Metadata-Version: 2.1
Name: deepac
Version: 0.13.1
Summary: Predicting pathogenic potentials of novel DNA with reverse-complement neural networks.
Home-page: https://gitlab.com/rki_bioinformatics/DeePaC
Author: Jakub Bartoszewicz
Author-email: jakub.bartoszewicz@hpi.de
License: MIT
Keywords: deep learning DNA sequencing synthetic biology pathogenicity prediction
Platform: UNKNOWN
Classifier: Development Status :: 4 - Beta
Classifier: License :: OSI Approved :: MIT License
Classifier: Programming Language :: Python :: 3
Classifier: Programming Language :: Python :: 3.6
Classifier: Programming Language :: Python :: 3.7
Classifier: Programming Language :: Python :: 3.8
Classifier: Topic :: Scientific/Engineering :: Bio-Informatics
Requires-Python: >=3
Description-Content-Type: text/markdown
Requires-Dist: tensorflow (>=2.1.2)
Requires-Dist: biopython (>=1.78)
Requires-Dist: scikit-learn (>=0.22.1)
Requires-Dist: matplotlib (>=3.1.3)
Requires-Dist: numpy (>=1.17)
Requires-Dist: h5py (>=2.10)
Requires-Dist: psutil (>=5.6.7)
Requires-Dist: pandas (>=1.0.3)
Requires-Dist: shap (>=0.35)
Requires-Dist: weblogo (>=3.7)
Requires-Dist: pybedtools (>=0.8.1)
Requires-Dist: statsmodels (>=0.11.0)
Requires-Dist: seaborn (>=0.11)
Requires-Dist: tqdm (>=4.49)

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# DeePaC

DeePaC is a python package and a CLI tool for predicting labels (e.g. pathogenic potentials) from short DNA sequences (e.g. Illumina 
reads) with interpretable reverse-complement neural networks. For details, see our preprint on bioRxiv: 
<https://www.biorxiv.org/content/10.1101/535286v3> and the paper in *Bioinformatics*: <https://doi.org/10.1093/bioinformatics/btz541>.
For details regarding the interpretability functionalities of DeePaC, see the preprint here: <https://www.biorxiv.org/content/10.1101/2020.01.29.925354v2>

Documentation can be found here:
<https://rki_bioinformatics.gitlab.io/DeePaC/>. 
See also the main repo here: <https://gitlab.com/rki_bioinformatics/DeePaC>.

## Plug-ins
### DeePaC-strain
Basic version of DeePaC comes with built-in models trained to predict pathogenic potentials of NGS reads originating from
novel *bacteral species*. If you want to predict pathogenicity of novel *strains* of *known* species, try the DeePaC-strain plugin available here:
<https://gitlab.com/dacs-hpi/DeePaC-strain>. 

### DeePaC-vir
If you want to detect novel human viruses, try the DeePaC-vir plugin: <https://gitlab.com/dacs-hpi/DeePaC-vir>. 

### DeePaC-Live
If you want to run the predictions in real-time during an Illumina sequencing run, try DeePaC-Live: <https://gitlab.com/dacs-hpi/deepac-live>. 


## Installation

### Recommended: set up an environment

We recomment setting up an isolated `conda` environment:
```
conda create -n my_env
conda activate my_env
```

or, alternatively, a `virtualenv`:
```
virtualenv --system-site-packages my_env
source my_env/bin/activate
```


### With conda (recommended)
 [![install with bioconda](https://img.shields.io/badge/install%20with-bioconda-brightgreen.svg?style=flat)](http://bioconda.github.io/recipes/deepac/README.html)

You can install DeePaC with `bioconda`. Set up the [bioconda channel](
<https://bioconda.github.io/user/install.html#set-up-channels>) first, and then:
```
conda install deepac
```

Note: the latest version of deepac is not available on bioconda. If you use the builtin models only, the older version 
should be perfectly fine. If you want to use more advanced functionalities (custom models, interpretability suite etc.), install deepac with `pip`. You can conveniently install all the dependencies via conda:

```
conda install tensorflow-gpu # For GPU support; see below
conda install deepac --only-deps
conda install seaborn
pip install deepac --no-deps
```


If you want to install the plugins as well, use:

```
conda install deepacvir deepacstrain
```

