Methodology
How the edition was made: methods, the model card, the evidence cut and its age, the acceptance record and the glossary.
Contents
- ·Edition home
- ·Executive summary
- 1Genomics is data infrastructure and a therapeutic frontier
- 2Key findings
- 3Systems and sectors at baseline
- 4Risks and capability
- 5Individualised editing outpaces delivery systems
- 6Readings from the other desks
- 7The 2027 agenda
- 8Systems in depth
- AMethodology
- BData appendix
- CReferences and record
- ·Complete edition, for print
A.1Methods
The global baseline uses published values and four simple derivations. Each is shown in full so that any reader can reproduce it.
| No. | Derivation | Calculation | Result |
|---|---|---|---|
| (1) | Share of evaluable sickle cell patients free of crises | 29 ÷ 30 | 97% |
| (2) | Share of evaluable thalassaemia patients transfusion independent | 32 ÷ 35 | 91% |
| (3) | Year-on-year growth in Casgevy revenue, first quarter | 42.9 ÷ 14.2 | about 3.0 times |
| (4) | Evaluable share of treated sickle cell patients | 30 ÷ 44 | 68% |
| Strength | Definition |
|---|---|
| STRONG | a disruption in the source system has historically changed the target system’s service or output within one season, in more than one region |
| MODERATE | an effect is documented but buffered or slower |
| WEAK | an effect is plausible but not documented at global scale |
| Label | Rule |
|---|---|
| Reported | value as issued by its source, with year |
| Inferred | reasoned from cited evidence; never a measurement |
| Estimated | Nexus analytical value with stated method |
| Scenario | conditional on stated assumptions |
| Expert input | structured editorial judgement awaiting evidence |
A.2Model card, Genomics System Model v0
- Model ID
- MDL-XT05-GENOMICS · v0.1
- Purpose
- represent genomics and gene editing as infrastructure coupled to health, compute and energy, trade and supply, finance, workforce and data protection
- Family
- graph-based system of systems
- Inputs
- the cited sources of this edition; no proprietary data
- Method
- expert-specified coupling strengths (STRONG · MODERATE · WEAK) from assessments and analogue events
- Validation
- none yet, first validation against federation evidence in 2027
- Uncertainty
- qualitative; strengths are hypotheses, not measurements
- Domain of validity
- global scale; not for asset-, site- or country-level use
- Reproducibility
- strength table and sources published in this edition
20couplings
typed in v0
0strong
documented within one season
3moderate
documented, buffered
17weak
plausible, undocumented
A.3The baseline evidence cut
Every Nexus edition is published from a frozen evidence cut. The global baseline cut is documentary: it pins the exact edition of every source cited. Federation cuts begin with the first national Foundry cuts in 2027.
- Cut ID
- DC-XTECH-GENOMICS-GLOBAL-2026-B0
- Type
- baseline documentary cut
- Resolution policy
- pinned · as of 30 September 2026
- Sources pinned
- 44 cited sources, each at the edition and access date in the references
- Model runs
- none at baseline, analytical values are stated with their method
- Digest
- computed at freeze and recorded in the publication record
- Supersedes
- nothing, first cut of the series
- Superseded by
- the 2027 genomics annual cut
Lineage
- 01
source edition
- 02
pinned citation
- 03
finding
- 04
page
- 05
publication record
| Element | Baseline 2026 | 2027 global annual |
|---|---|---|
| Sources | cited global publications, pinned by edition | national, regional and sector cuts through one graph |
| Analysis | stated methods and editorial estimates | typed analysis specifications |
| Models | Genomics System Model v0 specification | model runs with receipts |
| Findings | twelve baseline findings | findings re-bound to federation evidence |
| Review | five passes scheduled | five passes on the exact digest |
A.4Evidence age and coverage
A 2026 global edition rests on evidence observed in many different years. This page shows each time base, so that no single year label hides older evidence.
