NHS North West Genomics
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Distributed Whole Genome Sequencing (dWGS)

References

  1. Inter-Laboratory Workflow (ILW) - Sub-orders LAB-35 and LAB-36
  2. laboratory-order MessageDefinition
  3. HL7 v2 Standards
  4. NHS England RGL to SGL SOP (37-field national digital manifest, Appendix 3) - referenced by name only, not publicly linked

Clinical Pathway Overview

What is being tested

Whole Genome Sequencing (WGS) is used to look for the genetic cause of a suspected rare or inherited condition. Rather than testing one gene at a time, WGS reads a patient's entire genome, so it can find variants anywhere - useful when the clinical picture doesn't point to one specific gene, or when a targeted test has already come back negative. Testing one or more close relatives alongside the patient (the Proband) makes it much easier to tell which variants are relevant:

Family Structure Clinical purpose
Singleton Used when relatives' samples aren't available, or aren't expected to help interpretation
Duo Comparing against one relative (usually a parent) narrows down candidate variants
Trio Comparing against both biological parents can directly identify a de novo (new, not inherited) variant - the strongest design for rare/inherited disease

The end-to-end clinical journey

  1. Patient identified - a clinician suspects a rare or inherited genetic condition and decides WGS is the right test, including whether parental/relative samples should be tested alongside the patient.
  2. Samples taken - a blood/DNA sample is taken from the patient (proband) and, for a Duo or Trio, from the relevant relatives too.
  3. Referral submitted - the Requesting Genomic Laboratory (RGL) submits the sample(s) and a digital manifest to whichever Sequencing Genomic Laboratory (SGL) is doing the sequencing - which may be a different region's laboratory. (This is the LAB-35 sub-order in the technical process below.)
  4. Sequencing performed - the SGL sequences the sample(s) and returns the result to the RGL. (LAB-36.)
  5. Report issued - the RGL's report reaches the original ordering clinician. (LAB-3/LAB-5.)
  6. Clinical decision - the clinical/genetics team interprets any variants found, discusses the result with the patient and family, and may refer relatives for genetic counselling or cascade testing.
flowchart LR
    A[Patient/family<br/>identified for WGS] --> B[Samples taken -<br/>proband +/- relatives]
    B --> C[Referral to SGL<br/>for sequencing]
    C --> D[Sequencing<br/>performed]
    D --> E[Report reaches<br/>ordering clinician]
    E --> F[Clinical review -<br/>may lead to genetic<br/>counselling referral]

Why this matters for developers

  • Family Structure/Participant Type are what distinguish a Singleton, Duo or Trio referral - see Singleton, Duo and Trio testing below for how these are represented.
  • Each participant is submitted as their own separate sub-order (own Patient, Specimen, ServiceRequest) - not combined into one message - linked together only by a shared requisition number.
  • Family Structure/Participant Type are asked at order entry precisely so the SGL knows, before sequencing starts, how many samples to expect for one referral and how to interpret them together.

Actors

IHE Actor (ILW) Role in dWGS System (worked examples)
Order Placer Test Ordering Entity - NHS Trust sending the initial LAB-1 order, upstream of this sub-order NHS Trust EPR
Requestor (Order Placer) Requesting Genomic Laboratory (RGL) NE&Y Genomics
Subcontractor (Order Filler) Sequencing Genomic Laboratory (SGL) NW Genomics (iGene)

Transactions

Transaction Description Direction
LAB-1 Laboratory Order (original clinical order, upstream of this sub-order) - see GMS WGS Rare Disease (Rare Disease pathway) and GMS WGS Cancer (Cancer pathway) Test Ordering Entity → RGL
LAB-35 Sub-order Management (sample + digital manifest) RGL → SGL
LAB-36 Sub-order Results Delivery (sequencing result) SGL → RGL
LAB-3 / LAB-5 Laboratory Report (downstream of this sub-order) RGL → Test Ordering Entity

Current Process

Whole Genome Sequencing (WGS) for rare and inherited disease is being moved by NHS England from a single centralised laboratory to a distributed model (dWGS): each NHS Genomic Medicine Service (GMS) geography's own laboratory acts as a Requesting Genomic Laboratory (RGL), submitting DNA samples and a digital manifest directly to whichever laboratory is acting as Sequencing Genomic Laboratory (SGL) for that sample - which may be another GMS's laboratory rather than the RGL's own.

