🖥️ Building a Workstation for Single-Particle Analysis (SPA)

— Two Practical Paths: Research-Grade and Training-Grade Systems

1️⃣ Two Objectives

This series aims to achieve two goals:
(1) Build a research-grade workstation capable of processing full Cryo-EM SPA datasets, and
(2) Provide a training-grade workstation for students or researchers to practice the workflow with limited resources.

TypeResearch WorkstationTraining Workstation
PurposeFull Cryo-EM SPA processingLearning Negative-stain and small Cryo-EM datasets
Budget$8,000–15,000$1,500–3,000
UsersCryo-EM scientists, facility managersStudents, entry-level researchers
Dataset sizeHundreds of GB–TBHundreds of MB–tens of GB

2️⃣ CPU — The Foundation of Parallel Processing

SPA relies heavily on CPU performance for motion correction, CTF estimation, and particle extraction.
Both CryoSPARC and RELION are optimized for Intel’s Math Kernel Library (MKL), making Intel CPUs the most stable and compatible choice.

SystemRecommended SpecsExample CPUsNotes
Research-grade24–32 cores, ≥3.5 GHzIntel XeonExcellent for MPI-based RELION and heavy parallelization
Training-grade8–16 cores, ≥3.0 GHzIntel i9 or i7Strong single-core speed and wide software support

💡 Xeon CPUs support ECC memory and multi-threaded workloads, ideal for large Cryo-EM projects.
i9 CPUs are well-balanced, affordable, and perfect for local learning environments.


3️⃣ GPU — The Core Accelerator

SPA’s 2D/3D classification and refinement steps depend primarily on GPU performance, particularly VRAM capacity.

SystemMinimumRecommendedExample GPUsUse Case
Research-grade16 GB VRAM24–48 GB VRAMNVIDIA RTX A5000 / A6000Large datasets, atomic refinements
Training-grade8 GB VRAM12–16 GB VRAMNVIDIA RTX 4070 / 4070 Ti / RTX 5000Negative-stain and small Cryo-EM datasets

⚠️ If VRAM is insufficient, high-resolution refinements will fail.
A 16 GB GPU is sufficient for most learning and practice datasets.


4️⃣ RAM — The Working Memory

RAM serves as the buffer during massive particle classification or map refinement steps.
Insufficient memory will cause the system to swap to disk and drastically reduce performance.

SystemMinimumRecommendedExample
Research-grade256 GB512 GB (ECC)Xeon-based workstation memory
Training-grade32 GB64 GBStandard DDR5 memory modules

💡 64 GB is sufficient for running both CryoSPARC and RELION with small datasets.
For multi-million particle refinements, 128 GB or higher is strongly recommended.


5️⃣ Storage — Balancing Speed and Capacity

SPA generates massive intermediate files during motion correction, particle extraction, and refinement.
Using a fast NVMe SSD for temporary work and a large-capacity HDD or external SSD for long-term storage provides the best balance.

PurposeResearch SetupTraining Setup
OS + SoftwareNVMe SSD 1 TBNVMe SSD 500 GB
Scratch (Temp)NVMe SSD 2 TBNVMe SSD 1 TB
ArchiveHDD/NAS 10–20 TBExternal SSD 4 TB

💡 CryoSPARC is highly sensitive to scratch disk speed. Always assign a dedicated NVMe drive for temporary files.


6️⃣ Example Configurations

TypeCPUGPURAMStorageTypical Use
Research-gradeXeon(64 cores)RTX A4000 (24 GB) x 4512 GBNVMe 1 TB + Scratch 2 TB + HDD 20 TBFull Cryo-EM SPA pipeline
Training-gradei9 (24 threads)RTX 4070 Ti (12 GB)64 GBNVMe 1 TB + External SSD 4 TBNegative-stain & small Cryo-EM practice

7️⃣ Budget Strategies

Not every lab or student needs a supercomputer.
The goal is to understand the workflow, not necessarily to achieve atomic resolution.

  • Full setup → CryoSPARC + RELION + MotionCor2 + CTFFIND4 on one workstation
  • Limited budget → CryoSPARC standalone + public Negative-stain dataset

💡 The key lesson is experience — learning how data flows through each stage of SPA analysis.


8️⃣ Conclusion

Building your own SPA workstation deepens your understanding of computational and hardware bottlenecks —
how CPU, GPU, RAM, and storage interact during each processing step.
This knowledge helps you design more efficient workflows, even on shared clusters.

The next article will cover Ubuntu setup, CUDA installation, and integrating CryoSPARC and RELION on a single workstation.


Summary

  • Research-grade : Xeon + RTX A4000 x 4 + 512 GB RAM + NVMe 2 TB + HDD 20 TB
  • Training-grade : i9 + RTX 4070 Ti + 64 GB RAM + NVMe 1 TB + External SSD 4 TB
  • Goal : Experience the complete Cryo-EM SPA pipeline in a realistic, reproducible environment