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+# Working with Reference Genome
+
+This guide explains how to import, manage, and extract VCF files using ODM APIs, with a focus on working with different
+reference genomes. ODM is a flexible platform that allows users to work with various species by importing custom
+reference genomes.
+
+## **Variant files and Reference Genomes**
+
+### **Description of VCF files**
+
+VCF (Variant Call Format) is a standardized file format for storing DNA sequence variations detected in genomic sequencing data. It is both human-readable and machine-parsable, making it widely adopted in genomics.
+
+A VCF file includes:
+
+* **Header**: Contains metadata, including the reference genome, version, and description of each column.
+* **Body**: Contains the actual variant data. Each row represents a variant.
+
+#### **Important Columns in the VCF Body:**
+
+* **CHROM**: Chromosome of the variant
+* **POS**: Genomic coordinate
+* **ID**: Variant identifier (e.g., dbSNP ID)
+* **REF**: Reference base(s)
+* **ALT**: Alternative base(s)
+* **QUAL**: Confidence score of the variant
+* **FILTER**: Filter status
+* **INFO**: Additional annotations (e.g., allele frequency)
+* **FORMAT & Sample Data**: Genotype details for each sample
+
+
+The VCF format contains detailed information about the variants, positions, and genotypes
+
+For more details and examples of VCF files, refer to the section [Supported File Formats](../doc-odm-user-guide/supported-formats.md)
+
+### **Reference Genomes**
+
+A reference genome is a representative example of a species’ DNA sequence that serves as a baseline for comparing and interpreting sequencing data. In variant analysis, sequencing reads are aligned to the reference genome to identify differences such as single-nucleotide polymorphisms (SNPs), insertions, deletions, and structural variations.
+
+In ODM, the reference genome plays a crucial role during the import of variant files (e.g., VCF). It is used to **index variants**, map their positions to specific genomic regions, and annotate them with gene information when available. This indexing enables advanced features such as:
+
+* **Gene-based variant search**: Users can search for variants by specifying gene names, even if the original VCF file does not include gene annotations.
+* **Accurate interpretation of genomic intervals**: Variants can be analyzed in the context of known gene structures (exons, introns, UTRs, etc.).
+
+By default, ODM uses the **GRCh38** human reference genome. However, users can:
+
+* **Import other versions of human reference genomes** (e.g., GRCh37) if needed for compatibility with legacy datasets.
+* **Add custom reference genomes** in **GTF (Gene Transfer Format)** for non-human organisms, enabling similar search and annotation functionality.
+
+## **Importing Custom Reference Genomes**
+
+Users can import their reference genomes into ODM using the API to work with species-specific or non-standard genomic data. This is particularly useful for non-human studies or for datasets aligned to alternative versions of a genome.
+
+Before importing a new reference genome, users are encouraged to **check which reference genomes are already available** in the system. This helps avoid duplication and ensures consistency across datasets. Users can:
+
+* Browse existing reference genomes in the **File Browser** (under the Reference Genomes category), or
+* Use the API endpoint: `GET /api/v1/reference-genomes.` This returns a list of reference genomes currently registered in the system.
+
+{width=70%}
+Users can explore the existing Reference genomes by opening the File Manager in the GUI or via the endpoint GET /api/v1/reference-genomes
+
+### **Required File Format**
+
+If the reference genome needed is not listed in the **File Browser** or returned by the `GET /api/v1/reference-genomes` endpoint, users can import a custom reference genome into ODM to support their dataset.
+
+Custom reference genomes must be provided in **Gene Transfer Format (GTF)** and compressed as **.gtf.gz**. This format includes essential gene structure information such as:
+
+* Exons
+* Introns
+* Coding regions
+* Transcription start and end sites
+
+### **Source for Reference Genomes**
+
+Custom genomes can be obtained from:
+
+* **Ensembl**
+* **NCBI**
+* **Custom in-house assemblies**
+
+### **Import Steps**
+
+1. Use the endpoint: `POST /api/v1/reference-genomes`
+
+2. Provide the required details, including:
+ * **annotationUrl**: URL to the GFT file of the genome annotation file (compressed in .gtf.gz format).
+ * **organism**: Scientific name of the species (e.g., *Mus musculus*).
+ * **assembly**: Genome assembly version (e.g., Zm-B73-REFERENCE-NAM-5.0).
+ * **release**: Minor version of the reference genome.
