Generative Artificial Intelligence in Bioinformatics: A Systematic Review of Models, Applications, and Methodological Advances

Wasimul Karim; Riasad Alvi; Sayeem Been Zaman; Arefin Ittesafun Abian; Mohaimenul Azam Khan Raiaan; Saddam Mukta; Md Rafi Ur Rashid; Md Rafiqul Islam; Yakub Sebastian; Sami Azam

doi:10.1007/s11831-026-10743-z

arXiv · 2511.03354

Generative Artificial Intelligence in Bioinformatics: A Systematic Review of Models, Applications, and Methodological Advances

Wasimul Karim·Riasad Alvi·Sayeem Been Zaman·Arefin Ittesafun Abian·Mohaimenul Azam Khan Raiaan·Saddam Mukta·Md Rafi Ur Rashid·Md Rafiqul Islam·Yakub Sebastian·Sami Azam

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Abstract

Generative artificial intelligence (GenAI) is transforming bioinformatics by advancing genomics, proteomics, transcriptomics, structural biology, and drug discovery. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework, this review addresses six research questions to evaluate influential GenAI strategies in terms of methodological innovation, predictive performance, specialization, limitations, and data use. RQ1 shows that GenAI supports sequence analysis, molecular design, and integrative data modelling, often outperforming traditional methods through improved pattern recognition and generation. RQ2 finds that specialized architectures generally outperform general-purpose models because of domain-specific pretraining and context-aware design. RQ3 identifies benefits in molecular analysis and biological data integration, including improved accuracy and reduced analytical error. RQ4 reports advances in structural modelling, functional prediction, and synthetic data generation, supported by established benchmarks. RQ5 highlights key limitations, including poor scalability, data bias, and restricted generalizability, and recommends stronger evaluation and biologically grounded modelling. RQ6 shows that molecular datasets, including UniProtKB and ProteinNet12, cellular datasets, including CELLxGENE and GTEx, and textual resources, including PubMedQA and OMIM, support model training and generalization. Overall, this review demonstrates the growing potential of GenAI to advance computational biology through more accurate, specialized, and integrative bioinformatics analysis.

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Wasimul Karim, Riasad Alvi, Sayeem Been Zaman, Arefin Ittesafun Abian, Mohaimenul Azam Khan Raiaan, Saddam Mukta, Md Rafi Ur Rashid, Md Rafiqul Islam, Yakub Sebastian, Sami Azam. 2025-11-05. Generative Artificial Intelligence in Bioinformatics: A Systematic Review of Models, Applications, and Methodological Advances. https://doi.org/10.1007/s11831-026-10743-z

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