Whole Genome Sequencing (WGS 30x) has revolutionized personalized medicine and scientific research by allowing 100% of your DNA to be analyzed. However, behind every health or wellness report, there is a massive amount of complex bioinformatics data. If you have decided to download your raw genomic data, it is very likely that you have come across different file extensions, with the CRAM file being one of the most important and efficient.
What is a CRAM file and what is its role in WGS?
The CRAM file is a highly compressed format used to store genomic sequencing data previously aligned against a reference genome.
To understand its place within the bioinformatics workflow, it is helpful to differentiate it from other formats:
- Compared to the FASTQ file: While the FASTQ file contains the raw data generated directly by the sequencing machine without processing, the CRAM file represents a much later stage.
- Aligned reads: In the CRAM, the DNA reads have already been processed, which means that each fragment has information about its exact position within the reference genome, along with the associated quality scores.
This format is widely used by bioinformaticians, geneticists, and researchers looking to perform advanced analyses, such as identifying genetic variants, reviewing specific regions of the genome, or validating findings, as well as by advanced users who wish to keep an optimized and compact version of their WGS data.
Key features of the CRAM file
The CRAM format stands out in the clinical and research genomics environment thanks to several fundamental technical advantages:
- High compression: Thanks to its advanced compression system, it takes up remarkably less storage space than other traditional aligned formats (such as BAM).
- Aligned reads: It stores the position of each read against the reference genome in a structured manner.
- Quality information: It preserves the technical metadata and quality scores essential for auditing the reliability of the sequencing.
- Storage efficiency: It is the ideal format for managing the massive volumes of data generated by Whole Genome Sequencing (WGS).
Limitations to keep in mind
Due to its technical nature and focus on computational processing, the CRAM file has certain particularities:
- Reference genome dependency: To correctly read and interpret a CRAM file, it is essential to have the exact same reference genome that was used during the initial alignment. At tellmeGen, we use "GRCh37.primary_assembly.genome.fa.gz" as our reference genome.
- Not human-readable: It cannot be opened directly as a text document to check genetic traits or predispositions. It requires specialized software for visualization.
- Requires technical knowledge: It is specifically designed for advanced profiles, bioinformaticians, or professionals familiar with genomic data manipulation.
Available formats and downloading at tellmeGen
At tellmeGen we believe in transparency and the ownership of your genetic data. For this reason, in addition to the CRAM file, we offer our users the ability to download other complementary technical formats such as FASTQ and VCF directly from the user area of your account.
Technical requirements for working with CRAM files
If you are a user or researcher and plan to work with your WGS CRAM files, we recommend taking the following hardware and software requirements into account:
- Operating system: Using Linux or macOS is recommended, although it is also possible to use them on Windows through compatible tools or environments like WSL (Windows Subsystem for Linux).
- Specific software: It is necessary to have specialized bioinformatics tools such as samtools, IGV (Integrative Genomics Viewer), or bcftools.
- RAM: Having a minimum of 32 GB of RAM is advised to smoothly manage the data volumes of a WGS.
- Storage: Although the CRAM file stands out for its high compression, handling whole genomes requires disks with ample available capacity.
The CRAM file is the ultimate tool for those advanced users looking to maximize the performance of their DNA test, allowing for an efficient, detailed, and optimized technical analysis of their entire DNA.
