Add new case page > Family tree screen > Add patient information panel > Add sample section

You can choose one of the following options:

1. Existing sample - pick one of the samples already loaded on the platform

2. Upload New Sample - upload files from your PC and enter sample name

3. Choose from storage - choose files from your cloud storage and enter sample name

4. No sample - postpone uploading files but proceed with case creation or skip uploading files for family members other than Proband

Add new case page > Select sample type screen.

You can select the sample's file type from the given options:

1. FASTQ: .fastq.gz, .fq.gz, .bam, .cram.

2. Project VCF: .pvcf, .vcf, .vcf.gz, .pvcf.gz

3. VCF: .vcf, .vcf.gz.

Add new case page > Family tree screen > Add patient information panel > Patient info section

1. Fill in the boxes:

1. Sex (33.0+) / Gender (≤32.0) (*)

Options: Male, Female, Unknown.

2. Relationship

The default fixed value for Proband is Test Subject.

3. Date of Birth

Expected format: mm/dd/yyyy.

4. Medical Condition (*)

Options: Affected, Healthy.

The default value for Proband is Affected, but you may change it to Healthy.

5. Proband Phenotypes (*)

To add all relevant phenotypes for the Proband, use one of the following methods:

1. One by one (Selection mode),

2. In a batch (Batch mode),

3. Extract HPO terms from the file uploaded in the Clinical Notes section, or

4. Automatically infer disease-associated phenotypes (see Proband Suspected Disease Condition below).

Selection mode

Please follow the steps described below for each phenotype:

1. Enter an HPO term (e.g., Hypoplasia of the ulna), an HPO ID (e.g., HP:0003022), or a descriptive phenotype name (e.g., Underdeveloped ulna) in the search box.

2. Select a matching term from a dropdown menu and press Complete after you've added all the terms and additional patient information below.

Batch mode

Paste a list of comma-separated HPO terms or HPO IDs (🆕32.0+) in the search box and press Complete.

Extract HPO terms from the file uploaded in the Clinical Notes section

In the Clinical Notes section upload a description of the clinical presentation in .pdf, .xls, .txt, .doc, .jpeg, or .jpg format. Among the extracted HPO terms for Phenotypes and Diseases select the ones you want to add to Proband's Phenotypes.

6. Proband Suspected Disease Condition.

Enter the disease name in the search box, select a matching term from a dropdown menu and press Complete. All the associated phenotypes will be automatically added to the Proband Phenotypes. To remove any phenotype described for the disease but not observed in your patient, click the ☒ button next to the HPO term in the Proband Phenotypes list.

7. Suspected Disease Penetrance

Enter the suspected disease penetrance as a percentage.

8. Suspected Disease Severity

Select the appropriate category to indicate the severity of the disease symptoms observed in the patient: Mild, Moderate, Severe, Profound.

9. Consanguinity

Mark the checkbox if applicable.

10. Patient Ethnicities

Paternal and Maternal. Enter the ethnicity name in the search box and select a matching term from a dropdown menu.

2. ​Click on Complete once all the information is added.

This section will guide you through adding new cases to the Emedgene platform.

Please follow the steps as described below:

1. Click on the Add new case button on the Top navigation panel.

2. At the Select sample type page, select the file type for your case analysis. Click Next to proceed to the Family tree panel.

3. The page is divided into two panels: Create family tree (left) and Add patient information (right).

1. In the Create family tree panel (left):

   • Build a pedigree using the visual tool;

   • Add Clinical Notes (optional) in a free text panel. In this section, you can record additional clinical information that does not fall under the other categories or provide further details that can give context and help solve the case.

   • You have an option to upload a file that includes description of the clinical presentation (.pdf, .xls, .txt, .doc, .jpeg, .jpg formats are supported). HPO terms for Phenotypes and Diseases are extracted from the files and can be added to Proband's Phenotypes in Patient info section.

   • You may select suspected Inheritance mode(s). This is for the case record and won't be used during analysis.

   • Select whether you want Secondary findings in Proband to appear in the AI Shortlist analysis results (checkbox).

1. In the Add patient information panel (right) for each of the family members:

   • Add a sample;

   • Fill in a sample name (for cases starting from VCF, this must correspond to the corresponding proband or family member header within the file);

   • Fill in the required patient details;

   • Click Next to proceed to the Case info screen.