The LAB-1 leg upstream of this - the Test Ordering Entity (Order Placer) raising the original clinical order with the RGL (Order Filler) - uses one of the two national GMS WGS forms, depending on pathway:

  • Rare Disease: GMS WGS Rare Disease - In the North East & Yorkshire NE&Y Genomics is the RGL, in the North West NW Genomics is the RLS and NW Genomics is the SGL for both.
  • Cancer: GMS WGS Cancer - In the North West: NW Genomics is the RGL and Royal Marsden is the SGL

Results/data returning to the RGL for analysis and reporting are handled by Genomics England Limited (GEL), using referral_id and patient_ngis_id as the identifiers - these are the only identifiers present across every system in this workflow (RGL LIMS, TOMS, SGL LIMS, GEL).

While NW Genomics is the SGL for NE&Y dWGS, the vast majority of NE&Y's results go back to NE&Y directly (LAB-5 and LAB-36 returning to the RGL) and are reported (LAB-3) by NE&Y, not via NW Genomics. The integration NW Genomics needs to build for this workflow is therefore one direction only - LAB-35.

Where the RGL and SGL are different organisations, this is a sub-contracted order: in NW-GMSA's own Inter-Laboratory Workflow (ILW) terms, the RGL is the Order Placer sending a LAB-35 sub-order to the SGL (the Order Filler), with the sequencing result returned as LAB-36. That sub-order can be sent as either a FHIR Bundle (POST [base]/$process-message, the laboratory-order MessageDefinition) or HL7 v2 OML^O21 (see HL7 v2 Standards) - both follow the same underlying NW-GMSA order model, so the choice is purely about what the sending system can produce.

The diagram below shows the entire background process end-to-end - Test Ordering Entity through to Automation Manager - for context only. This page itself elaborates just the LAB-35/LAB-36 sub-order in the middle; the legs either side of it are covered elsewhere:

  • LAB-1/LAB-3 (Test Ordering Entity ↔ RGL) - the general shape of this leg is documented in Regional Orders and Reports. For NE&Y Genomics specifically (acting as RGL here), the current, live data contract already used with them is documented in NE&Y Management Information (ctDNA) - important to this use case, since this leg should ideally continue to align with that established contract rather than diverge from it.
  • LAB-4/LAB-5 (SGL ↔ Automation Manager) - background only; see OMICS DSS Result Integration for that leg's own detail. NW Genomics' Automation Manager role here is currently DLIMS, which Clarity LIMS will likely replace - see this page's own Outstanding Issues above.
flowchart TD
  OP["Order Placer<br/>Test Ordering Entity"]
  OF["Order Filler<br/>Requesting Genomic Laboratory (RGL)"]
  SC["Sub Contractor<br/>Sequencing Genomic Laboratory (SGL)"]
  ANP["Automation Manager<br/>Analyser and<br/>Analytics Processor"]

  OP -- "LAB-1<br/>laboratory order" --> OF
  OF -- "LAB-35<br/>sub-order + manifest" --> SC
  SC -- "LAB-36<br/>sequencing result" --> OF
  OF -- "LAB-3<br/>laboratory report" --> OP
  SC -- "LAB-4<br/>Work Order" --> ANP
  ANP -- "LAB-5<br/>Test Result and Reportable Variant" --> SC

sequenceDiagram
    participant OP as Order Placer<br/>Test Ordering Entity
    participant OF as Order Filler<br/>RGL
    participant TOMS as TOMS<br/>(Test Order Management System,<br/>Genomics England Limited)
    participant SC as Sub Contractor<br/>SGL
    participant ANP as Automation Manager<br/>Analyser/Analytics Processor

    Note over OP,OF: NW Genomics only - covers both <br/>electronic and paper LAB-1 orders.
    OP ->> OF: LAB-1 Laboratory Order
  Note over OF,SC: Enter LAB-1 order (TOMS) applies to<br/>both NW Genomics and NE&Y Genomics

