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I want to find a diagnosis for patients who didn't get one through primary clinical interpretation

How to use this page

Below you can switch between three categories: no code, pre-run algorithms and from scratch. Please select the version that matches your skills and the scale of the task you want to do.

Category Scale Skills needed Overview Audience
no code small basic IT skills Uses no code tools in the RE Clinicians and biologists without coding or command line skills
pre-run algorithms small basic IT skills uses data generated in-house Clinicians and biologists without coding or command line skills
from scratch large command line, coding and common bioinformatics tools illustrates the steps you might follow using common bioinformatics tools to carry out custom analyses bioinformaticians/computational biologists doing custom analyses

The instructions in each section include links to the relevant pages in the documentation. Links are tagged as:

  • Tutorials
  • Tools - descriptive
  • Data - descriptive
  • Pre-made workflows
  • Reference lists/tables

Identify participant(s)

You can identify participants of interest using either LabKey or Participant Explorer. These will usually be participants where the case is not listed as solved in the gmc_exit_questionnaire, and often participants who are still alive.

Filter variants in participant(s)

You can identify variants in your participant of interest in the IVA Case portal.

You can filter by mode of inheritance, by variant population frequency, by variant consequences on genes and other factors. You can also filter by gene lists from PanelApp.

Identify participant(s)

You can identify participants of interest using either LabKey or Participant Explorer. These will usually be participants where the case is not listed as solved, and often participants who are still alive.

View tiered and exomiser variants

We have run tiering analysis and Exomiser on all rare disease participants to identify potentially causal variants.

Identify participant(s)

You can identify participants of interest using the LabKey API. These will usually be participants where the case is not listed as solved, and often participants who are still alive. You can create a list of gVCF or BAM filepaths. We also have a tutorial on cohort building to work through:

Working with the HPC

Tools such as Exomiser and VEP are available on the HPC and can be incorporated into your own algorithms and pipelines for analysing genomes, or you can write these from scratch.

Create or import pipelines

You can use any programming languages that are provided on the HPC. We also provide conda environments for working in Python and R libraries.

If you have your own pipelines written as containers, you can use Singularity to bring them into the RE.

Validate variants

You may wish to validate any variants you have identified in IGV. To do this you will need to get the BAM file locations for the participant and their family members, which you can do from the file locations in Participant Explorer. You can upload these files to view in IGV.

You may wish to work with some tools outside of the RE to see what other data has been associated with your variants of interest, such as gnomAD, Decipher, ClinVAR and Varsome.

Compile text and figures

You can use LO Calc to create figures and tables. You can also write any notes in LO Writer.

Export

If you think you have identified potentially diagnostic genetic variants and you would like to report these back to the GMS, or to get in contact with the clinical team to carry out further tests, you can get in contact using a form available through Airlock.