| Indicator | Observed | Released | Cadence | Next release |
|---|---|---|---|---|
| Phase 3 sickle cell and thalassaemia reports | 2024 | NEJM 2024 | one-off | longer follow-up |
| FDA approval | 2023 | Dec 2023 | one-off | paediatric label |
| Patient-specific base editing report | 2025 | NEJM 2025 | one-off | follow-up |
| Reference genome and pangenome | 2022 to 2023 | Science 2022 · Nature 2023 | periodic | pangenome release 2 |
| Biobank genome releases | 2024 to 2025 | Nature 2024 · Nature 2025 | periodic | next releases |
| Compute footprint studies | 2021 to 2022 | Adv Sci 2021 · MBE 2022 | one-off | new studies |
| Vertex company report | 2026 | page read 2026-11-03 | quarterly | next quarterly report |
| Illumina trade events | 2025 | Feb to Nov 2025 | per event | current status |
| System | Coverage | Thinnest dimension |
|---|---|---|
| Therapies | PARTIAL | treatment counts and prices |
| Data resources | GOOD | ancestry balance on a common basis |
| Governance | PARTIAL | national rule texts |
| Finance | THIN | payer and price data |
| Energy | THIN | sequencing and cold-chain energy |
| Supply | THIN | consumables and reagents |
| Skills | THIN | workforce beyond counselling |
| Agriculture and environment | THIN | edited crop and animal data |
| Field | Source that would fill it | Blocker |
|---|---|---|
| Energy and cooling use of sequencing laboratories and cell-therapy cold chains | laboratories, manufacturers, peer-reviewed footprint studies | not retrieved; only compute footprints were read2122 |
| NHGRI cost per genome series values | NHGRI sequencing cost data table13 | the page shows graphs and a linked Excel table; the values were not read |
| Independent cost per genome at scale | service providers, national laboratories, published cost studies | only vendor list prices were read, and the Ultima page shows both USD 60 and USD 801540 |
| Patients treated with editing therapies, by country | company reports, treatment centre registries, regulators | the first quarter 2026 report gave no counts6; full-year figures come from a search summary35 |
| Prices paid for editing therapies | payers, health technology assessment bodies, company reports | not retrieved |
| Number of people with a sequenced genome worldwide | national programmes, vendors, published tallies | no consolidated series found |
| Ancestry balance of genome datasets on a common basis | cohort papers and diversity monitors | two cohorts and two commentaries read16171819 |
| Sequencer fleet and consumable supply by country | trade statistics, vendor filings | not retrieved; only trade events were read31 |
| Text of Regulation (EU) 2026/1388 from the Official Journal | Official Journal of the European Union36 | not opened; dates and structure come from search summaries |
| FDA draft guidance on the plausible mechanism pathway | FDA guidance page37 | not opened; the November 2025 report was read5 |
| Date and terms on which the FDA lifted the 2025 clinical holds | company and FDA notices39 | search summaries only; sources differ on dates |
| National rules on genetic data, somatic editing and heritable editing | statutes and regulators | not retrieved; the Oviedo text was not opened41 |
| Genomics workforce beyond genetic counsellors | national statistics, surveys | not retrieved; only counsellor figures were read33 |
| Capability rungs beyond approvals and planning | agencies, clinics, laboratories | not reviewed |
A.5Evidence cards, two anchor sources
Published in the New England Journal of Medicine in 2024 by Frangoul and colleagues. Phase 3 single-group study. Role: binds HLT-001. Coverage: patients 12 to 35 years of age.
EVD-XT05-001
Exagamglogene autotemcel for severe sickle cell disease2
Published in Science in 2022 by the Telomere-to-Telomere Consortium. One-off assembly. Role: binds DAT-006. Coverage: one human cell line genome.
