetically evolved viral sequences, and real-world samples, including IDseq analysis of a nasopharyngeal swab sample acquired and processed locally in Cambodia from a tourist from Wuhan, China, infected with the recently emergent SARS-CoV-2. ConclusionThe IDseq Portal reduces the barrier to entry for mNGS data analysis and enables bench scientists, clinicians, and bioinformaticians to gain insight from mNGS datasets for both known and novel pathogens.

bioinformatics↗

bioRxiv2018

Noninvasive Vagus Nerve Stimulation Alters Neural Response and Physiological Autonomic Tone to Noxious Thermal Challenge

The mechanisms by which noninvasive vagal nerve stimulation (nVNS) affect central and peripheral neural circuits that subserve pain and autonomic physiology are not clear, and thus remain an area of intense investigation. Effects of nVNS vs sham stimulation on subject responses to five noxious thermal stimuli (applied to left lower extremity), were measured in 30 healthy subjects (n=15 sham and n=15 nVNS), with fMRI and physiological galvanic skin response (GSR). With repeated noxious thermal stimuli a group x time analysis showed a significantly (p < .001) decreased response with nVNS in bilateral primary and secondary somatosensory cortices (SI and SII), left dorsoposterior insular cortex, bilateral paracentral lobule, bilateral medial dorsal thalamus, right anterior cingulate cortex, and right orbitofrontal cortex. A group x time x GSR analysis showed a significantly decreased response in nVNS group (p < .0005) in bilaterally in SI, lower and mid medullary brainstem, and inferior occipital cortex. Finally, nVNS treatment showed decreased activity in pronociceptive brainstem nuclei (e.g. the reticular nucleus and rostral ventromedial medulla) and key autonomic integration nuclei (e.g. the rostroventrolateral medulla, nucleus ambiguous, and dorsal motor nucleus of the vagus nerve). In aggregate, noninvasive vagal nerve stimulation reduced the physiological response to noxious thermal stimuli and impacted neural circuits important for pain processing and autonomic output.

neuroscience↗