A Workflow-Oriented Framework for Asynchronous Human-AI Collaboration in Hybrid and Compute-Intensive HPC Environments

High-performance computing (HPC) clusters remain the backbone of large-scale scientific computation, traditionally executing deterministic, linear pipelines optimised for predictable performance. However, the pervasive integration of artificial intelligence (AI) and foundation models into scientific research has introduced a fundamentally new computational paradigm. AI-driven workflows are characteristically iterative, data-driven, and probabilistic, introducing unique challenges regarding data gravity, heterogeneous resource management, and complex workflow orchestration. This guide provides twelve practical tips designed to help researchers design efficient, scalable, and reproducible AI-driven HPC workflows. By addressing critical system-level bottlenecks - such as containerisation for environment portability, strategic deployment of job arrays, explicit feedback loop mechanics, and I/O optimisation for small files - this article offers a framework for transitioning from rigid execution pipelines to adaptive, intelligent computational environments. While these architectural principles are broadly applicable across distributed environments, they are particularly tailored to the resource-intensive throughput demands of modern computational biology.

Hyperion is an innovative high-performance computing (HPC) cluster developed for researchers in both science and humanities disciplines at the University of South Carolina (USC). Our approach involved constructing a HPC cluster designed to meet the current research needs while accommodating future expansion. Additionally, we developed and trained two machine learning (ML) models to predict turnaround time, including wait time and wall time, and seamlessly integrated them into the Slurm job submission. Finally, we showcase a variety of sample applications hosted on the Hyperion platform.

Modern scientific research increasingly depends on High-Performance Computing (HPC) infrastructures, yet many researchers face significant operational barriers when interacting with cluster environments, job schedulers, GPU resources, and parallel computing frameworks. General-purpose large language models (LLMs) provide useful coding assistance but often lack the domain-specific operational knowledge required for reliable HPC support. This paper presents HPC-LLM, a retrieval augmented and domain-adapted assistant designed to support common HPC workflows including Slurm scheduling, MPI execution, GPU utilization, filesystem management, and cluster troubleshooting. The proposed framework integrates automated documentation ingestion, dense retrieval, lightweight domain adaptation using QLoRA, and local inference within a modular orchestration pipeline. To support domain adaptation, we construct an HPC-oriented corpus from publicly available university HPC documentation, curated operational examples, and synthetic instruction-answer pairs generated from retrieved HPC content. The resulting dataset contains approximately 9,000 to 24,000 HPC-focused training examples spanning job scheduling, GPU computing, distributed training, storage systems, and cluster administration topics. We fine-tune Llama 3.1 8B using QLoRA and evaluate the resulting model against several open weight baselines under retrieval-augmented settings on JetStream2 infrastructure. Experimental results indicate that the adapted 8B model achieves performance comparable to substantially larger general-purpose models while operating under significantly lower GPU memory requirements and inference latency. In particular, the adapted model approaches the performance of Qwen 2.5 14B while requiring substantially fewer computational resources.