  OF ->> TOMS: Enter LAB-1 order
    TOMS ->> OF: referral_id, patient_ngis_id
    OF ->> SC: LAB-35 Sub-order + manifest
    SC ->> ANP: LAB-4 Work Order
    Note over ANP,OP: LAB-5 onwards - out of scope for NW-GMSA,<br/>handled by GEL and NE&Y
    ANP ->> SC: LAB-5 Test Result and Reportable Variant
    SC ->> OF: LAB-36 Sequencing Result
    Note over OF,OP: NW-GMSA only - the LAB-3 report may instead be<br/>sourced via NHS England's UGR or GOMS
    OF ->> OP: LAB-3 Laboratory Report

Singleton, Duo and Trio testing

A WGS referral tests one or more people together as a single family group, so that variants found in the person affected by the suspected condition (the Proband) can be interpreted in the context of their close relatives. NW-GMSA's dWGS examples use two "ask at order" data items to describe this, carried as Observation resources referenced from ServiceRequest.supportingInfo:

  • Family Structure - how many people are being tested together as part of this referral: Singleton, Duo or Trio.
  • Participant Type - this individual's role within that family structure: Proband or Family Member.
Family Structure Participants tested Typical use
Singleton Proband only No parental samples available, or a family structure isn't expected to aid interpretation
Duo Proband + one Family Member (usually a parent) Narrows candidate variants by comparing against one relative
Trio Proband + two Family Members (usually both parents) The strongest common design for rare/inherited disease - directly identifies de novo (new, not inherited) variants by comparing the Proband against both biological parents

Each participant in a Duo or Trio is sequenced and submitted as their own separate sub-order (their own Patient, Specimen and ServiceRequest, each with their own NGIS participant identifier), not combined into one message. What ties the participants of the same referral together is a shared referral/requisition number (ServiceRequest.requisition), assigned by the RGL - every sub-order from the same family structure carries the same requisition value, distinguished by each participant's own identifier.

Each example also demonstrates identifying the specimen container separately from the specimen itself, using the local ZCID "Container Identifier" code from NW IdentifierType on Specimen.container.identifier.type

  • see the Container Identifier note on the HL7 v2 SPM segment page for why this is only needed as a type code on the HL7 v2 side.

Future Process

No distinct future-state changes are currently defined for this pathway beyond what RGL to SGL SOP v0.4 and the worked examples above already describe - this section will be populated as NHS England's national dWGS rollout matures.

Data Models

Ask at Order Entry: the dWGS digital manifest

A LAB-35 sub-order like the worked examples above is built from a digital manifest: NHS England's RGL to SGL SOP defines 37 national manifest fields (Appendix 3), and a Requesting Genomic Laboratory may add further local-extension fields for the Sequencing Genomic Laboratory's benefit - the worked examples on this page add 5. This IG models the manifest as two separate Questionnaires, not one:

  • dWGS Sub-Order Manifest - a CSV manifest description, not an Ask At Order Entry Questionnaire. It documents all 42 fields the RGL actually sends, including several also asked by the core Genomic Test Order form (Patient name/DOB/NHS number, Specimen Type, Specimen Collection Date) - correctly, since it describes the complete manifest structure rather than an incremental set of order-entry questions layered on top of the core form.
  • dWGS Ask At Order Entry Questions - the genuinely additional questions, derivedFrom/extending Genomic Test Order the same way every other Ask At Order Entry Questionnaire does (see Order Entry Questions). It carries every manifest field except the six that duplicate the common core exactly - see Field mapping below for which is which, and Outstanding Issues below for a remaining question about where some of these fields originate.

The two fields specific to dWGS - Family Structure and Participant Type (see Singleton, Duo and Trio testing above) - are dWGS Ask At Order Entry Questions' main Ask at Order Entry questions: enumerated-string answers with no NW-GMSA-confirmed coding system, carried as Observation.valueCodeableConcept (text only) referenced from ServiceRequest.supportingInfo. Unlike Genetic Clinical Referral - Consultand, which references a second individual (the consultand) from the proband's own ServiceRequest, a Duo or Trio's Family Member is not referenced from the Proband's sub-order at all - each participant (Proband and every Family Member) is submitted as their own completely separate sub-order, tied together only by a shared requisition number (see The end-to-end clinical journey above). There is no equivalent here to Consultand's RelatedPerson/ServiceRequest.supportingInfo cross-reference - see WGS Local Test Order for a closer relative that does use that pattern.

