How I Built a DNA Mutation Predictor Using ESM-2 and XGBoost (Open Source) As a Highskewler :]

I built a tool that tells you if a DNA mutation causes disease. No cloud API. No paid service. Just a Python CLI on your laptop.

Here's how it works — and how you can run it yourself.

The Problem
hen a single nucleotide changes in DNA (a missense mutation), it can alter a protein's function. Some changes cause disease. Most don't. ClinVar — the NIH's database of known variants — has ~2,800 classified missense mutations. I wanted to build a classifier that could predict pathogenicity from sequence alone.

The Stack

• ESM-2 (facebook/esm2_t30_150M_UR50D) — a 150M-parameter protein language model from Meta. It reads protein sequences and produces 640-dimensional embeddings that capture evolutionary and structural information.
• XGBoost — gradient boosted trees, trained on 40 selected features from the ESM-2 embed-dings.
• scikit-learn — feature selection (SelectKBest) and scaling (StandardScaler).

No deep learning at inference time. The ESM-2 embeddings are computed once and fed into a lightweight XGBoost model. The result: 82.5% accuracy on a 2,792-sample ClinVar dataset.

How It Works

1. You input a protein symbol + mutation (e.g., BRCA1 A1708E)
2. The tool fetches the protein sequence from UniProt
3. ESM-2 produces a 640-dim embedding for the mutated sequence
4. XGBoost classifies: PATHOGENIC or BENIGN
5. You get a confidence score + a protein feature graph

Running It

git clone https://github.com/NOOBHEKER/dna-mutation-predictor.git
cd dna-mutation-predictor
pip install -r requirements.txt
python -m src.cli

Or double-click predict.bat on Windows — it sets up everything automatically.

What I Learned

• ESM-2 embeddings contain enough signal to classify pathogenicity without hand-crafted features
• Feature selection matters: 40 out of 640 dimensions outperformed the full embedding
• CPU inference is slow (~30s per prediction) but acceptable for research use
• The hardest part was cleaning ClinVar data, not training the model

Try It
The project is open source under MIT license. Clone it, break it, improve it.

GitHub: https://github.com/NOOBHEKER/dna-mutation-predictor
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If it's useful to your research, I'd appreciate a star or a coffee.