High-throughput biological data generation has driven the adoption of automated bioinformatics pipelines on high-performance computing (HPC) systems and supercomputers. This systematic review synthesizes 101 studies published between 2018 and 2025, following PRISMA guidelines, to examine workflow management systems (WfMSs) deployed in HPC environments across genomics, transcriptomics, proteomics, and metagenomics domains. We analyzed prominent frameworks including Nextflow, Snakemake, WDL, and CWL, documenting their implementation challenges and emerging solutions. Key challenges identified include scheduler saturation from massive parallelism, I/O bottlenecks on shared file systems, heterogeneous resource allocation, and reproducibility across diverse computing environments. Containerization through Docker and Singularity has emerged as the dominant solution for ensuring portability and reproducibility. Community-driven initiatives like nf-core have accelerated adoption by providing curated, best-practice pipelines. Advanced solutions include HPC-aware scheduling strategies, hybrid cloud-HPC architectures, and GPU integration for machine learning-augmented analyses. While significant progress has been made in automating complex multi-step analyses, continued co-evolution of workflow systems and HPC infrastructure remains essential for handling exascale data volumes and achieving fully reproducible computational biology at scale.

ASHIMGALIYEV M.

PhD, lecturer, department of computer and software engineering, faculty information technologies, L.N. Gumilyov Eurasian national university, Astana, Kazakhstan.

E-mail: ashimgaliyev.medet@gmail.com, https://orcid.org/0009-0003-9829-6187

MUSSABEK M.

Senior lecturer, school of artificial intelligence and data science, Astana IT University, Astana, Kazakhstan

E-mail: miras.k@astanait.edu.kz, https://orcid.org/0009-0009-2353-3524

MATKARIMOV B.

Doctor of technical sciences, professor, lecturer and researcher, department of artificial intelligence technology, faculty information technologies, L.N. Gumilyov Eurasian national university, Astana, Kazakhstan

E-mail: bakhyt.matkarimov@gmail.com, https://orcid.org/0000-0003-0775-7324

ZHUMADILLAYEVA A.K.

Candidate of technical sciences, associate professor, department of computer and software engineering, faculty information technologies, L.N. Gumilyov Eurasian national university, Astana, Kazakhstan.

E-mail: Ainur.Zhumadillayeva@astanait.edu.kz, https://orcid.org/0000-0003-1042-0415

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bioinformatics pipelines, containerization, high-performance computing, reproducibility, scalability, workflow management systems