RFMix-reader

RFMix-reader is a Python package designed to efficiently read and process output files generated by RFMix, a popular tool for estimating local ancestry in admixed populations. The package employs a lazy loading approach, which minimizes memory consumption by reading only the loci that are accessed by the user, rather than loading the entire dataset into memory at once. Additionally, we leverage GPU acceleration to improve computational speed.

Install

rfmix-reader can be installed using pip:

bash pip install rfmix-reader

GPU Acceleration: rfmix-reader leverages GPU acceleration for improved performance. To use this functionality, you will need to install the following libraries for your specific CUDA version: - RAPIDS: Refer to official installation guide here - PyTorch: Installation instructions can be found here

Additional Notes: - We have not tested installation with Docker or Conda environemnts. Compatibility may vary. - If you do not have GPU, you can still use the basic functionality of rfmix-reader. This is still much faster than processing the files with stardard scripting.

Key Features

Lazy Loading - Reads data on-the-fly as requested, reducing memory footprint. - Ideal for working with large RFMix output files that may not fit entirely in memory.

Efficient Data Access - Provides convenient access to specific loci or regions of interest. - Allows for selective loading of data, enabling faster processing times.

Seamless Integration - Designed to work seamlessly with existing Python data analysis workflows. - Facilitates downstream analysis and manipulation of RFMix output data.

Loci Imputation - Designed to impute local ancestry loci to a larger genotype data genomic positions. - Array-based data for ease of integration with downstream analysis.

Whether you are working with large-scale genomic datasets or have limited computational resources, RFMix-reader offers an efficient and memory-conscious solution for reading and processing RFMix output files. Its lazy loading approach ensures optimal resource utilization, making it a valuable tool for researchers and bioinformaticians working with admixed population data.

Simulation Data

Simulation data is available for testing two and three population admixture on Synapse: syn61691659.

Usage

This works similarly to pandas-plink:

Two Population Admixture Example

This is a two-part process.

Generate Binary Files

To reduce computational time and memory, we leverage binary files. While RFMix does not generate these directly, we provide a function for their creation: create_binaries. This function can also be invoked via the command line: create-binaries [-h] [--version] [--binary_dir BINARY_DIR] file_path.

bash create-binaries two_pops/out/ This will generate the binary files in a location './binaryfiles" as `--binarydir` is an optional parameter.

```python from rfmixreader import createbinaries

Generate binary files

filepath = "twopops/out/" binarydir = "./binaryfiles" createbinaries(filepath, binarydir=binarydir) ```

You can also do this on the fly.

```python from rfmixreader import readrfmix

filepath = "twopops/out/" binarydir = "./binaryfiles" loci, rfq, admix = readrfmix(filepath, binarydir=binarydir, generatebinary=True) ```

We do not have this turned on by default, as it is the rate limiting step. It can take upwards of 20 to 25 minutes to run depending on *fb.tsv file size.

Main Function

Once binary files are generated, you can the main function to process the RFMix results. With GPU this takes less than 5 minutes.

```python from rfmixreader import readrfmix

filepath = "twopops/out/" loci, rfq, admix = readrfmix(filepath) `` **Note:**./binaryfilesis the default forbinary_dir`, so this is an optional parameter.

Three Population Admixture Example

RFMix-reader is adaptable for as many population admixtures as needed.

```python from rfmixreader import readrfmix

filepath = "examples/threepopuations/out/" binarydir = "./binaryfiles" loci, rfq, admix = readrfmix(filepath, binarydir=binarydir, generatebinary=True) ```

Loci Imputation

Imputing local ancestry loci information to genotype variant locations improves integration of the local ancestry information with genotype data. As such, we provide the interpolate_array function to efficiently interpolate missing values when local ancestry loci information is converted to more variable genotype variant locations. It leverages the power of Zarr arrays, making it suitable for handling substantial datasets while managing memory usage effectively.

Features

• CUDA Acceleration: Uses CUDA for performance enhancement when available; otherwise, it defaults to NumPy.
• Chunk Processing: Processes data in manageable chunks to optimize memory usage, making it ideal for large datasets.
• Progress Monitoring: Displays progress through a tqdm progress bar, providing real-time feedback during execution.
• Column-wise Interpolation: Employs the _interpolate_col function to perform interpolation along each column of the dataset.

