Gene GEM Correlation Analysis (GGCA)

Computes efficiently the correlation (Pearson, Spearman or Kendall) and the p-value (two-sided) between all the pairs from two datasets. It also supports CpG Site IDs.

IMPORTANT: GGCA is the heart of a platform called Multiomix. On the official website you will be able to use this library in a fast and agile way through a friendly graphical interface (along with many extra features!). Go to https://multiomix.org/ to get started now!

Python PyPi | Rust Crate

Index

• Requirements
• Usage
  • Python
  • Rust
• Contributing
• Considerations

Requirements

You need to install GSL >= 2.6 in your system to use this library.

Usage

There are a few examples in examples folder for both languages.

Python

1. Install: pip install ggca
2. Configure and call the correlate method:

```python import ggca

Possible Correlation methods

SPEARMAN = 1 KENDALL = 2 PEARSON = 3

Possible P-values adjustment methods

BENJAMINIHOCHBERG = 1 BENJAMINIYEKUTIELI = 2 BONFERRONI = 3

mrnafilepath = "mrna.csv" gemfilepath = "mirna.csv"

try: (resultcombinations, evaluatedcombinations) = ggca.correlate( mrnafilepath, gemfilepath, correlationmethod=PEARSON, correlationthreshold=0.5, sortbufsize=2000000, adjustmentmethod=BENJAMINIHOCHBERG, allvsall=True, gemcontainscpg=False, collectgemdataset=None, keeptopn=2 # Keeps only top 2 elements )

print(f'Number of resulting combinations: {len(result_combinations)} of {evaluated_combinations} evaluated combinations')
for combination in result_combinations:
    print(
        combination.gene,
        combination.gem,
        combination.correlation,
        combination.p_value,
        combination.adjusted_p_value
    )

except ggca.GGCADiffSamplesLength as ex: print('Raised GGCADiffSamplesLength:', ex) except ggca.GGCADiffSamples as ex: print('Raised GGCADiffSamples:', ex) except ggca.InvalidCorrelationMethod as ex: print('Raised InvalidCorrelationMethod:', ex) except ggca.InvalidAdjustmentMethod as ex: print('Raised InvalidAdjustmentMethod:', ex) except ggca.GGCAError as ex: print('Raised GGCAError:', ex) ```

Rust

1. Add crate to Cargo.toml: ggca = "0.4.0"
2. Create an analysis and run it:

```rust use ggca::adjustment::AdjustmentMethod; use ggca::analysis::Analysis; use ggca::correlation::CorrelationMethod;

// File's paths let df1path = "mrna.csv"; let df2path = "mirna.csv";

// Some parameters let gemcontainscpg = false; let isallvsall = true; let keeptopn = Some(10); // Keeps the top 10 of correlation (sorting by abs values) let collectgem_dataset = None; // Better performance. Keep small GEM files in memory

let analysis = Analysis::newfromfiles(df1path.tostring(), df2path.tostring(), false); let (result, numberofelementsevaluated) = analysis.compute( CorrelationMethod::Pearson, 0.7, 2000000, AdjustmentMethod::BenjaminiHochberg, isallvsall, collectgemdataset, keeptopn, )?;

println!("Number of elements -> {} of {} combinations evaluated", result.len(), numberofelements_evaluated);

for corpvalue in result.iter() { println!("{}", corpvalue); } ```

Note that envlogger crate is used to provide some warning in case some mRNA/GEM combinations produce NaN values (for instance, because the input array has 0 std). In that case, you can add RUSTLOG=warn to your command to produce warnings in the stderr. E.g:

RUST_LOG=warn cargo test --no-default-features --tests

or

RUST_LOG=warn cargo run --example basic --no-default-features

Contributing

All kind of help is welcome! Feel free o submit an issue or a PR. There are some TODOs which are listed below:

• [ ] Parallelize iterators to improve performance
• [ ] Make Rust enums accessible from Python
• [ ] Add support for Windows OS
• [X] Add Rust documentation
• [X] Add tests
• [X] Add MyPy support

Developing

We provide a Docker image to execute all the commands listed below:

• Build for rust: cargo build [--release]
• Build for Python (uses Maturin):
  1. First of all, remove the target/wheels folder: rm -rf ./target/wheels
  2. Build wheels: docker run --rm -v $(pwd):/io jwaresolutions/ggca-build:0.2.3 maturin build --release --skip-auditwheel --manylinux=2014
  3. Repair wheels to include some missing .so files: docker run --rm -v $(pwd):/io jwaresolutions/ggca-build:0.2.3 ./repair-wheels.sh
• Only for development:
  • To run the examples you must run with this command due to an issue with Pyo3: cargo run [--release] --no-default-features --example <example>
  • In Python you can test with Maturin:
    • Maturin develop (installs the package in your current virtualenv): maturin develop
    • Maturin build (just builds the wheel for your current Python version): maturin build --manylinux=1-unchecked
• To publish in PyPi:
  1. Install twine: pip install twine
  2. Upload: twine upload ./target/wheels/wheelhouse/*

Tests

All the correlation, p-values and adjusted p-values were taken from cor.test and p.adjust functions from the R programming language and statsmodels package for Python language.

Data in small_files folder was retrieved with random sampling from the Colorectal Adenocarcinoma (TCGA, Nature 2012) dataset. This dataset can be downloaded from cBioPortal datasets page or this direct link.

All the correlations results were compared directly with R-Multiomics output (old version of multiomix.org only available for R lang).

Performance

We use criterion.rs to perform benchmarks. In case you have made a contribution you can check that no regression was added to the project. Just run cargo bench --no-default-features before and after your changes to perform a statistical analysis of performance.

Considerations

If you use any part of our code, or the tool itself is useful for your research, please consider citing:

@article{camele2022multiomix, title={Multiomix: a cloud-based platform to infer cancer genomic and epigenomic events associated with gene expression modulation}, author={Camele, Genaro and Menazzi, Sebastian and Chanfreau, Hern{\'a}n and Marraco, Agustin and Hasperu{\'e}, Waldo and Butti, Matias D and Abba, Martin C}, journal={Bioinformatics}, volume={38}, number={3}, pages={866--868}, year={2022}, publisher={Oxford University Press} }