Field mapping: CSV → HL7 v2 → FHIR

The table below is the full 42-field mapping (37 national fields plus 5 local extension fields). The Modelled In column shows which Questionnaire(s) each field appears in: every field is part of dWGS Sub-Order Manifest (the complete manifest description); most are also part of dWGS Ask At Order Entry, except the six marked Genomic Test Order (base), which duplicate a common-core item exactly (same linkId and code) and so are asked once, by the core form, rather than repeated in the Ask At Order Entry Questionnaire. Where the FHIR Field column is blank, the field is carried in the manifest but has no confirmed FHIR mapping yet - a genuine open question for a future pass, not an oversight.

CSV Field Common Name Cardinality Type HL7 v2 Field FHIR Field Modelled In
referral_id Original Order Placer Group Number MUST String OBX-5 (OBX-3=NGIS_REFERRAL_ID) ServiceRequest.requisition dWGS Ask At Order Entry
clinical_indication_test_type_id Test Code OPTIONAL String OBR-4.1 ServiceRequest.code.coding (England-GenomicTestDirectory) dWGS Ask At Order Entry
patient_nhs_number NHS Number OPTIONAL String PID-3 (NH) Patient.identifier (NHS number) Genomic Test Order (base)
patient_ngis_id Patient Identifier MUST String PID-3 (NGIS) Patient.identifier.assigner (Genomics England, ODS 8J834) dWGS Ask At Order Entry
patient_date_of_birth Date Of Birth OPTIONAL Date PID-7.1 Patient.birthDate Genomic Test Order (base)
ordering_entity_id Original Ordering Facility Code OPTIONAL Code (ODS Code) ORC-21 Specimen.identifier (as received) assigner dWGS Ask At Order Entry
glh_laboratory_id Filler Order Ordering Facility Code MUST Code (ODS Code) ORC-21 ServiceRequest.requester / requisition assigner / Specimen.identifier (LIMS) assigner dWGS Ask At Order Entry
primary_sample_received_date Sample Received Date OPTIONAL Date SPM-18 (primary SPM) Specimen.receivedTime (primary specimen) dWGS Ask At Order Entry
primary_sample_id_as_received_by_glh Received Sample Identifier OPTIONAL String SPM-2.1 (primary SPM) Specimen.identifier (as received) dWGS Ask At Order Entry
primary_sample_id_in_glh_lims LIMS Sample Identifier OPTIONAL String SPM-2.2 (primary SPM) Specimen.identifier (GLH LIMS) dWGS Ask At Order Entry
primary_sample_type Sample Type MUST Code (Specimen Type SNOMED CT) SPM-11 (primary SPM, low confidence) Specimen.type / extension (germline vs tumour, low confidence) dWGS Ask At Order Entry
primary_sample_state Sample Material Type MUST Code (Specimen Type SNOMED CT) SPM-4.1 (primary SPM) Specimen.type (SNOMED CT coding) Genomic Test Order (base)
received_sample_topography Sample Topography MUST (cancer only) String SPM-8 (primary SPM, cancer only) Specimen.bodySite (cancer only) dWGS Ask At Order Entry
received_sample_morphology Sample Morphology OPTIONAL String - - dWGS Ask At Order Entry
received_sample_tumour_content_% Tumour Content MUST (cancer only) Number - - dWGS Ask At Order Entry
received_sample_comments Sample Comments OPTIONAL String - - dWGS Ask At Order Entry
received_sample_collection_date Specimen Collection Date OPTIONAL Date SPM-17 Specimen.collection.collectedDateTime Genomic Test Order (base)
dispatched_sample_id_in_glh_lims Dispatched Sample Identifier OPTIONAL String - - dWGS Ask At Order Entry
dispatched_sample_lsid Specimen Barcode MUST String SPM-2.1 (type=ZCID) and OBX-5 (OBX-3=DISPATCHED_SAMPLE_LSID) Specimen.container.identifier dWGS Ask At Order Entry
dispatched_sample_type Dispatched Sample Type MUST Code (Specimen Type SNOMED CT) - - dWGS Ask At Order Entry
dispatched_sample_state Dispatched Material Type MUST Code (Specimen Type SNOMED CT) SPM-4.1 (dispatched SPM, not built in this worked example) Specimen.type (not built - single Specimen only carries primary_sample_state) dWGS Ask At Order Entry
dispatched_sample_volume_(ul) Sample Volume OPTIONAL Number SPM-12 Specimen.collection.quantity dWGS Ask At Order Entry
laboratory_remaining_volume_banked_(ul) Remaining Banked Volume OPTIONAL Number - - dWGS Ask At Order Entry
glh_concentration_(ng/ul) DNA Concentration OPTIONAL Number - - dWGS Ask At Order Entry
glh_od260/280 DNA Purity OPTIONAL Number - - dWGS Ask At Order Entry
glh_din_value DNA Integrity Number OPTIONAL Number - - dWGS Ask At Order Entry
glh_percentage_DNA_over_23kb DNA Fragment Size OPTIONAL Number - - dWGS Ask At Order Entry
glh_qc_status QC Status OPTIONAL String - - dWGS Ask At Order Entry
glh_sample_dispatch_date Dispatch Date OPTIONAL Date - - dWGS Ask At Order Entry
glh_sample_consignment_number Consignment Number OPTIONAL String SPM-32 Specimen.identifier (type=STN) dWGS Ask At Order Entry
plating_organisation Plating Organisation OPTIONAL Enum - - dWGS Ask At Order Entry
gmc_rack_id Rack Identifier OPTIONAL String - - dWGS Ask At Order Entry
gmc_rack_well Rack Well Position OPTIONAL String (pattern) - - dWGS Ask At Order Entry
dna_extraction_protocol DNA Extraction Method OPTIONAL String SPM-7 Specimen.collection.method dWGS Ask At Order Entry
prolonged_sample_storage Sample Storage Method OPTIONAL String - - dWGS Ask At Order Entry
retrospective_sample Retrospective Sample Flag OPTIONAL Enum (no clean v2 field) ServiceRequest.intent (reflex-order when Retrospective) dWGS Ask At Order Entry
approved_by Approved By OPTIONAL String - - dWGS Ask At Order Entry
patient_forename Forename MUST String PID-5.2 Patient.name.given Genomic Test Order (base)
patient_surname Surname MUST String PID-5.1 Patient.name.family Genomic Test Order (base)
family_structure Family Structure MUST Enumerated string OBX-5 (OBX-3=FAMILY_STRUCTURE) Observation (via ServiceRequest.supportingInfo) dWGS Ask At Order Entry
participant_type Participant Type MUST Enumerated string OBX-5 (OBX-3=PARTICIPANT_TYPE) Observation (via ServiceRequest.supportingInfo) dWGS Ask At Order Entry
clinical_information Clinical Information OPTIONAL String NTE-3 ServiceRequest.note dWGS Ask At Order Entry