Example Usage

```python import pandas as pd import dask.array as da

Outer merged dataframe of loci and variant locations

"i" is from the loci information; "chrom" and "pos" from both dataframes

variantlocidf = pd.DataFrame({'chrom': ['1', '1', '1', '1'], 'pos': [100, 200, 300, 400], 'i': [1, NA, NA, 2]})

Dask array of admixture data, which will have few rows than variantlocidf

admix = da.random.random((2, 3)) # Random data here

This expands the Dask array (admix) and interpolates missing data

Default chunksize = 50,000 assuming variantloci_df 6-9M rows.

Default batch_size = 10,000 assuming admix loci from 2-4M rows.

Adjust this based on variantlocidf size.

z = interpolatearray(variantlocidf, admix, '/path/to/output', chunksize=100, batch_size=100)

Check the shape of the resulting Zarr array, which should have the same

row numbers as variantlocidf

print(z.shape) # Output: (4, 3) ```

Example Preprocessing Functions

The helper functions _load_genotypes and _load_admix are designed to facilitate the loading of loci and genotype data for constructing the variant_loci_df DataFrame.

1. _load_genotypes(plink_prefix_path): This function uses the tensorqtl library to read genotype data from PLINK files (PGEN). It returns both the loaded genotype data and a DataFrame containing variant information, which includes chromosome and position details. The chromosome identifiers are formatted to include the "chr" prefix for consistency.
2. _load_admix(prefix_path, binary_dir): This function employs the rfmix_reader library to load local ancestry data from specified paths. It reads the ancestry information into a suitable format for further processing, enabling integration with genotype data.

These functions ensure accurate loading and formatting of variant and local ancestry data, streamlining subsequent analyses.

```python def loadgenotypes(plinkprefixpath): from tensorqtl import pgen pgr = pgen.PgenReader(plinkprefixpath) variantdf = pgr.variantdf variantdf.loc[:, "chrom"] = "chr" + variantdf.chrom return pgr.loadgenotypes(), variantdf

def loadadmix(prefixpath, binarydir): from rfmixreader import readrfmix return readrfmix(prefixpath, binarydir=binarydir)

def testing(): basename = "/projects/b1213/largeprojects/braincolocapp/input" # Local ancestry prefixpath = f"{basename}/localancestryrfmix/m/" binarydir = f"{basename}/localancestryrfmix/m/binaryfiles/" loci, , admix = _loadadmix(prefixpath, binarydir) loci.rename(columns={"chromosome": "chrom", "physicalposition": "pos"}, inplace=True) # Variant data plinkprefix = f"{basename}/genotypes/TOPMedLIBD" _, variantdf = loadgenotypes(plinkprefix) variantdf = variantdf.dropduplicates(subset=["chrom", "pos"], keep='first') # Keep all locations for more accurate imputation variantlocidf = variantdf.merge(loci.topandas(), on=["chrom", "pos"], how="outer", indicator=True)\ .loc[:, ["chrom", "pos", "i", "merge"]] datapath = f"{basename}/localancestryrfmix/m" z = interpolatearray(variantlocidf, admix, datapath) # Match variant data genomic positions arrgeno = arrmod.array(variantlocidf[~(variantlocidf["merge"] == "rightonly")].index) newadmix = z[arr_geno.get(), :] ```

Note: Following imputation, variant_df will include genomic positions for both local ancestry and genotype data.

Author(s)

• Kynon JM Benjamin

Citation

If you use this software in your work, please cite it.

Benjamin, K. J. M. (2024). RFMix-reader (Version v0.1.15) [Computer software]. https://github.com/heart-gen/rfmix_reader

Kynon JM Benjamin. "RFMix-reader: Accelerated reading and processing for local ancestry studies." bioRxiv. 2024. DOI: 10.1101/2024.07.13.603370.

Funding

This work was supported by grants from the National Institutes of Health, National Institute on Minority Health and Health Disparities (NIMHD) K99MD016964 / R00MD016964.