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Chromosome-Level Genome Assembly using the VGP Pipeline

A Galaxy-based bioinformatics project implementing the Vertebrate Genome Project (VGP) workflow to produce a haplotype-phased, chromosome-scale genome assembly from multi-platform sequencing data.


About This Project

Organism: Saccharomyces cerevisiae S288C (Baker's Yeast)
Platform: Galaxy (usegalaxy.org)
Assembly strategy: HiFi + Hi-C + Bionano optical maps (VGP Trajectory D)
Data: Synthetic PacBio HiFi reads simulating a diploid yeast genome

The goal was to reconstruct both haplotypes of a diploid genome from scratch, validate quality at multiple checkpoints, and produce chromosome-level scaffolds — without relying on any reference genome during assembly.


Why These Three Technologies?

Technology What It Contributes
PacBio HiFi Long, accurate reads (10–25 kb, >99% accuracy) for contig assembly
Bionano optical maps Mega-base scale physical information for ordering contigs
Illumina Hi-C 3D chromatin contact data for chromosome-level scaffolding

Each technology addresses a different limitation. HiFi reads span repetitive regions that short reads cannot resolve. Optical maps bridge gaps between distant contigs. Hi-C data anchors scaffolds to chromosome-scale structures.


Pipeline at a Glance

HiFi reads (3 files)
    │
    ▼
Cutadapt ──── Remove adapter-containing reads
    │
    ▼
Meryl + GenomeScope2 ──── K-mer profiling → genome size & heterozygosity
    │
    ▼
Hifiasm (Hi-C mode) ──── Phased contig assembly → Hap1 + Hap2
    │
    ▼
QC checkpoint: gfastats / BUSCO / Merqury
    │
    ▼
Bionano Hybrid Scaffold ──── Optical map integration
    │
    ▼
BWA-MEM2 → YaHS ──── Hi-C scaffolding to chromosome level
    │
    ▼
PretextMap / Pretext Snapshot ──── Final contact map visualisation

Input Data

All datasets are publicly available on Zenodo.

File Format Description
HiFi_synthetic_50x_01–03.fasta FASTA PacBio HiFi reads, 50x coverage
SRR7126301_1.fastq.gz FASTQ.GZ Hi-C forward reads
SRR7126301_2.fastq.gz FASTQ.GZ Hi-C reverse reads
bionano.cmap CMAP Bionano optical map

Download links:


Tools Used

Tool Version Role
Cutadapt 4.4 Adapter removal
Meryl 1.3 K-mer counting
GenomeScope2 2.0 Genome size estimation
Hifiasm 0.19.8 De novo phased assembly
gfastats 1.3.6 Assembly statistics
BUSCO 5.5.0 Gene completeness
Merqury 1.3 Quality value assessment
Bionano Hybrid Scaffold 3.7.0 Optical map scaffolding
BWA-MEM2 2.2.1 Hi-C alignment
YaHS 1.2a.2 Chromosome scaffolding
PretextMap + Snapshot 0.1.9 / 0.0.3 Contact map generation

Key Results

Genome profile (GenomeScope2)

  • Estimated haploid size: ~11.7 Mb
  • Heterozygosity: 0.576%
  • Coverage: ~50x diploid (~25x per haplotype)

Contig assembly (Hifiasm)

  • Hap1: 16 contigs, ~11.3 Mb total
  • Hap2: 17 contigs, ~12.2 Mb total

Final assembly

  • 16 chromosome-level scaffolds (matches the expected yeast karyotype)
  • High BUSCO completeness scores for both haplotypes
  • Hi-C contact maps show clean diagonal banding consistent with correct chromosome assignment

Repository Structure

.
├── README.md
├── workflow/
│   └── VGP_assembly.ga          ← Importable Galaxy workflow
├── results/
│   ├── genomescope/             ← K-mer plots and summary files
│   ├── busco/                   ← BUSCO bar charts (hap1 and hap2)
│   ├── merqury/                 ← Spectra-CN and spectra-ASM plots
│   ├── gfastats/                ← Assembly statistics table
│   └── pretext/                 ← Hi-C contact maps (before/after YaHS)
└── docs/
    └── methods.md               ← Detailed step-by-step methods

How to Run

Requirements: A Galaxy account at usegalaxy.org or usegalaxy.eu with sufficient storage quota.

  1. Import the workflow — Go to Workflow → Import and upload workflow/VGP_assembly.ga

  2. Upload input data — Add all six input files to your Galaxy history. Create a collection from the three HiFi FASTA files named HiFi data. Rename the Hi-C files to Hi-C_dataset_F and Hi-C_dataset_R.

  3. Run — Go to Workflow → Run, select your inputs, and click Run Workflow.

For a full step-by-step walkthrough, follow the official Galaxy Training Network tutorial: https://gxy.io/GTN:T00039


Glossary

Contig — A gapless sequence assembled directly from reads.
Scaffold — Contigs joined together with gap sequences (Ns).
N50 — The contig length at which 50% of the total assembly is covered.
Phasing — Separating reads/contigs into their correct haplotype of origin.
BUSCO — A benchmark measuring how many expected single-copy genes are present and complete.
Hi-C — A sequencing method that captures physical contacts between genomic regions in the nucleus.


References

  • Rhie et al. (2021). Nature, 592, 737–746.
  • Cheng et al. (2021). Nature Methods, 18, 170–175.
  • Zhou et al. (2022). Bioinformatics, 39(1).
  • Ranallo-Benavidez et al. (2020). Nature Communications, 11, 1432.
  • Rhie et al. (2020). Genome Biology, 21, 245.
  • Simão et al. (2015). Bioinformatics, 31(19), 3210–3212.

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