### With pip

You can also install DeePaC with `pip`:
```
pip install deepac
```

If you want to install the plugins, use:

```
pip install deepacvir deepacstrain
```

### GPU support

To use GPUs, you need to install the GPU version of TensorFlow. In conda, install tensorflow-gpu before deepac:
```
conda remove tensorflow
conda install tensorflow-gpu
conda install deepac
```

If you're using `pip`, you need to install CUDA and CuDNN first (see TensorFlow installation guide for details). Then
you can do the same as above:
```
pip uninstall tensorflow
pip install tensorflow-gpu
```

### Optional: run tests
Optionally, you can run explicit tests of your installation. Note that it may take some time on a CPU.
```
# Run standard tests
deepac test
# Run quick tests (eg. on CPUs)
deepac test -q
# Test using specific GPUs (here: /device:GPU:0 and /device:GPU:1) 
deepac test -g 0 1
# Test explainability and gwpa workflows
deepac test -xp
# Full tests
deepac test -a
# Full quick tests (eg. on GPUs with limited memory)
deepac test -aq
```

### Help

To see help, just use
```
deepac --help
deepac predict --help
deepac train --help
# Etc.
```

## Basic use: prediction

You can predict pathogenic potentials with one of the built-in models out of the box:
```
# A rapid CNN (trained on IMG/M data)
deepac predict -r input.fasta
# A sensitive LSTM (trained on IMG/M data)
deepac predict -s input.fasta
```

The rapid and the sensitive models are trained to predict pathogenic potentials of novel bacterial species.
For details, see <https://doi.org/10.1093/bioinformatics/btz541> or <https://www.biorxiv.org/content/10.1101/535286v3>.

To quickly filter your data according to predicted pathogenic potentials, you can use:
```
deepac predict -r input.fasta
deepac filter input.fasta input_predictions.npy -t 0.5
```
Note that after running `predict`, you can use the `input_predictions.npy` to filter your fasta file with different
thresholds. You can also add pathogenic potentials to the fasta headers in the output files:
```
deepac filter input.fasta input_predictions.npy -t 0.75 -p -o output-75.fasta
deepac filter input.fasta input_predictions.npy -t 0.9 -p -o output-90.fasta
```

## Advanced use
### Config templates
To get the config templates in the current working directory, simply use:
```
deepac templates
```
### Preprocessing

For more complex analyzes, it can be useful to preprocess the fasta files by converting them to binary numpy arrays. Use:
```
deepac preproc preproc_config.ini
```
See the `config_templates` directory of the GitLab repository (https://gitlab.com/rki_bioinformatics/DeePaC/) for a sample configuration file.

### Training
You can use the built-in architectures to train a new model:
```
deepac train -r -T train_data.npy -t train_labels.npy -V val_data.npy -v val_labels.npy
deepac train -s -T train_data.npy -t train_labels.npy -V val_data.npy -v val_labels.npy

```

To train a new model based on you custom configuration, use
```
deepac train -c nn_train_config.ini
```

If you train an LSTM on a GPU, a CUDNNLSTM implementation will be used. To convert the resulting model to be 
CPU-compatible, use `deepac convert`. You can also use it to save the weights of a model, or recompile a model 
from a set of weights:

```
# Save model weights and convert the model to an equivalent with the same architecture and weights.
# Other config parameters can be adjusted
deepac convert model_config.ini saved_model.h5
# Recompile the model
deepac convert saved_model_config.ini saved_model_weights.h5 -w
```

### Evaluation

To evaluate a trained model, use
```
# Read-by-read performance
deepac eval -r eval_config.ini
# Species-by-species performance
deepac eval -s eval_species_config.ini
# Ensemble performance
deepac eval -e eval_ens_config.ini
```
See the configs directory for sample configuration files. Note that `deepac eval -s` requires precomputed predictions 
and a csv file with a number of DNA reads for each species in each of the classes.