EVD-XT05-002
The complete sequence of a human genome11
| Dimension | EVD-XT05-001 | EVD-XT05-002 |
|---|---|---|
| Completeness | one disease; 30 evaluable patients | one genome; all chromosomes except Y gapless |
| Timeliness | interim analysis at median 19.3 months | single release in 2022 |
| Revision | follow-up reports expected | pangenome release builds on it |
| Method transparency | methods and end points published | assembly methods published |
| External validation | peer review | peer review |
Evidence cards to follow in 2027
A.6Publication acceptance record
Editorial self-check at evidence close. Every applicable item carries a disposition; the remaining items are review, approval and deposit.
| Group | Area | Items | Pass | N/A | Pending |
|---|---|---|---|---|---|
| D1 | Identity and scope | 8 | 8 | 0 | 0 |
| D2 | Source and data | 12 | 9 | 1 | 2 |
| D3 | Analysis and models | 12 | 3 | 8 | 1 |
| D4 | Findings and claims | 9 | 8 | 0 | 1 |
| D5 | Figures, tables, maps | 10 | 6 | 2 | 2 |
| D6 | Editorial and citations | 10 | 8 | 0 | 2 |
| D7 | Review and approval | 13 | 0 | 0 | 13 |
| D8 | Artefact and design | 12 | 7 | 0 | 5 |
| D9 | Registry and release | 9 | 0 | 0 | 9 |
Publication gate
- Conditions met
- 14 of 23 at evidence close
- Blocking problems
- none recorded
- Open conditions
- reviews, approval of the exact digest, deposit, registry pointer
Not applicable at baseline
- Model runs
- first runs in Q1 2027
- Maps
- plates in Q2 2027
- Waivers
- none
A.7Status words
| Status | What it means |
|---|---|
| Observed | Measured directly and published by the source. |
| Reported | Published statistics of an official or institutional source. |
| Declared | Stated by the body concerned; not independently measured. |
| Estimated | A Nexus estimate from cited evidence, with its method in Annex A. |
| Modelled | Produced by a stated model from cited inputs. |
| Inferred | Reasoned from cited evidence; not measured. |
| Forecast | A projection by the cited source. |
| Simulated | A simulation result under stated assumptions. |
| Scenario | A conditional statement under stated assumptions; never a prediction. |
| Expert input | Expert judgement, recorded with its basis. |
| Candidate | Proposed for a later edition; not yet evidence. |
| Evidence-quality levels (EQL 1 to 5) grade the source behind a value; they are not a score of the subject. | |
A.8How the edition is made, released and corrected
Every edition is built from a sealed evidence cut, reviewed under three keys, signed and deposited before any site shows it as published; corrections go to Nexus Standards as change proposals and feed the next cut.
| Step | What happens | Source |
|---|---|---|
| 01 Evidence arrives from the pillars | Foundry seals observations and indicator series, Universe hands over after-action and scenario findings, and contributions are screened at every gateway, including this site’s. | |
| 02 The cut is sealed | On the cut date the evidence is pinned under one identifier, so anyone can rebuild the edition from exactly what it was built on. | |
| 03 The edition is assembled | The edition is drafted from its template and content pack. Agents may draft; they never publish and never decide. | |
| 04 The keys turn | At the publisher of record the truth key comes first: every value is checked against its source or stated method before the meaning and capital keys turn. No edition moves on until every key has been turned by a named steward. | |
| 05 The gate opens | A named approver releases one exact digest of the edition; any change after this point is a new version, never a silent edit. | |
| 06 Signed and deposited | The PDF, the web edition and the data bundle are signed together with a manifest and an RO-Crate description, and deposited on Zenodo with a concept and a version DOI. | |
| 07 Published on its desk’s site | Only then does the edition show as published on its desk’s Reports site, and the Collection lists it as a part. | |
| 08 Corrections go to Standards | Method and correction findings go to Nexus Standards as change proposals; citations, corrections and new contributions feed the next evidence cut. |
A teaching model of the process, not a forecast and not a record of any run; dates and counts on this page come from the programme record. Sources: Reports governance at GCRI Canada (2026); Zenodo, repository of record for Reports deposits (2026).
Lifecycle, one state at a time: Draft, Computed, Evidence bound, Reviewed, Approved for release, Published, Corrected, Superseded. This edition is a draft.