+ * **name**: A custom title for the reference genome, typically derived from species, assembly, and release details
+
+
+The POST /api/v1/reference-genomes
endpoint allows users to upload custom reference genomes into ODM
+
+**Request Example**:
+
+``` json
+{
+ "annotationUrl": "https://ftp.ensembl.org/pub/release-114/gtf/mus_musculus/Mus_musculus.GRCm39.114.gtf.gz",
+ "organism": "Mus musculus",
+ "assembly": "GRCm39",
+ "release": "114",
+ "name": "Mouse GRCm39 Ensembl 114"
+}
+```
+
+**Response Example**:
+
+``` json
+{
+ "genestack:accession": "GSF1284255"
+}
+```
+
+This response confirms successful import and provides a unique **accession ID**.
+
+The newly imported reference genome is now available in ODM and visible in the File Manager.
+
+{Width=90%}
+The File Manager displays imported reference genomes along with other files in the ODM instance
+
+## **Importing VCF Files with custom Reference Genomes into ODM**
+
+Once the reference genome is imported, users can upload VCF files and link them to the appropriate genome.
+
+### **Preparing Metadata**
+
+To upload VCF files, you must also provide a metadata file in TSV (tab-separated values) format. This file should include at least the following fields:
+
+* **Genome Version**: The exact name of the reference genome as it appears in ODM
+* **Organism**: The species associated with the genome
+
+| Genome Version | Organism |
+|------------------------------|---------------|
+| Mouse GRCm39 Ensembl 114 | Mus musculus |
+
+Additional optional fields, such as **Version**, **Accession**, or **User**, may also be included and will not interfere with the upload. The system is flexible and accepts metadata files with varying numbers of columns.
+
+??? note "Note"
+
+ Here are examples of metadata files with different numbers of features (columns).
+
+ - **3 columns**: [Metadata_Mm_3columns.tsv (S3 link)](s3://bio-test-data/Metadata_Mm_3columns.tsv), [Download via HTTPS](https://bio-test-data.s3.us-east-1.amazonaws.com/Metadata_Mm_3columns.tsv)
+ - **5 columns**: [Metadata_Mm_5columns.tsv (S3 link)](s3://bio-test-data/Metadata_Mm_5columns.tsv), [Download via HTTPS](https://bio-test-data.s3.us-east-1.amazonaws.com/Metadata_Mm_5columns.tsv)
+ - **11 columns**: [Metadata_Mm_11columns.tsv (S3 link)](s3://bio-test-data/Metadata_Mm_11columns.tsv), [Download via HTTPS](https://bio-test-data.s3.us-east-1.amazonaws.com/Metadata_Mm_11columns.tsv)
+
+
+A metadata file in tabular format ensures the VCF file is linked to the correct reference genome
+
+### **API Upload Procedure**
+
+To upload VCF files into ODM, use the same **standard import endpoint** employed for other bulk data types such as transcriptomics, libraries, samples, and flow cytometry.
+
+Use the endpoint: `POST /api/v1/jobs/import/variant`
+
+{width=80%}
+The POST /api/v1/jobs/import/variant
endpoint is used to import gene variant files
+
+**Request Example**:
+
+``` json
+{
+ "metadataLink": "s3://MyBucket/SRL_ReferenceGenomes/Metadata_Mm_5columns.tsv",
+ "dataLink": "s3://MyBucket/SRL_ReferenceGenomes/Test_gVCF_Mm.vcf",
+ "templateId": "GSF1574668"
+}
+```
+
+As with other data types, the request should include:
+
+* A **metadata file** with information about the reference genome and organism
+* A **VCF file** compressed **.vcf.gz** or plain **.vcf** (See example of a [VCF file](https://bio-test-data.s3.us-east-1.amazonaws.com/gVCF_Mm_Demo.vcf))
+* A **link structure** connecting the data to samples, libraries, or preparations
+
+!!! note "Important"
+ Unlike transcriptomics or flow cytometry data, **a reference genome must be specified** when importing VCF files. If no metadata is provided, the system defaults to using the **human reference genome (GRCh38)**. To use a different genome, you must include a metadata file where the **Genome Version** matches the name of a **previously imported custom reference genome** in your ODM instance.
+
+### **Tracking Job Status**
+
+Once submitted, you can track the import job status via:
+
+Endpoint: `GET /api/v1/jobs/{jobExecId}/output`
+
+{Width=80%}
+The endpoint GET /api/v1/jobs/{jobExecId}/output
retrieves job execution details
+
+### **Completion and Accession ID**
+
+Once completed, the system assigns an accession number to the imported file.
