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dSHERLOCK

This repository holds the code to analyze dSHERLOCK reactions.

Code

Explanation of modules in Analysis:

Module Use Input data format Output data format
Image extracting fluorescence over time for each partition from image files .tif (two-channel image series) .csv (timeseries of intensity for each partition)
Timeseries extracting features from fluorescence over time .csv (timeseries of intensity for each partition) .csv (features extracted after selected pseudo-end-timepoint)
Auxiliary helper functions N.A. N.A.

Modules in Figures contain helper functions for plotting.

Explanation of Jupyter notebooks:

Notebook Use
Image_processing_Example_data.ipynb applying the Image and Timeseries pipelines to the example image file, giving timeseries and features as results
Thresholding_Example_data.ipynb determining fraction of positive compartments through thresholding (most commonly maximum intensity feat_fq_delta_max) for simple positive vs. negative
Classification_Example_data.ipynb applying a pre-trained classifier for allele fraction quantification
Classification.ipynb training a classifier and subsequently using the classifier for allele fraction quantification. NOTE: using this notebook needs the full training dataset and the full admix dataset which are both very large and its presence is intended more as a read-only reference to understand the training pipeline

Pipeline explanation: First, the Image and Timeseries scripts need to be applied to newly recorded data. See jupyter notebook Image_processing_Example_data.ipynb for an example. Subsequently, there are two options:

  • thresholding on one extracted feature (most commonly maximum intensity feat_fq_delta_max) for simple positive vs. negative. See jupyter notebook Thresholding_Example_data.ipynb for an example.
  • classification with pre-trained classifier for allele fraction quantification. See jupyter notebook Classification_Example_data.ipynb for an example.

Data

Example data can be downloaded from figshare with the following DOI: 10.6084/m9.figshare.29944823

It contains some example data folders selected to illustrate each part of the pipeline using the jupyter notebooks.

Model

The model directory contains checkpoints of the trained model for FKS1 SNP quantification.

Environment

The environment.yml file contains the necessary packages. For improved reproducibility this entire repository is also available as a containerized code ocean code capsule with the title "Digital CRISPR-based diagnostics for quantification of Candida auris and resistance mutations".

Contributing

If you would like to contribute, please reach out to Anton Thieme anton@thiemenet.de.

License

MIT

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