A.9Glossary and abbreviations
| Term | Meaning |
|---|---|
| Baseline Edition | the inaugural annual edition that fixes the reference state for the series |
| WEFH+B | water, energy, food, health and biodiversity, the national nexus core |
| Coupling | a typed dependency through which one system transmits to another |
| Protection gap | the share of losses not covered by insurance |
| Capability ladder | LISTED → EXISTS → ADEQUATE → TESTED → DEMONSTRATED |
| EQL | evidence-quality level, 1–5 |
| Evidence cut | a frozen resolution of exact sources and versions |
| NNC · NLC · NWG | National Nexus Consortium · National Leadership Council · National Working Groups |
| Abbreviation | Expansion |
|---|---|
| bp | base pairs |
| CRISPR | clustered regularly interspaced short palindromic repeats |
| exa-cel | exagamglogene autotemcel |
| FDA | US Food and Drug Administration |
| GWAS | genome-wide association study |
| LNP | lipid nanoparticle |
| NDAA | National Defense Authorization Act |
| NEJM | New England Journal of Medicine |
| OMB | US Office of Management and Budget |
| T2T | Telomere-to-Telomere |
| TDT | transfusion-dependent beta-thalassaemia |
| WHO | World Health Organization |
A.10Technical annex
| Item | Annex | Contents | Status |
|---|---|---|---|
| A.1 | Indicator definitions | the global indicator set, with units and sources | IN THIS EDITION |
| A.2 | Coupling strengths | the twenty-cell matrix and its rationale | IN THIS EDITION |
| A.3 | Scenario specification | SCN-XT05-DLV-01 assumptions and signposts | IN THIS EDITION |
| A.4 | Capability placements | rung evidence for fifteen functions | IN THIS EDITION |
| A.5 | Model diagnostics | first runs and validation | 2027 |
| A.6 | Sensitivity analyses | influence of coupling strengths | 2027 |
| A.7 | Cluster notes | cards for the major sequencing and cell-therapy clusters | 2027 |
| A.8 | Review statements | pass-by-pass review record | AT RELEASE |
A.1 · indicator definition: transfusion independence
- Construct
- a weighted average haemoglobin level of 9 g per decilitre or higher without red-cell transfusion for at least 12 consecutive months
- Unit
- patients meeting the definition among evaluable patients
- Method
- prespecified interim analysis of an open-label single-group study
- Source
- New England Journal of Medicine 20243
- Uncertainty
- 95% confidence interval 77 to 98 for the 91% result
- Known limits
- interim analysis; short follow-up; no comparison arm
Notes
Numbers are the edition’s reference numbers, so a note reads the same in every chapter. The full list, with every source and its licence, is in Annex C. Annex C, references
- 21Grealey, J. et al., The Carbon Footprint of Bioinformatics, Molecular Biology and Evolution 2022 (abstract read through the Europe PMC record; a software upgrade cut one tool footprint by 73%). Oxford University Press, Oxford. Observation year 2022. Accessed 2026-11-03.back
- 22Lannelongue, L., Grealey, J. and Inouye, M., Green Algorithms: Quantifying the Carbon Footprint of Computation, Advanced Science 2021 (abstract read through the Europe PMC record). Wiley, Weinheim. Observation year 2021. Accessed 2026-11-03.back
- 13National Human Genome Research Institute (ed.), The Cost of Sequencing a Human Genome (fact sheet page; method notes read; the cost values sit in graphs and a linked table that were not read; page updated 16 May 2023). NHGRI, Bethesda. Observation year 2023. Accessed 2026-11-03.back
- 15Ultima Genomics (ed.), germline genetics product page (vendor claim of a USD 60 genome at list price over 4 wafers on the UG200 series; the browser title reads USD 80; vendor evidence, weak). Ultima Genomics, Newark. Observation year 2026. Accessed 2026-11-03.back
- 40UNVERIFIED, not opened: Ultima Genomics (ed.), UG 100 Solaris launch announcement of 24 February 2025 (USD 80 genome at list price), taken from search-result summaries; vendor evidence, weak. Ultima Genomics, Newark. Observation year 2025. Accessed 2026-11-03.back
