Weekly BioML Digest [December 29, 2025]

Machine Learning × Computational Biology paper compilation

Hey! It's your weekly automated digest of machine learning papers in CompBio and Drug Discovery. Enjoy and happy New Year!

Feedback? Email me at biomldigest@gmail.com.

📚 Section 1: Peer-Reviewed Journals (Top 20)

383 papers matched filters → 20 selected after LLM relevance + novelty ranking.

• Designing synthetic regulatory elements using the generative AI framework DNA-Diffusion
  DaSilva, Lucas Ferreira, Senan, Simon, Kribelbauer-Swietek, Judith F., Patel, Zain Munir, Louis, Lithin Karmel, Reddy, Aniketh Janardhan, Gabbita, Sameer, Rosen, Jonathan D., Nussbaum, Zach, Córdova, César Miguel Valdez, Wenteler, Aaron, Weber, Noah, Tunjic, Tin M., Mansoldo, Martino, Khan, Talha Ahmad, Hwang, Gue-Ho, Gardeux, Vincent, Humphreys, David T., Smith, Cameron, Bejan, Matei, Bromley, Peter, Connell, Will, Deplancke, Bart, Love, Michael I., Wong, Emily S., Meuleman, Wouter, Pinello, Luca — Nature Genetics, 2025-12-23
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• Stable de novo protein design via joint conformational landscape and sequence optimization
  Cho, Yehlin, Dauparas, Justas, Tsuboyama, Kotaro, Rocklin, Gabriel J., Ovchinnikov, Sergey — Nature Communications, 2025-12-24
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• MPCutter: Predicting Protease-specific Substrate Cleavage Sites Using a Protein Language Model.
  Zhe Wang, Tuoyu Liu, Guo-Qin Xu, Han Gao, Ruohan Zhang, Honglian Zhang, Guijie Zhang, N. Wu, Bin Yao, Huiying Luo, Feifei Guan, Jian Tian — Genomics, proteomics & bioinformatics, 2025-12-23
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• The Human Omnibus of Targetable Pockets
  Carpenter, Kristy A., Altman, Russ B. — Journal of Cheminformatics, 2025-12-24
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• ABT-DDI: A Graph Transformer Model with Atomic-Bond Structure Awareness for Drug-Drug Interaction Prediction.
  Xu Guo, Jianbo Qiao, Siqi Chen, Junru Jin, Ding Wang, Wenjia Gao, Feifei Cui, Zilong Zhang, Hua Shi, Zhongmin Yan, Leyi Wei, Xinbo Jiang — ACS synthetic biology, 2025-12-23
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• Proteinext: Protein Function Prediction with Sequence Embeddings and Natural Language Processing
  Hailey Ledenko, Luke Coleman, G. Alvarado, Tyler Stratton, Boen Liu, Jie Hou, Dong Si, Lei Zhang, Rui Ding, Yang Wang, Renzhi Cao — Medinformatics, 2025-12-23
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• ALyzer3D.AI: a more generalizable deep learning predictor of light chain amyloidogenicity powered by structural and evolutionary Artificial Intelligence.
  Peter May, Johannes Jung, Marion Högner, Florian Bassermann — Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis, 2025-12-26
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• SynergyGraph: predicting cell line specific drug combination synergy scores using knowledge graph representation and hypergraph modeling
  Mehrabani, Maryam, Lakizadeh, Amir, Siahpirani, Alireza Fotuhi, Salimi, Mahdieh, Zare-Mirakabad, Fatemeh, Masoudi-Nejad, Ali — Scientific Reports, 2025-12-24
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• A Comparative Study of Deep Learning and Classical Modeling Approaches for Protein-Ligand Binding Pose and Affinity Prediction in Coronavirus Main Proteases.
  Yue Liu, Haocheng Tang, Taoyu Niu, Junmei Wang — Journal of chemical information and modeling, 2025-12-23