Two specimens, not one: primary_sample_* fields describe the specimen as originally received at the GLH (blood/tissue, before extraction); dispatched_sample_* describes the extracted DNA sent onward. The worked examples below carry both as identifiers/values on a single Specimen resource rather than two linked resources.

Outstanding Issues

Partially resolved. Some of the manifest fields described above originate from Genomics England's own centralised WGS systems, rather than being fields NW-GMSA itself asked for. Confirmed: the RGL enters the LAB-1 order into TOMS (Test Order Management System, Genomics England Limited) - see the Current Process sequence diagram above - and TOMS returns referral_id and patient_ngis_id in response, rather than either being minted by the RGL itself. This is a Genomics England system, entered from the paper GMS WGS Rare Disease and GMS WGS Cancer national order forms, and the two identifiers it returns are then carried over into the dWGS digital manifest along with the rest of the sub-order:

  • referral_id ("Original Order Placer Group Number (Referral ID)", dWGS/referral_id, ServiceRequest.requisition) reads like a Genomics England OrderFillerGroupNumber-style concept, not the OrderPlacerNumber + OrderPlacerGroupNumber pair this IG would typically expect a Requesting Genomic Laboratory to assign for its own referral (see Genomic Test Order - Diagnostic Workflow).
  • patient_ngis_id ("Patient Identifier (NGIS)", Patient.identifier, assigned by Genomics England, ODS 8J834) reads like a Genomics England PatientAccessionIdentifier-style concept, not the MedicalRecordNumber this IG would typically expect (see NHS Identifier).

