Compact Genome Format
The scientific community is reaching an era of inexpensive whole genome sequencing, often with analysis focusing on annotated genome variants. We anticipate researchers and physicians will want to efficiently query, visualize, and analyze 100’s - 100,000’s of genomes at a time. Thus, we present a new format, Compressed Genome Format (CGF), designed for losslessly storing phased or unphased genetic variation data that can be queried and analyzed without decompression. Our preliminary implementation of CGF represents chromosomes 13 and 17 of 174 whole genome sequences, from 41.2-52.1 MB to 7.0-7.4 MB. Loading these 174 people to a format conducive to machine learning uses 1.805 GB and takes on average 33.37s. Projection onto the first principal component separated the population according to ancestral geographical location, as documented by the 1000 Genomes Project Consortium to occur for human SNP data. CGF also supports a GA4GH Beacon, is compatible with other GA4GH API, adapts easily to changes in the reference genome, can be losslessly visualized, and can be easily annotated.
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Compact Genome Format
- 1. An Open-Source Format for Personal Genome Representation Enabling Fast Queries and Analyses of Human Genomes Compact Genome Format Sally Guthrie, Research Scientist, Curoverse (sguthrie@curoverse.com)
- 2. ACKNOWLEDGEMENTS Alexander Wait Zaranek, Chief Scientist, Curoverse Abram Connelly, Research Scientist, Curoverse
- 3. CURRENT USES OF GENOMIC DATA Patient Care • Analyze one genome for rare and pathogenic variants Population Analysis • Examine a population for rare variants • Separate a population into subgroups • Case/Control Studies and GWA Studies • Can require merging multiple data sets • Can require using supervised and unsupervised machine learning
- 4. VARIANT CALL FORMAT (VCF) SNAPSHOT Advantages • Very flexible • Easily annotated with canonical or in-house annotation pipelines • Can be small (with compression) Disadvantages • Difficult to merge VCFs between studies • Can be slow to query and run machine learning algorithms on (requires pre-processing)
- 5. WHAT IS COMPACT GENOME FORMAT (CGF)? Compact Genome Format is a compressed genomic sequence Allows analysis to be run on the compressed data Represents a sequence using a series of vectors • Each position in the vector is termed a “tile” • The value of the vector points to a sequence in a “Tile Library,” a pan-genome
- 6. GENERATING THE REFERENCE TILE LIBRARY Human Reference Genome (with tag sets highlighted) Tag Set: … 1. Choose a tag set of unique 24-base long sequences 2. Map tag set to a reference genome
- 7. GENERATING THE REFERENCE TILE LIBRARY 1. Save sequence between each tag pair to the tile library 2. Give these sequences a value (0) Tile Position Id 00.0000 00.0001 00.0002 … …
- 8. EXTENDING THE TILE LIBRARY …010020… …011031… Tile Library Tile Position Id 00.002b 00.002c 00.002d 00.002e 00.002f 00.0030 ……
- 9. EXTENDING THE TILE LIBRARY …00201*… …1*11**… Tile Library Tile Position Id 00.002b 00.002c 00.002d 00.002e 00.002f 00.0030 ……
- 10. RATE OF GROWTH OF THE TILE LIBRARY
- 11. CGF AND TILE LIBRARY FACILITATE Requires: beginning locus and end locus Returns: the sequences between the two loci for all people in the population Queries on Sequences
- 12. TIME USED FOR QUERIES ON SEQUENCES
- 13. TIME PER BASE FOR QUERIES ON SEQUENCES
- 14. CGF FACILITATES SEVERAL IMPORTANT ANALYSIS TYPES Unsupervised Machine Learning Supervised Machine Learning (Case/Control) GWAS Encompass all variation, not just SNP variation
- 15. COMPACT GENOME FORMAT FINAL THOUGHTS • Allows annotations Tile Library can be annotated by canonical and in- house annotation pipelines, thus automatically applying annotations to all CGF files • Small • Standardized • Fast to query • Designed for machine learning
- 16. Thank you! Any Questions? Preliminary implementation: lightning-dev3.curoverse.com/brca Source code: https://github.com/curoverse/lightning Software license: GNU AGPLv3
- 17. GENERATING THE REFERENCE TILE LIBRARY WITH MULTIPLE TAG SETS Tag Set ……Tag Set
- 18. RATE OF GROWTH OF THE TILE LIBRARY (NO CALLS CREATE VARIANTS)