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An expanded codebook of human transcription factor DNA-binding specificity

Nature Bioinformatics AI Arttu Jolma, Kaitlin U. Laverty, Ali Fathi, Ally W. H. Yang, Isaac Yellan, Ilya E. Vorontsov, Antoni J. Gralak, Judith F. Kribelbauer-Swietek, Sachi Inukai, Rozita Razavi, Mihai Albu, Alexander Brechalov, Zain M. Patel, Vladimir Nozdrin, Georgy Meshcheryakov, Andrey Buyan, Ivan Kozin, Sergey Abramov, Alexandr Boytsov, Fedor A. Kolpakov, Vsevolod J. Makeev, Marjan Barazandeh, Zhenfeng Deng, Chun Hu, Samuel A. Lambert, Sara E. Pour, Mikhail Salnikov, Hong Zheng, Giovanna Ambrosini, Judith F. Kribelbauer-Swietek, Marie-Luise Plescher, Semyon Kolmykov, Ivan Yevshin, Nikita Gryzunov, Mikhail Nikonov, Arsenii Zinkevich, Katerina Faltejskova, Pavel Kravchenko, Vasilii Kamenets, Dmitry Penzar, Anton Vlasov, Aldo Hernandez-Corchado, Hamed S. Najafabadi, Xiaoting Chen, Quaid Morris, Matthew T. Weirauch, Oriol Fornes, Vsevolod J. Makeev, Jan Grau, Ivo Grosse, Philipp Bucher, Bart Deplancke, Ivan V. Kulakovskiy, Timothy R. Hughes 2026-08-05

TL;DR - A Nature paper reports an expanded reference codebook of human transcription factor (TF) DNA-binding specificities, derived from a panel of complementary assays and adding more than 100 new motifs. It matters because motif catalogues are the core training and annotation resource for regulatory-genomics models that predict binding sites, enhancer activity and variant effects.

Multiple assay types were combined, each probing a different aspect of DNA sequence specificity, rather than relying on a single binding-assay modality.
The result is >100 previously uncharacterized motifs, extending coverage to putative/unvalidated human TFs that lacked known binding preferences.
Broader motif coverage directly improves downstream computational tasks: motif scanning, regulatory-element annotation, and interpretation of noncoding variants.
Content is thin (abstract-level only) — no details are given here on assay names, TF counts, model architectures, or validation metrics; the above is inferred from the published summary.

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