From a3e568a8bd27b52f274658702f647729bab5768a Mon Sep 17 00:00:00 2001 From: Manuel Holtgrewe Date: Sat, 23 Dec 2023 17:39:13 +0100 Subject: [PATCH 1/3] docs: documenting ClinVar submission feature (#334) --- docs/doc_clinvarsub.rst | 157 ++++++++++++++++++++++++++++++++++++++++ docs/index.rst | 1 + 2 files changed, 158 insertions(+) create mode 100644 docs/doc_clinvarsub.rst diff --git a/docs/doc_clinvarsub.rst b/docs/doc_clinvarsub.rst new file mode 100644 index 00000000..8f15daf1 --- /dev/null +++ b/docs/doc_clinvarsub.rst @@ -0,0 +1,157 @@ +.. _doc_clinvarsub: + +================== +ClinVar Submission +================== + +This section describes the ClinVar submission feature of REEV. + +.. _doc_clinvarsub_prerequisites: + +------------- +Prerequisites +------------- + +To use this feature, you will need to fulfill the following prerequisites. + +1. You must have a ClinVar API key. + For this, you will first need to register your group with ClinVar and then request API access via an email to clinvar@ncbi.nlm.nih.gov. + You can find out more information `here about registering your organization with ClinVar `__ and `here about API keys `__. + +2. You need a REEV account. + This is easy, just click on "Login" on the top right of the REEV website. + The account will be enabled after logging in with one of the following options. + + As a member of a research organisation in the European Union, you can login via your home organisation using LifeScience Research Infrastructure (LSRI). + Otherwise, or if you prepare, you can login with OrcID. + OrcID is a free service that allows you to create a unique identifier for your publications, and you can also create an OrcID account by connecting your Google/Microsoft/... account. + + We chose these two options because we do not want to handle and store passwords and both LSRI/OrcID are secure login options and available to us without charge. + +Please note that the REEV authors are not affiliated with ClinVar, NCBI, or NIH. + +.. _doc_clinvarsub_overview: + +======== +Overview +======== + +Now that you have an account with REEV, access to a group account at ClinVar and your ClinVar API key (64 character long token), we can get started. +The overall process will be as follows: + +As a one-time setup, you will store the ClinVar API key in your REEV account. +Note that multiple people from the same group can do this and everything will still work. + +The process is then as follows: + +1. You enter the sequence or structural variant that you want to upload in to REEV and go to the page. + +2. You go to the "ClinVar Submission" tab and create a new submission. + +3. You send a create, update, or delete request to ClinVar by: + + a. Enter the required information (e.g., SCV accession for a deletion, or variant information for creation). + + b. Store this request on the REEV server which will put it into the work queue of REEV. + REEV will shortly submit this request to ClinVar. + + c. ClinVar will put your request into their work queue and process it eventually. + Note that this takes some time (in our experience 2 hours are not rare). + During this process, ClinVar will perform validation steps and may reject your request. + + The earlier that you get feedback from ClinVar, the higher the chance that there is a problem, so be patient. + Also see the section :ref:`doc_clinvarsub_commonerrors`. + After all automated validation steps are complete, you will get an SCV identifier and your submission will be published at the next release (usually the next Sunday). + No human validation is done on the side of ClinVar. + + Compared to the Excel submission, this process is a huge improvement even if it sounds complicated. + +.. _doc_clinvarsub_keysprofile: + +--------------------------- +ClinVar API Keys in Profile +--------------------------- + +TODO + +.. _doc_clinvarsub_deletion: + +---------------- +Variant Deletion +---------------- + +TODO + +.. _doc_clinvarsub_deletion_create: + +---------------- +Variant Creation +---------------- + +TODO + +.. _doc_clinvarsub_deletion_update: + +-------------- +Variant Update +-------------- + +TODO + +.. _doc_clinvarsub_commonerrors: + +------------- +Common Errors +------------- + +.. _doc_clinvarsub_commonerrors_recordisnotnovel: + +Record is not Novel +=================== + +Message + This record is submitted as novel but it should be submitted as an update, including the SCV accession, because your organization previously submitted for the same variant and condition. + +Explanation + Your organisation has already submitted a record