ML-maternal-cell-contamination

This repository contains accompanying code for the paper Accurate Fetal Variant Calling in the Presence of Maternal Cell Contamination. It consists of three parts:

1. Utilities for:

   • Working with VCF files
   • Using a pretrained model to recalibrate the genotype (GATK output) of a contaminated sample
   • Training your own model on synthetic data

2. Notebooks to reproduce our results from the corresponding paper, as well as an example notebook with a demonstration of the usage of our scripts. See notebooks/example.ipynb.

3. A CLI script for genotype recalibration. See python/main.py.

Dataset

The dataset containing simulated contaminated samples trios and corresponding "pure child" samples is available here (direct download link). For training, place the data directory into the root of the repository.

Usage

usage: main.py [-h] [-v] [-r] [-c] [--model_path MODEL_PATH]
               [--method {xgboost,logistic-regression,confidence-intervals,meta-classifier}]
               [--contamination CONTAMINATION] [--output OUTPUT]
               [--GQ_sa GQ_SA] [--GQ_mo GQ_MO] [--GQ_fa GQ_FA] [--DP_sa DP_SA]
               [--DP_mo DP_MO] [--DP_fa DP_FA] [--mode {micro,macro}]
               path sample_name mother_name father_name

positional arguments:
  path                  path to input VCF file
  sample_name           name of sample column in VCF file
  mother_name           name of mother column in VCF file
  father_name           name of father column in VCF file

optional arguments:
  -h, --help            show this help message and exit
  -v, --verbose         enable verbose output
  -r, --recalibrate     recalibrate a VCF file
  -c, --estimate_contamination
                        estimate and output the fraction of maternal cell contamination
                        given a VCF file
  --model_path MODEL_PATH
                        path to saved recalibrator model
  --method {xgboost,logistic-regression,confidence-intervals,meta-classifier}
                        recalibration method
  --contamination CONTAMINATION
                        user provided contamination estimate (calculated otherwise)
  --output OUTPUT       path to output VCF file
  --GQ_sa GQ_SA         Genotype quality cutoff to use when estimating
                        contamination (sample column)
  --GQ_mo GQ_MO         Genotype quality cutoff to use when estimating
                        contamination (mother column)
  --GQ_fa GQ_FA         Genotype quality cutoff to use when estimating
                        contamination (father column)
  --DP_sa DP_SA         Read depth cutoff to use when estimating contamination
                        (sample column)
  --DP_mo DP_MO         Read depth cutoff to use when estimating contamination
                        (mother column)
  --DP_fa DP_FA         Read depth cutoff to use when estimating contamination
                        (father column)
  --mode {micro,macro}  Averaging mode for contamination estimation