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• High Na-Adducted Ion Selectivity in Laser Desorption/Ionization Mass Spectrometry with a Steric-Tuned COF.
  Zhichao Yan, Xiaoyan Wang, Zhenxin Wang, Yanfeng Zheng, Lingyi Zhang, Weibing Zhang — Analytical chemistry, 2025-12-25
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• Proteomic signatures of smoking and their associations with risk of incident diseases and mortality in diverse populations
  Xiao, Sihao, Liu, Bowen, Argentieri, M. Austin, Belbasis, Lazaros, Shovlin, Claire L., Collister, Jennifer A., Wang, Siyi, Hannon, Eilis, Liu, Jun, Chan, Kahung, Mosaoa, Rami Muath, Li, Liming, Lv, Jun, Yu, Canqin, Sun, Dianjianyi, Mill, Jonathan, Clarke, Robert, Hunter, David J., Bennett, Derrick, Nevado-Holgado, Alejo J., Chen, Zhengming, Amin, Najaf, van Duijn, Cornelia — Nature Communications, 2025-12-24
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• Explainable machine learning identifies immune-inflammatory biomarkers and therapeutic candidates in drug-resistant epilepsy
  Ijaz, Tayyab, Maqsood, Hamna, Rehman, Abdur, Tahir ul Qamar, Muhammad, Ashfaq, Usman Ali — Scientific Reports, 2025-12-25
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• Machine learning prediction of pediatric adverse drug reactions using consensus-derived scarce data
  Tian, Yao, Yi, Jiacai, Li, Kun, Peng, Jinfu, Deng, Youchao, Jiang, Dejun, Cao, Dongsheng — Communications Chemistry, 2025-12-26
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• Mechanics of small intestine motility for oral macromolecular delivery: modelling segmentation versus peristalsis.
  Benyamin Naranjani, Shakhawath Hossain, M. Tjakra, Pardis Azhand, Christel A. S. Bergström, Patrick Sinko, Per Larsson — Drug delivery, 2025-12-24
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• Machine learning can distinguish orphans that have resulted from sequence divergence beyond recognition
  Emilios Tassios, Jori de Leuw, Christoforos Nikolaou, A. Kupczok, Nikolaos Vakirlis — Bioinformatics Advances, 2025-12-27
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• Machine learning-guided discovery and molecular dynamics simulation of VISTA-targeted immunotherapeutics for cancer immunotherapy
  Albutti, Aqel — Naunyn-Schmiedeberg's Archives of Pharmacology, 2025-12-26
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• Prediction and analysis of anti-aging peptides using data augmentation and machine learning algorithms
  Zhang, Zhiyuan, Chen, Yuanyuan, Wang, Shihao, Chen, Guozhong, Wang, Mingyang, Pan, Yuanyuan, Li, Erguang — BMC Biology, 2025-12-24
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• Bidirectional reinforcement learning neural network for constrained molecular design
  Lin, Junan, Hostaš, Jiří, Hu, Anguang, Hu, Hang, Ooi, Hsu Kiang, Ghaemi, Mohammad Sajjad — Scientific Reports, 2025-12-24
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• FourierMIL: Fourier Filtering-based Multiple Instance Learning for Whole Slide Image Analysis
  Zheng, Yi, Sharma, Harsh, Betke, Margrit, Cherry, Jonathan D., Mez, Jesse B., Beane, Jennifer E., Kolachalama, Vijaya B. — International Journal of Computer Vision, 2025-12-28
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• Methods in PES-Learn: Direct-Fit Machine Learning of Born–Oppenheimer Potential Energy Surfaces
  Ian T Beck, J. Turney, Henry F. Schaefer — Molecules, 2025-12-25
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🧬 Section 2: Preprints (arXiv + bioRxiv)