with this “name” and condition (OMIM code or "not provided"). + ClinVar generates a variant name from your genomic coordinates. + Each organisation can only have one submission for the combination of the condition and variant. + +Resolution + You can either submit a revision of your interpretation, (or, e.g., extend the “observed in” information), or leave the record as it is. + +.. _doc_clinvarsub_commonerrors_namescannotbechanged: + +Submission Names Cannot be Changed +================================== + +Message + This update changes the description of the variant for , which is generally not allowed on a ClinVar record. + Please check the description of the variant and correct if necessary. + If you intend to change the description of the variant, please submit as a new record and delete this record. + Contact clinvar@ncbi.nlm.nih.gov if you have questions. + +Explanation + Most likely, you try to update the coordinates of a variant with an existing SCV. + ClinVar does not allow this. + Rather, you should remove the old variant and create a new submission. + +Resolution + Remove the old variant and add a new variant instead. + +.. _doc_clinvarsub_commonerrors_multipleconditions: + +Multiple Conditions have been submitted without explanation +=========================================================== + +Message + You provided multiple diseases as the condition for the classification. + If they represent related diseases along a spectrum, provide uncertain for multipleConditionExplanation. + If they represent diseases that occur together in an individual with the variant (this case is rare), provide co-occurring for multipleConditionExplanation.” + +Explanation + Multiple Condition IDs have been submitted for single variant. Check if this has been intentional. + If multiple conditions are to be submitted, a reason needs to be included with the submission. + +Resolution + Explicitly add either Uncertain, Co-occurring or Novel disease to the list of CONDITIONS. diff --git a/docs/index.rst b/docs/index.rst index df21cc82..c335b0e1 100644 --- a/docs/index.rst +++ b/docs/index.rst @@ -48,6 +48,7 @@ It provides the following features as a central resource: doc_queries doc_urls doc_manual + doc_clinvarsub .. toctree:: :hidden: From b6c67fc94259640b85cf778801ee7ffd2524e24f Mon Sep 17 00:00:00 2001 From: Manuel Holtgrewe Date: Sun, 24 Dec 2023 21:45:20 +0100 Subject: [PATCH 2/3] wip --- .gitignore | 2 + docs/doc_clinvarsub.rst | 91 ++++++++++++++++++--- docs/img/clinvarsub/clinvarsub-list.png | Bin 0 -> 41090 bytes docs/img/clinvarsub/clinvarsub-novel-1.png | Bin 0 -> 21254 bytes docs/img/clinvarsub/clinvarsub-novel-2.png | Bin 0 -> 81428 bytes docs/img/clinvarsub/clinvarsub-novel-3.png | Bin 0 -> 118293 bytes docs/img/clinvarsub/clinvarsub-novel-4.png | Bin 0 -> 96521 bytes docs/img/clinvarsub/clinvarsub-novel-5.png | Bin 0 -> 45041 bytes docs/img/clinvarsub/org-editor.png | Bin 0 -> 20444 bytes docs/img/clinvarsub/org-list-empty.png | Bin 0 -> 28285 bytes 10 files changed, 81 insertions(+), 12 deletions(-) create mode 100644 docs/img/clinvarsub/clinvarsub-list.png create mode 100644 docs/img/clinvarsub/clinvarsub-novel-1.png create mode 100644 docs/img/clinvarsub/clinvarsub-novel-2.png create mode 100644 docs/img/clinvarsub/clinvarsub-novel-3.png create mode 100644 docs/img/clinvarsub/clinvarsub-novel-4.png create mode 100644 docs/img/clinvarsub/clinvarsub-novel-5.png create mode 100644 docs/img/clinvarsub/org-editor.png create mode 100644 docs/img/clinvarsub/org-list-empty.png diff --git a/.gitignore b/.gitignore index 45f332ed..dd2ae130 100644 --- a/.gitignore +++ b/.gitignore @@ -1,3 +1,5 @@ +*:Zone.Identifier + # Root Pipfile /Pipfile /Pipfile.lock diff --git a/docs/doc_clinvarsub.rst b/docs/doc_clinvarsub.rst index 8f15daf1..23f7b0e2 100644 --- a/docs/doc_clinvarsub.rst +++ b/docs/doc_clinvarsub.rst @@ -72,25 +72,84 @@ The process is then as follows: ClinVar API Keys in Profile --------------------------- -TODO +After logging in, click "Profile" on the top right of the REEV website. +Then, select "Orgs / Keys" menu on the left below "ClinVar Submissions". +You will be shown the following screen. +Here, you can find all of your organisations for which you have stored an API key in REEV. +Most users, will not have more than one entry here. -.. _doc_clinvarsub_deletion: +.. figure:: img/clinvarsub/org-list-empty.png + :align: center ----------------- -Variant Deletion ----------------- +To create a new entry, click on the green "New" button on the top right. +A modal will be shown where you can register