Creating a case

Creating new cases is simple. Just go to the All cases section and select Create a new case.

Create a new case form has now opened, allowing you to enter all needed information for the analysis.

Create a new case form

When entering the Create a new case form, you will be asked to fill in information about the patient and analysis as well as uploading the VCF files for the case. You will be able to upload VCF files containing small variants (SNVs) and copy-number-variants (CNVs) for the patient. You will also have the opportunity to upload additional VCFs containing SNVs for the parents in case of a trio. General info allows you to input in sex, Date of Birth (DOB), symptoms in the Human Phenotype Ontology (HPO) and if needed, in silico panels to restrict the analysis to certain genes only.

See below for in-depth explanations of each section.

Case ID

The case ID will serve as a reference to identify the case in the Results section. All formats are accepted but we recommend to use pseudonymized information in a standard format such as “NOS-200801-01” or “P20-1000A”, as this allows you to filter the cases efficiently.

Reference genome

The reference genome used during the secondary analysis is required here. AION also determines the reference genome based on the content of the VCF files as part of the quality control process. In case there is conflict in the user input and AION’s deduced reference, the user is informed.

Upload files

In this section, you can upload all the VCF files to be analysed as part of this case. The sample and variant type need to be selected through the dropdown. Please keep in mind that, in the current implementation, AION will only process familial cases if both Mother and Father's VCF files are uploaded. Also, note that only small variants files are supported for the parents.

General info

Biological sex and DOB

You can optionally select one option (Female, Male, Not specified) and the DOB from the proband.

Currently, these values are exclusively used for your own case ID records and quality control.

Symptoms

Select as many symptoms/clinical features from the patient's clinical history and presentation as possible. Symptoms can be inputted by

• Searching for HPO terms and synonyms in the search bar

• Pasting HPO IDs into the input area (e.g. HP:0000002, HP:0000003...)

  

Once you have selected a symptom, AION will also provide a list of suggested related symptoms that might help refining the patient phenotype.

Gene and ACMG secondary findings filter

Users can choose to restrict the results to specific genes to focus on selected panels and/or to avoid secondary findings. Applying in silico panels effectively defines areas of interest within the supported regions.

To do so, AION enables filtering of specific genes in 3 different ways, which can be applied separately or in combination:

• Applying gene panels: select one or more gene panels, containing genes related a specific disease or health condition. Each condition has been curated into 4 different lists (Candidate Genes, Priority genes, Priority and Secondary genes, and Secondary genes) so that user can select the strength of the evidence backing up the relationship between genes and a specific condition.
  There are special panels also to exclude from the analysis the 78 genes whose variants are recommended to report as secondary findings by ACMG (Miller et al., Genetics in Medicine 2022), or to only focus on these 78 genes (search for “secondary findings” to apply them).

• Search genes: select individual genes.

• Paste genes: paste a las of genes separated by commas.

  

Parental information

In case of a trio analysis, fill the affectedness status of the parents.

Submitting the case

After filling in the case submission form, selecting "Run Analysis" will submit the case and start the process of data uploading, variant annotation, classification and ranking. You will be kept on upload screen while the data is being uploaded. After this, you are redirected to All cases and can continue working on other cases while the newly submitted case processes.

Once the analysis is done, a list of prioritized and classified variants for the submitted cases will show up in the All cases page. When a case shows a “View” button instead of processing status, you can open it to see the list of prioritized and classified variants.