### TPU (experimental)
If you want to use a TPU, run DeePaC with the `--tpu` parameter:
```
# Test a TPU
deepac --tpu colab test
```

## Intepretability workflows
### Filter visualization
To find the most relevant filters and visualize them, use the following minimum workflow: 
```
# Calculate filter and nucleotide contibutions (partial Shapley values) for the first convolutional layer
# using mean-centered weight matrices and "easy" calculation mode
deepac explain fcontribs -m model.h5 -eb -t test_data.npy -N test_nonpatho.fasta -P test_patho.fasta -o fcontribs 

# Create filter ranking
deepac explain franking -f fcontribs/filter_scores -y test_labels.npy -p test_predictions.npy -o franking

# Prepare transfac files for filter visualization (weighted by filter contribution)
deepac explain fa2transfac -i fcontribs/fasta -o fcontribs/transfac -w -W fcontribs/filter_scores

# Visualize nucleotide contribution sequence logos
deepac explain xlogos -i fcontribs/fasta -s fcontribs/nuc_scores -I fcontribs/transfac -t train_data.npy -o xlogos
```
You can browse through other supplementary functionalities and parameters by checking the help:
```
deepac explain -h
deepac explain fcontribs -h
deepac explain xlogos -h
# etc.
```

### Genome-wide phenotype potential analysis (GWPA)
To find interesting regions of a whole genome, use this workflow to generate nucleotide-resolution maps of
predicted phenotype potentials and nucleotide contributions:
```
# Fragment the genomes into pseudoreads
deepac gwpa fragment -g genomes_fasta -o fragmented_genomes

# Predict the pathogenic potential of each pseudoread
deepac predict -r -a fragmented_genomes/sample1_fragmented_genomes.npy -o predictions/sample1_pred.npy

# Create bedgraphs of mean pathogenic potential at each position of the genome
# Can be visualized in IGV
deepac gwpa genomemap -f fragmented_genomes -p predictions -g genomes_genome -o bedgraph

# Rank genes by mean pathogenic potential
deepac gwpa granking -p bedgraph -g genomes_gff -o granking

# Create bedgraphs of mean nuclotide contribution at each position of the genome
# Can be visualized in IGV
deepac gwpa ntcontribs -m model.h5 -f fragmented_genomes -g genomes_genome -o bedgraph_nt
```
You can browse through other supplementary functionalities and parameters by checking the help:
```
deepac gwpa -h
deepac gwpa genomemap -h
deepac gwpa ntcontribs -h
# etc.
```
### Filter enrichment analysis
Finally, you can check for filter enrichment in annotated genes or other genomic features:
```
# Get filter activations, genome-wide
deepac gwpa factiv -m model.h5 -t fragmented_genomes/sample1_fragmented_genomes.npy -f fragmented_genomes/sample1_fragmented_genomes.fasta -o factiv

# Check for enrichment within annotated genomic features
deepac gwpa fenrichment -i factiv -g genomes_gff/sample1.gff -o fenrichment
```
## Supplementary data and scripts
Datasets are available here: <https://doi.org/10.5281/zenodo.3678562> (bacteria) and here: <https://doi.org/10.5281/zenodo.3630803> (viruses).
In the supplement_paper directory you can find the R scripts and data files used in the papers for dataset preprocessing and benchmarking.

## Cite us
If you find DeePaC useful, please cite:

```
@article{10.1093/bioinformatics/btz541,
    author = {Bartoszewicz, Jakub M and Seidel, Anja and Rentzsch, Robert and Renard, Bernhard Y},
    title = "{DeePaC: predicting pathogenic potential of novel DNA with reverse-complement neural networks}",
    journal = {Bioinformatics},
    year = {2019},
    month = {07},
    issn = {1367-4803},
    doi = {10.1093/bioinformatics/btz541},
    url = {https://doi.org/10.1093/bioinformatics/btz541},
    eprint = {http://oup.prod.sis.lan/bioinformatics/advance-article-pdf/doi/10.1093/bioinformatics/btz541/28971344/btz541.pdf},
}

@article {Bartoszewicz2020.01.29.925354,
    author = {Bartoszewicz, Jakub M. and Seidel, Anja and Renard, Bernhard Y.},
    title = {Interpretable detection of novel human viruses from genome sequencing data},
    elocation-id = {2020.01.29.925354},
    year = {2020},
    doi = {10.1101/2020.01.29.925354},
    publisher = {Cold Spring Harbor Laboratory},
    URL = {https://www.biorxiv.org/content/early/2020/02/01/2020.01.29.925354},
    eprint = {https://www.biorxiv.org/content/early/2020/02/01/2020.01.29.925354.full.pdf},
    journal = {bioRxiv}
}

```