a new organisation. +You have to provide a label (only used for display purposes) and the ClinVar API key. +Click "Create" to store the new entry. -TODO +.. figure:: img/clinvarsub/org-editor.png + :width: 50% + :align: center -.. _doc_clinvarsub_deletion_create: +You now have successfully registered your ClinVar API key and can start create submissions. ----------------- -Variant Creation ----------------- +.. _doc_clinvarsub_variant_novel: -TODO +------------------- +Submit Novel Record +------------------- + +Submitting a *novel* record means that a given variant has not been submitted to ClinVar before. +In this case, simply navigate to the given sequence or structural variant in REEV. +Click "ClinVar Submission" in the navigation or scroll down to the corresponding box. + +.. figure:: img/clinvarsub/clinvarsub-novel-1.png + :width: 50% + :align: center + +Here, click the "Create Submission" button. +A step by step wizard will guide you through the process. +First, select the organisation for which you want to submit the record. +The screenshots below show the prcoess for sequence variants but the process is the same for structural variants. +Here, we focus on new submissions, in :ref:`doc_clinvarsub_variant_update` we will discuss updates and in :ref:`doc_clinvarsub_variant_delete` we will discuss deletions. +Click "Next". + +.. figure:: img/clinvarsub/clinvarsub-novel-2.png + :width: 50% + :align: center + +On the next screen, you can enter the information that you want to submit. +The most important fields are the clinical significance and the condition. +Also, you might want to assign some HPO phenotype terms of your patient. +When you are done, click "Next". + +.. figure:: img/clinvarsub/clinvarsub-novel-3.png + :width: 50% + :align: center -.. _doc_clinvarsub_deletion_update: +In this screen, you can review your submission. +In the case that you want to adjust something, click "previous" to go back. +Otherwise, click "submit creation request" to start the submission. +By this, you create a submission job in REEV and a request will be sent to ClinVar. + +.. figure:: img/clinvarsub/clinvarsub-novel-4.png + :width: 50% + :align: center + +This job will be shown in the following overview table. +It can take some time for ClinVar to process your request, and updates will be shown in the table below. + +.. figure:: img/clinvarsub/clinvarsub-novel-5.png + :width: 50% + :align: center + +You can also go to your profile and the click "Submission Activity" on the left. +You can see all of your past and current submission activity. + +.. figure:: img/clinvarsub/clinvarsub-list.png + :width: 50% + :align: center + +.. _doc_clinvarsub_variant_update: -------------- Variant Update @@ -98,6 +157,14 @@ Variant Update TODO +.. _doc_clinvarsub_variant_delete: + +---------------- +Variant Deletion +---------------- + +TODO + .. _doc_clinvarsub_commonerrors: ------------- diff --git a/docs/img/clinvarsub/clinvarsub-list.png b/docs/img/clinvarsub/clinvarsub-list.png new file mode 100644 index 0000000000000000000000000000000000000000..54f862b8b927d74396e58b294cd7cc9cee770288 GIT binary patch literal 41090 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character long token), we can get started. The overall process will be as follows: @@ -155,7 +155,9 @@ You can see all of your past and current submission activity. Variant Update -------------- -TODO +Variant updates work the same as variant creations. +However, in the first step you have to enable "I want to update/delete an existing submission and I have an SCV", enter the SCV accession, and keep the third switch as "Update Variant". +Note that you will currently have to re-fill the data in the "Enter Data" step. .. _doc_clinvarsub_variant_delete: @@ -163,7 +165,9 @@ TODO Variant Deletion ---------------- -TODO +Deleting a submission is even simpler. +In the first step, check "I want to update/delete an existing submission and I have an SCV", enter the SCV accession, and change the third switch to "Delete Variant". +You can optionally provide a free-text reason for removing the variant submission. .. _doc_clinvarsub_commonerrors: @@ -171,6 +175,21 @@ TODO Common Errors ------------- +.. _doc_clinvarsub_commonerrors_invalidapikey: + +Invalid API Key +=============== + +Message + No valid API key provided. + +Explanation + The API key that you provided is not valid. + Please check that you have entered the correct key. + +Resolution + Correct the value that you provided in the REEV profile. + .. _doc_clinvarsub_commonerrors_recordisnotnovel: Record is not Novel