Neither national paper form captures a referral_id/patient_ngis_id equivalent itself - both are silent on Order Placer Number and Medical Record Number too (see their own Summary sections) - which is consistent with these values being minted downstream by TOMS, once the RGL enters the LAB-1 order into it, rather than by the Requesting Genomic Laboratory at the point of ordering. What remains open is the detail of that TOMS interaction itself - e.g. whether it is a synchronous API call an RGL's own system makes as part of order entry, or a manual/batch step - which isn't yet documented for this IG.

Which internal system NW Genomics (iGene) actually uses to perform the sequencing behind its Sequencing Genomic Laboratory (SGL) role is not documented on this page. Actors above treats NW Genomics as a single black box that "performs the test" (LAB-35/LAB-36), without naming an internal pipeline the way OMICS DSS Result Integration does for DLIMS/Omics DSS. It's possible dWGS sequencing runs through that same DLIMS/Omics DSS pipeline (and so would eventually be affected by Clarity LIMS if that replaces it), or through a separate pipeline entirely - WGS is a different scale of sequencing from the "cancer or rare disease gene panel" examples OMICS DSS Result Integration - What is being tested gives for DLIMS, so the two aren't necessarily the same underlying lab operation. Not confirmed either way - see the matching note on Clarity LIMS - Outstanding Issues.

Examples

The dWGS example Bundles cover one referral of each family structure, sent as LAB-35 sub-orders from a Requesting Genomic Laboratory to NW Genomics acting as Sequencing Genomic Laboratory:

Referral Family Structure Participants
r2026000201 Singleton Proband (p2026000101) - Bundle-dWGS-Singleton-r2026000201
r2026000202 Duo Proband (p2026000102) - Bundle-dWGS-Duo-r2026000202-p2026000102
Family Member (p2026000103) - Bundle-dWGS-Duo-r2026000202-p2026000103
r2026000203 Trio Proband (p2026000104) - Bundle-dWGS-Trio-r2026000203-p2026000104
Family Member (p2026000105) - Bundle-dWGS-Trio-r2026000203-p2026000105
Family Member (p2026000106) - Bundle-dWGS-Trio-r2026000203-p2026000106

Each row of the source manifest (Input/dWGS.csv) gives one referral participant, shown below in three forms: the QuestionnaireResponse answering dWGS Sub-Order Manifest, the LAB-35 sub-order Bundle it was extracted into (same referrals and participants as the table above), and the HL7 v2 OML^O21 equivalent of that same Bundle (from nw-gmsa/Testing):

Referral Participant QuestionnaireResponse FHIR Laboratory Order Message HL7 v2 Example
r2026000201 Proband (p2026000101) QuestionnaireResponse-dWGS-Singleton-r2026000201-p2026000101 Bundle-dWGS-Singleton-r2026000201 dWGS_r2026000201.txt
r2026000202 Proband (p2026000102) QuestionnaireResponse-dWGS-Duo-r2026000202-p2026000102 Bundle-dWGS-Duo-r2026000202-p2026000102 dWGS_r2026000202_p2026000102.txt
r2026000202 Family Member (p2026000103) QuestionnaireResponse-dWGS-Duo-r2026000202-p2026000103 Bundle-dWGS-Duo-r2026000202-p2026000103 dWGS_r2026000202_p2026000103.txt
r2026000203 Proband (p2026000104) QuestionnaireResponse-dWGS-Trio-r2026000203-p2026000104 Bundle-dWGS-Trio-r2026000203-p2026000104 dWGS_r2026000203_p2026000104.txt
r2026000203 Family Member (p2026000105) QuestionnaireResponse-dWGS-Trio-r2026000203-p2026000105 Bundle-dWGS-Trio-r2026000203-p2026000105 dWGS_r2026000203_p2026000105.txt
r2026000203 Family Member (p2026000106) QuestionnaireResponse-dWGS-Trio-r2026000203-p2026000106 Bundle-dWGS-Trio-r2026000203-p2026000106 dWGS_r2026000203_p2026000106.txt

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