113 papers matched filters → 20 selected after LLM relevance + novelty ranking.

• 📄 Drug-like antibodies with low immunogenicity in human panels designed with Latent-X2
  Latent Labs Team, Henry Kenlay, Daniella Pretorius, Jonathan Crabbé, Alex Bridgland, Sebastian M. Schmon, Agrin Hilmkil, James Vuckovic, Simon Mathis, Tomas Matteson, Rebecca Bartke-Croughan, Amir Motmaen, Robin Rombach, Mária Vlachynská, Alexander W. R. Nelson, David Yuan, Annette Obika, Simon A. A. Kohl — arXiv, 2025-12-23
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• 🧬 A foundational model for joint sequence-function multi-species modeling at scale for long-range genomic prediction
  Boshar, S.; Evans, B.; Tang, Z.; Picard, A.; Adel, Y.; Lorbeer, F. K.; Rajesh, C.; Karch, T.; Sidbon, S.; Emms, D.; Mendoza-Revilla, J.; Al-Ani, F.; Seitz, E.; Schiff, Y.; Bornachot, Y.; Hernandez, A.; Lopez, M.; Laterre, A.; Beguir, K.; Koo, P.; Kuleshov, V.; Stark, A.; de Almeida, B. P.; Pierrot, T. — bioRxiv, 2025-12-25
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• 🧬 To Predict is to Design: Unlocking Generative Capabilities in All-Atom Structure Predictors via Geometric Score Distillation
  Li, Y.; Su, Y.; Jing, Y.; Liu, T. — bioRxiv, 2025-12-26
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• 🧬 Generative inverse design of RNA structure and function with gRNAde
  Joshi, C. K.; Gianni, E.; Kwok, S. L. Y.; Mathis, S. V.; Lio, P.; Holliger, P. — bioRxiv, 2025-12-26
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• 🧬 Unexplored regions of the protein sequence-structure map revealed at scale by a library of foldtuned language models
  Subramanian, A. M.; Martinez, Z. A.; Lourenco, A. L.; Yuan, S. C.; Liu, S.; Wang, T.-Y.; Chou, T.-F.; Thomson, M. — bioRxiv, 2025-12-26
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• 🧬 Improved multimodal protein language model-driven universal biomolecules-binding protein design with EiRA
  Zeng, W.; Zou, H.; Li, X.; Dou, Y.; Wang, X.; Peng, S. — bioRxiv, 2025-12-23
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• 🧬 GenoME: a MoE-based generative model for individualized, multimodal prediction and perturbation of genomic profiles
  Wei, J.; Xue, Y.; Chai, H.; Gao, Y. Q. — bioRxiv, 2025-12-28
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• 🧬 GenVS TBDB: A Target-Aware AI-Generated andVirtual Screened Small-Molecule Library for Tuberculosis Drug Discovery
  Lv, X.; Guo, H.; Wang, J.; Hu, Q.; zhang, M.; Wang, H.; Xiao, G.; Zheng, X.; Lu, X.; Tang, Z.; Yu, K.; Xu, G.; Chen, S.; Zhang, R.; Guo, J. — bioRxiv, 2025-12-23
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• 🧬 Adapting Co-Folding Models for Structure-Based Protein-Protein Docking Through Flow Matching
  Xu, D.; Chu, L.-S.; Gray, J. J. — bioRxiv, 2025-12-23
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• 🧬 Sampling Function-Related Metastable States of Proteins With DASH
  Zha, J.; Zheng, Z.; Zhong, J.; Wang, W.; Shen, Q.; Li, Q.; Li, M.; Wu, C.; Xiao, Q.; Ren, Q.; Li, N.; Zhang, H.; Liu, X.; Feng, L.; Qin, W.; Zhang, J. — bioRxiv, 2025-12-25
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• 🧬 An interpretable neural network unveils higher-order epistasis in large protein sequence-function relationships
  Sethi, P.; Zhou, J. — bioRxiv, 2025-12-23
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• 🧬 PlantCAD2: A Long-Context DNA Language Model for Cross-Species Functional Annotation in Angiosperms
  Zhai, J.; Gokaslan, A.; Hsu, S.-K.; Chen, S.-P.; Liu, Z.-Y.; Marroquin, E.; Czech, E.; Cannon, B.; Berthel, A.; Romay, C.; Pennell, M.; Kuleshov, V.; Buckler, E. S. — bioRxiv, 2025-12-23
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• 🧬 Predicting interaction-specific protein-protein interaction perturbations by missense variants with MutPred-PPI
  Stewart, R.; Laval, F.; Coppin, G.; Spirohn-Fitzgerald, K.; Tixhon, M.; Hao, T.; Calderwood, M. A.; Mort, M.; Cooper, D. N.; Vidal, M.; Radivojac, P. — bioRxiv, 2025-12-23
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• 🧬 FlashAffinity: Bridging the Accuracy-Speed Gap in Protein-Ligand Binding Affinity Prediction
  Jiang, S.; Chen, Y.; Cao, Z.; Jin, W. — bioRxiv, 2025-12-25
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• 🧬 Integrating NMR restraints into coarse-grained simulations: toward accurate conformational ensembles of complex protein systems
  Cullen, M.; Biancaniello, C.; Taskova, K.; Miletic, V.; Mercadante, D.; De Simone, A. — bioRxiv, 2025-12-24
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• 📄 From In Silico to In Vitro: Evaluating Molecule Generative Models for Hit Generation
  Nagham Osman, Vittorio Lembo, Giovanni Bottegoni, Laura Toni — arXiv, 2025-12-26
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• 🧬 PocketX: Preference Alignment for Protein Pockets Design through Group Relative Policy Optimization
  Fan, Y.; He, Z.; Li, B.; He, B.; Zhang, M.; Zhang, J.; Zhang, H. — bioRxiv, 2025-12-28
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• 🧬 Biophysically Grounded Deep Learning Improves Protein-Protein ΔΔG Prediction
  Feldman, J.; Maechler, A.; Wang, D.; Shakhnovich, E. — bioRxiv, 2025-12-25
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• 🧬 DeepAden: an explainable machine learning for substrate specificity prediction in nonribosomal peptide synthetases
  Huang, J.; Ge, L.; Wu, Y.; Meng, S.; Tian, Y.; Wu, J.; Gao, Q.; Li, P.; Zhang, H.; Qin, Z. — bioRxiv, 2025-12-23
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• 🧬 Large scale prospective evaluation of co-folding across 557 Mac1-ligand complexes and three virtual screens
  Kim, J.; Correy, G. J.; Hall, B. W.; Rachman, M. M.; Mailhot, O.; Togo, T.; Gonciarz, R. L.; Jaishankar, P.; Neitz, R. J.; Hantz, E. R.; Doruk, Y. U.; Stevens, M. G. V.; Diolaiti, M. E.; Reid, R.; Gopalkrishnan, S.; Krogan, N. J.; Renslo, A. R.; Ashworth, A.; Shoichet, B. K.; Fraser, J. S. — bioRxiv, 2025-12-28
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