LC-MS/MS Spectrum Prediction

Goal

Predict the LC-MS/MS (tandem mass) spectrum of a molecule given its SMILES string using ICEBERG — a two-stage GNN that first generates a fragmentation DAG (fragment ions) and then predicts their intensities. Output is a predicted spectrum (m/z, intensity) with optional fragment SMILES assignments per peak.

When to Use This Skill

• A SMILES string is known and a predicted LC-MS/MS spectrum (m/z vs intensity) is needed.
• Fragment ion assignments (SMILES per peak) are required.
• No reference spectrum exists, or comparison to a predicted spectrum is desired.
• Companion skill chem-spectrum-matcher can compare predicted vs experimental spectra.

When NOT to Use This Skill

• Experimental spectrum already available — use it directly; no prediction needed.
• Only compound name known — first resolve to SMILES via drug-db-pubchem, then call this skill.
• GC-MS or other MS types — ICEBERG is trained on LC-MS/MS only; flag a warning before proceeding.
• Organometallics or MW > 1000 — predictions may be unreliable or fail due to unsupported element types.

Prerequisites

1. Download ICEBERG checkpoints

Download from coleygroup/ms-pred releases and place in downloads/:

downloads/
├── iceberg_dag_gen_msg_best.ckpt     # generator (stage 1)
└── iceberg_dag_inten_msg_best.ckpt   # intensity predictor (stage 2)

Flag error and stop if either checkpoint is missing.

2. Set up the conda environment

bash conda-envs/msms-agent/install.sh

The ms_pred Python package is installed from GitHub automatically by the install script.

Instructions

Step 1 — Run inference and generate spectrum

# Env: ms-gen
python .agents/skills/chem-msms-predict/scripts/predict_msms.py \
    --smiles "c1ccccc1C(=O)OCCN" \
    --gen_ckpt downloads/iceberg_dag_gen_msg_best.ckpt \
    --inten_ckpt downloads/iceberg_dag_inten_msg_best.ckpt \
    --collision_energies 20 40 \
    --adduct "[M+H]+" \
    --instrument "Orbitrap" \
    --output_dir results/msms_prediction

Key parameters:

• --smiles — input molecule as SMILES string
• --gen_ckpt / --inten_ckpt — paths to ICEBERG checkpoints
• --collision_energies — one or more collision energies in eV (e.g. 20 40 60); model was trained on absolute eV values
• --adduct — supported adducts: [M+H]+, [M-H]-, [M+Na]+, [M+NH4]+, and others from ms_pred.common.ion2mass
• --instrument — instrument type for intensity prediction (e.g. "Orbitrap", "QTOF")
• --threshold — confidence cutoff for DAG fragment generator (default 0.1; lower = more fragments)
• --sparse_k — maximum number of peaks returned (default 100)
• --cuda_devices — GPU device IDs (e.g. "0" or "0,1"); omit or set to None for CPU

Outputs written to --output_dir: | File | Description | |------|-------------| | spectrum.png | Stem plot of predicted spectrum, one panel per collision energy | | fragments.json | JSON list per CE: {mz, intensity, fragment_smiles} sorted by intensity | | input_configs.yaml | All run parameters for reproducibility |

Step 2 — Inspect fragment assignments (optional)

fragments.json maps each predicted peak to the fragment ion SMILES responsible for it:

{
  "20": [
    {"mz": 122.0600, "intensity": 1.0, "fragment_smiles": "c1ccccc1C=O"},
    ...
  ]
}

Use this to rationalize which bonds fragment at which energy.

Step 3 — Compare with experimental spectrum (optional)

If an experimental spectrum is available, use the companion skill:

→ chem-spectrum-matcher

Examples

2-Aminoethyl benzoate (c1ccccc1C(=O)OCCN)

# Env: ms-gen
python .agents/skills/chem-msms-predict/examples/predict_smiles.py \
    --gen_ckpt downloads/iceberg_dag_gen_msg_best.ckpt \
    --inten_ckpt downloads/iceberg_dag_inten_msg_best.ckpt \
    --output_dir .agents/test/msms_example

Expected output:

• spectrum.png — two-panel spectrum (20 eV + 40 eV)
• fragments.json — fragment assignments for both energies
• Precursor [M+H]+ ≈ 166.087 Da

Constraints

• Environment: All scripts require the ms-gen conda environment. ms_pred is installed automatically from GitHub by conda-envs/msms-agent/install.sh.
• Checkpoints required: Script raises FileNotFoundError if --gen_ckpt or --inten_ckpt are missing.
• Collision energy units: Use absolute eV values. To convert NCE → eV, set nce=True in iceberg_prediction() directly.
• Non-binned output only: This skill uses binned_out=False (high-precision m/z). Binned output disables fragment assignment.
• Single-compound inference: Provide one SMILES per call. For batch prediction, loop over SMILES and use separate output dirs.
• Unsupported elements: Molecules containing metals, lanthanides, or rare main-group elements may fail or produce low-quality predictions.
• MW limit: ICEBERG is unreliable for MW > 1000 Da.

References

• Alberts, M. et al., "Artificial intelligence for context-aware mass spectrometry", Nature Methods, 2025. DOI:10.1038/s41592-025-02658-z
• ICEBERG source code: github.com/coleygroup/ms-pred

---

Author: Magdalena Lederbauer Contact: GitHub @mlederbauer