Shuijin Lin, Shaozhen Yan, Tuo Liu, Haifeng Wang, Chunfeng Lian, Jie Lu, Jianhua Ma, Lin Xie
The biological definition of Alzheimer's disease (AD) relies on multi-modal neuroimaging, yet the clinical utility of positron emission tomography (PET) is limited by cost and radiation exposure, hindering early screening at preclinical or prodromal stages. While generative models offer a promising alternative by synthesizing PET from magnetic resonance imaging (MRI), achieving subject-specific precision remains a primary challenge. Here, we introduce DIReCT$++$, a Domain-Informed ReCTified flow model for synthesizing multi-tracer PET from MRI combined with fundamental clinical information. Our approach integrates a 3D rectified flow architecture to capture complex cross-modal and cross-tracer relationships with a domain-adapted vision-language model (BiomedCLIP) that provides text-guided, personalized generation using clinical scores and imaging knowledge. Extensive evaluations on multi-center datasets demonstrate that DIReCT$++$ not only produces synthetic PET images ($^{18}$F-AV-45 and $^{18}$F-FDG) of superior fidelity and generalizability but also accurately recapitulates disease-specific patterns. Crucially, combining these synthesized PET images with MRI enables precise personalized stratification of mild cognitive impairment (MCI), advancing a scalable, data-efficient tool for the early diagnosis and prognostic prediction of AD. The source code will be released on https://github.com/ladderlab-xjtu/DIReCT-PLUS.
Weicai Long, Yusen Hou The Hong Kong University of Science and Technology (Guangzhou), Junning Feng, Houcheng su Hong Kong University of Science and Technology, Shuo Yang, Donglin Xie, Yanlin Zhang The Hong Kong University of Science and Technology (Guangzhou)
Large Language Models (LLMs) are increasingly adopted as conversational assistants in genomics, where they are mainly used to reason over biological knowledge, annotations, and analysis outputs through natural language interfaces. However, existing benchmarks either focus on specialized DNA models trained for sequence prediction or evaluate biological knowledge using text-only questions, leaving the behavior of general-purpose LLMs when directly exposed to raw genome sequences underexplored. We introduce GenomeQA, a benchmark designed to provide a controlled evaluation setting for general-purpose LLMs on sequence-based genome inference tasks. GenomeQA comprises 5,200 samples drawn from multiple biological databases, with sequence lengths ranging from 6 to 1,000 base pairs (bp), spanning six task families: Enhancer and Promoter Identification, Splice Site Identification, Taxonomic Classification, Histone Mark Prediction, Transcription Factor Binding Site Prediction, and TF Motif Prediction. Across six frontier LLMs, we find that models often outperform random baselines, particularly on tasks driven by local sequence cues such as GC content and short motifs, while performance degrades on tasks that require more indirect or multi-step inference over sequence patterns. GenomeQA establishes a diagnostic benchmark for studying and improving the use of general-purpose LLMs on raw genomic sequences.
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cs.CL
Proceedings of the 64th Annual Meeting of the Association for Computational Linguistics (Volume 1: Long Papers) · 2026 · 正式发表