+
+**Response Example**:
+
+``` json
+{
+ "status": "COMPLETED",
+ "result": {
+ "groupAccession": "GSF1574797"
+ }
+}
+
+```
+
+## **Verifying the Reference Genome Used for Variant Indexing**
+
+After uploading a VCF file, users may want to confirm which reference genome was used during indexing, especially important when working with **custom reference genomes**.
+
+**How to Check the Reference Genome**
+
+Use the following API endpoint to retrieve details about the indexed variant group:
+
+Endpoint: `GET /api/v1/as-user/variants/group/{id}`
+
+
+Use the endpoint GET /api/v1/as-user/variants/group/{id}
to retrieve information about variant groups
+
+Replace **{id}** with the **group accession** of your imported VCF file (e.g., GSF1278671).
+
+The response includes metadata about the variant group. Scroll to the bottom of the response to find the referenceGenome section, which provides full details:
+
+{Width=80%}
+The endpoint displays details of the variant files, including the reference genome
+
+#### **Key Fields to Review**
+
+* **name**: Name of the reference genome used
+* **organism**, **assembly**, **release**: Core genome attributes
+* **annotationUrl**: Link to the annotation file used (e.g., GTF from Ensembl)
+* **genestack:accession**: ODM accession for the reference genome
+* **initializationStatus**: Should be COMPLETE if the genome is ready for use
+
+This information helps ensure that the variant data was indexed against the correct reference genome, particularly when working across multiple organisms or custom genome builds.
+
+## **Linking VCF Files to Sample Metadata**
+
+Once the VCF file is imported, it needs to be linked to the corresponding sample metadata records to make the variant data accessible and meaningful in the ODM interface.
+
+The linking process is **identical** regardless of whether the file uses a **custom** or **default** reference genome.
+
+To link the variant file to samples, follow the **standard linkage procedure** used for other data types. For detailed steps, see [*Linking Data to Samples*](user-guide/quick-start/contributor-api.md#linking-your-entities).
+
+**API Endpoint:**
+
+`POST /api/v1/as-curator/integration/link/variant/group/{sourceId}/to/sample/group/{targetId}`
+
+You will need to provide:
+
+* **Source ID**: the accession of the VCF file group (e.g., GSF1278671)
+* **Target ID**: the accession of the sample metadata group (e.g., GSF1278546)
+
+### **Confirming a Successful Link**
+
+Once the VCF file is linked to the sample metadata, the variant data becomes accessible both in the **ODM interface** and via the **API**.
+
+#### **In the ODM Interface**
+
+You can explore the data in the **Gene Variant Data** section of ODM. If the file is successfully linked, you’ll see the variants associated with your samples, organized by gene or genomic feature.
+
+{Width=80%}
+Successfully imported and linked VCF files can be explored in ODM’s Gene Variant Data section
+
+#### **Using the API**
+
+To confirm that your variant data is correctly indexed and linked to a gene from your **custom reference genome**, you can query the API directly.
+
+**Endpoint:**
+
+`GET /api/v1/as-user/variants`
+
+Use the variantInfo parameter to filter results by gene or feature. For example:
+
+```
+variantInfo
+info.GENE=Il2ra
+```
+
+This query retrieves all variant records associated with the gene **Il2ra** (interleukin 2 receptor, alpha chain), based on the annotation from your custom reference genome.
+
+The response will include:
+
+* Variant positions
+* Genotypes
+* Associated sample IDs
+* Additional metadata from the VCF file
+
+
+Example query using variantInfo, info.GENE=Il2ra showing the resulting variant data
+
+ODM streamlines the management of genetic variant data by supporting custom reference genomes, VCF file import, and metadata linkage. Whether you’re working with human or non-human species, ODM ensures that variant data is well-organized and ready for analysis.
diff --git a/mkdocs.yml b/mkdocs.yml
index 221a331..8a124c9 100644
--- a/mkdocs.yml
+++ b/mkdocs.yml
@@ -38,6 +38,7 @@ nav:
- Sharing Studies: user-guide/doc-odm-user-guide/sharing.md
- Getting a Genestack API token: user-guide/doc-odm-user-guide/getting-a-genestack-api-token.md
- Supported File Formats: user-guide/doc-odm-user-guide/supported-formats.md
+ - Working with Reference Genome: user-guide/doc-odm-user-guide/variants.md
- Tools:
- odm-sdk: