Pipeline Overview

Pipeline Overview

End-to-end workflow

Patient biopsy
    │
    ▼
NGS (Shotgun sequencing)          ← PRJEB71108 cohort (peri-implantitis)
    │  bowtie2 alignment
    ▼
MetaPhlAn 4                       ← relative abundance per genus
    │  metaphlan_feature_table_to_init_comp.py
    ▼
init_comp.json                    ← normalized fractions: Str/Act/Vel/Hae/Rot/Fus/Por
    │
    ├─────────────────────────────────────────┐
    │                                         │
    ▼                                         ▼
AGORA GEM library                     Hamilton ODE (0D)
(~800 reconstructions)                TMCMC-calibrated parameters
    │  select 5 species                       │
    ▼                                         ▼
GEM per species                       Community composition φ(t)
(~1000 rxns / ~800 metabolites)               │
    │                                         ▼
    ▼                                   Dysbiosis Index (DI)
dFBA (LP per species per Δt)
max μ s.t. stoichiometry + medium
    │  medium update t→t+Δt
    ▼
COMETS (Java + cometspy)             ← 2D spatial: 60×40 voxel grid
    │                                  z=0: implant surface
    │                                  z=top: GCF/saliva reservoir
    ▼
Metabolic profile (80 h)
  · species biomass timecourse
  · lactate, succinate, O₂ gradients
  · pH proxy

Key components

Component	Tool	Purpose
Sequencing	Illumina shotgun	Patient metagenome
Profiling	MetaPhlAn 4.2.4	Relative abundance → genus fractions
GEM library	AGORA v1.03	Genome-scale metabolic reconstructions
dFBA solver	COMETS (Java)	LP per species per Δt
2D spatial	cometspy	Nutrient diffusion + growth on grid
Sensitivity	SALib (Sobol)	N=256, 12 kinetic params

Running the pipeline

# Step A — 0D parameter sweep
python comets/run_comets_pipeline.py --step A

# Step B — 2D spatial (healthy vs diseased)
# submitted via PBS:
qsub comets/run_comets_BC.sh

# Step C — patient-specific (requires MetaPhlAn output)
python comets/run_comets_pipeline.py --step C \
    --init-comp data/metaphlan_profiles/init_comp_ERR13166576_A_3.json

Output figures

File	Content
pipeline_results/A_0d_comparison.png	0D healthy vs diseased timecourse
pipeline_results/B_spatial_comparison.png	2D spatial biomass + nutrients
pipeline_results/sobol_sensitivity.png	Sobol sensitivity indices
pipeline_results/pipeline_overview.png	Pipeline diagram