1. In the Case info screen:

   • Select case type (Custom Panel, Exome, Whole Genome, or other). When running cases as Exome, variants outside exons ±50 bp are filtered out and won't appear in the results.

   • Pick whether you want Carrier Analysis to be carried out (checkbox). Carrier analysis requires you to provide us with a targeted genes list.

   • Sequencing Information (Choose from existing kit, No kit). You can indicate if there was an Enrichment Kit used if you wish to compare the breadth and depth of coverage to that expected for the kit used. RefSeq coding regions will be used as a reference if no kit is provided. This option is relevant for Custom Panel and Exome case types. In the Kit info section, fill in the Enrichment Kit and optionally Lab, Machine, Sequencing reagents, and Expected coverage.

   • Select genes list (All genes, Phenotype based genes, Existing gene list, Create a new gene list) - indicate if you want the analysis to be limited to a specified list of genes.

   • Select preset group: We can implement different combinations of Presets to be used for different case types (i.e. Presets for exome may be different from Presets for genome) as defined by your SOPs to further streamline case review.

     🆕 34.0+: If the user does not select a Preset group, the system automatically assigns the default Preset group to the case. The default Preset group is indicated by the word "default" in parentheses after its name.

   • Confirm subject consent for extended sharing (32.0+).

   • Optional: Additional case info:

     • Indication for testing. Add free-text notes.

     • Label. Add labels to your case. You can choose among the labels created beforehand by your organization's manager. Labels cannot be added after case creation.

   • Summary: confirm the selected case type and genes list before completing case creation.

   • Click Next to complete case creation.

1. In the Done screen:

   • The Case ID is displayed;

   • Add participants to your case - subscribe your colleagues to notifications on Case status change.

Emedgene provides the tightest integration with DRAGEN for germline variation analysis, providing accuracy, comprehensiveness, and efficiency, spanning variant calling through interpretation and report generation.

Compatibility with DRAGEN Variant Callers

Extensive Compatibility with Additional Variant Callers

The Emedgene platform supports a variety of variant callers and applies specific quality parameters for each. The quality assessment is an essential step in the Emedgene pipeline because variants with low quality will not be considered by the AI components.

If the variant caller is not supported or not recognized, a default quality function will be applied. The default parameters are built on GT (genotype), depth (DP) and allele bias (AB). These fields are mandatory, and their absence will induce “Low quality” for all variants.

The following variant callers are currently supported on the Emedgene pipeline, providing a header with the variant caller command line should be present within the VCF headers.

Additional callers can be supported on demand.

> Case info screen > Select genes list

Select gene list

You can limit analysis to a gene list in the platform while creating a case. Choose between:

1. All genes

No limitation of the analysis.

2. Phenotype based genes

The list is automatically built from genes related to the HPO terms you entered for the case (per Emedgene knowledge base).

3. Existing gene list

Select one of the previously added gene lists from a dropdown list.

4. Create a new gene list

Generate a new virtual panel: add a List title and then add all the gene symbols one by one () or in a batch ().

Selection mode

For each gene please follow the steps described below: Enter a gene symbol in the search box in the right panel (Candidate Genes) and select a matching symbol from a dropdown menu.

Batch mode

After selecting batch mode, paste a list of comma-separated gene symbols in the search box in the right panel (Candidate Genes).

Gene list modes

You can choose between two different modes of a gene list feature:

1. Gene panel mode

The default option.

Analysis is limited to the selected gene panel, no variants in other genes are considered in the results. If this in silico panel is used for analysis of exome or genome data, the gene restriction may be lifted during manual analysis to "open-up" the entire exome or genome for analysis.

2. Boost genes mode

Enabled through checkbox.

Analysis is performed for variants in all the genes. Variants in the targeted genes get upgraded scores during prioritization by the AI Shortlist algorithm.

How to filter variants by a gene list

1. Candidate Genes filter

2. Gene Lists filter created in a case

3. Gene Lists filter created in Settings

First, fill in the List title and click Add button. Then add the gene symbols one by one (Selection mode) or in a batch (Batch mode).

• Selection mode - for each gene please follow the steps described below: Enter a gene symbol in the search box (Candidate Genes) and select a matching symbol from a dropdown menu.

• Batch mode: Paste a list of comma-separated gene symbols in the search box (Candidate Genes).

When you finished, press Save.

To view the Gene list in read-only mode, click on its name. By pressing the corresponding icons next to the Gene list's name, you can duplicate, edit or delete it. If a gene list has already been used by a case in the platform, you will only have the possibility to duplicate it.

> Family tree screen > Create family tree panel

Build a pedigree via the visual tool.

It is ideal that a proband selected for case analysis is affected and has disease phenotype(s).

You can add a Father, a Mother, a Sibling, or a Child to any family member, starting with the Proband. To do this, choose their icon, then click on the Add family member button in the bottom right corner of the pedigree builder to select a family member.

To delete a family member, choose their icon, then click on the Delete Subject button in the top right corner of the Add patient information panel.

> Family tree screen > Create family tree panel > Show Secondary Findings

While creating a case, you can choose if you want Secondary (Incidental) findings in the Proband to appear in the results.

These are known or expected pathogenic variants in the genes that are unrelated to the primary purpose of the testing. The secondary finding genes list includes:

> Family tree screen > Add patient information panel > Patient info section

1. Fill in the boxes:

1. Sex (33.0+) / Gender (≤32.0) (*)

Options: Male, Female, Unknown.

2. Relationship

Indicates the family relationship of a subject to the Proband automatically inferred from the pedigree. Options: Father, Mother, Sibling, Child, Other.

3. Date of Birth

Expected format: mm/dd/yyyy.

4. Ignore Sample

Mark the checkbox if you want to exclude the sample from the AI Shortlist analysis and Inheritance filters while preserving genotype data.

5. Add Proband's phenotypes

If a sample shares some phenotypes with the Proband, you can copy them by checking this box. Proband's phenotypes will appear in a newly created Related Phenotypes section. To remove any of the proband's phenotypes not observed in a current individual, click the ☒ button next to the HPO term in the Related Phenotypes section.

6. Unrelated Phenotypes

Selection mode

Please follow the steps described below for each phenotype:

• Enter an HPO term (e.g., Hypoplasia of the ulna), an HPO ID (e.g., HP:0003022), or a descriptive phenotype name (e.g., Underdeveloped ulna) in the search box;

• Select a matching term from a dropdown menu and press Complete after you've added all the terms.

Batch mode

Paste a list of comma-separated HPO terms or HPO IDs (🆕 32.0+) in the search box and press Complete.

2. Click on Complete once all the information is added.

While adding a new case, you will build a pedigree and annotate each of the samples with data required for analysis ( > Family tree screen).

After the case has been created, the family tree is available in the panel (righthand panel of the Cases page).

Family tree legend:

1. Icon fill color in other pedigree members indicates the presence or absence of the proband's phenotypes in a present sample (regardless of the potential presence of additional unrelated phenotypes):

   • Filled - the individual is affected by all of the proband's phenotypes;

   • Half-filled - the individual is affected by some of the proband's phenotypes;

   • Empty - the individual is not affected by any of the proband's phenotypes.

2. Icon color intensity denotes whether sample files have been uploaded for the particular individual:

   • Full color - the sample has files loaded in the case;

   • Faded color - no sample files are available.

3. Icon line type indicates whether the sample is considered or excluded during analysis (relevant to samples with uploaded files only):

   • Solid - the sample is included in the analysis;

   • Dashed - the sample is ignored by Inheritance filters and the AI Shortlist algorithm, but you still can explore its genotypes. ​

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Ethnicities of the proband's mother and father can be specified during the UI case creation. Starting from version 32.0.0, this can also be accomplished via API case creation. Please refer to the following list of supported ethnicities.

Version 33.0+:

With version 33.0 and later, you have the flexibility to manage Case labels at any time: create, add, or remove them directly in the Cases table.

Versions older than 33.0:

The organization's custom Case labels must be assigned while creating a case, in the Case info screen of the Add new case flow.

The desired Case labels should be created prior to case creation by the organization's manager in the Organization settings.

Once a case is created, Case labels cannot be removed or added.