- 6Vertex Pharmaceuticals (ed.), Vertex Reports First Quarter 2026 Financial Results (company press release read through a wire page; Casgevy revenue USD 42.9 million against USD 14.2 million; pediatric submission completed; company statement, weak evidence). Vertex, Boston. Observation year 2026. Accessed 2026-11-03.back
- 35UNVERIFIED, not opened: Vertex Pharmaceuticals (ed.), full-year 2025 results (Casgevy revenue USD 115.8 million in 2025 and USD 10 million in 2024), taken from search-result summaries. Vertex, Boston. Observation year 2025. Accessed 2026-11-03.back
- 16UK Biobank Whole-Genome Sequencing Consortium, Whole-genome sequencing of 490,640 UK Biobank participants, Nature 2025 (abstract read through the Europe PMC record). Springer Nature, London. Observation year 2025. Accessed 2026-11-03.back
- 17All of Us Research Program Genomics Investigators, Genomic data in the All of Us Research Program, Nature 2024 (abstract read through the Europe PMC record; 245,388 genomes; 77% from communities under-represented in research). Springer Nature, London. Observation year 2024. Accessed 2026-11-03.back
- 18Fatumo, S. et al., A roadmap to increase diversity in genomic studies, Nature Medicine 2022 (abstract read through the Europe PMC record). Springer Nature, London. Observation year 2022. Accessed 2026-11-03.back
- 19Sirugo, G., Williams, S.M. and Tishkoff, S.A., The Missing Diversity in Human Genetic Studies, Cell 2019 (abstract read through the Europe PMC record). Cell Press, Cambridge. Observation year 2019. Accessed 2026-11-03.back
- 31MedTech Dive (ed.), China to lift Illumina export ban (trade press, November 2025; listing in February 2025, import ban in March 2025, lift on 10 November 2025, instrument sales in China down 54% in the third quarter; secondary report, weak evidence). Industry Dive, Washington. Observation year 2025. Accessed 2026-11-03.back
- 36UNVERIFIED, not opened: European Parliament and Council, Regulation (EU) 2026/1388 on plants obtained by certain new genomic techniques (adopted 17 June 2026, published 26 June 2026, applies from 17 July 2028), taken from search-result summaries that differ on some dates. Official Journal of the European Union, Luxembourg. Observation year 2026. Accessed 2026-11-03.back
- 37UNVERIFIED, not opened: US Food and Drug Administration (ed.), draft guidance on the plausible mechanism framework for individualised therapies, February 2026, taken from search-result summaries. FDA, Silver Spring. Observation year 2026. Accessed 2026-11-03.back
- 5Clinical Trials Arena (ed.), FDA unveils new pathway to usher bespoke therapies to market (trade press, 13 November 2025; describes the plausible mechanism pathway announced in a journal article by the FDA Commissioner and the CBER Director; secondary report, weak evidence). Clinical Trials Arena, London. Observation year 2025. Accessed 2026-11-03.back
- 39UNVERIFIED, not opened: Intellia Therapeutics and trade press on the lifting of the 2025 clinical holds on the MAGNITUDE trials, taken from search-result summaries that differ on dates. Observation year 2026. Accessed 2026-11-03.back
- 41UNVERIFIED, not opened: Council of Europe (ed.), Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine (Oviedo Convention), 1997, cited from memory; the page returned an access error. Council of Europe, Strasbourg. Observation year 1997. Accessed 2026-11-03.back
- 33US Bureau of Labor Statistics (ed.), Occupational Outlook Handbook: Genetic Counselors (about 4,200 jobs in 2025; median pay USD 100,040 in May 2025; 10% growth projected 2025 to 2035). BLS, Washington. Observation year 2025. Accessed 2026-11-03.back
- 2Frangoul, H. et al., Exagamglogene Autotemcel for Severe Sickle Cell Disease, New England Journal of Medicine 2024 (abstract read through the Europe PMC record; 44 treated, 30 evaluable, 29 free of crises for 12 months or more). Massachusetts Medical Society, Waltham. Observation year 2024. Accessed 2026-11-03.back
- 11Nurk, S. et al., The complete sequence of a human genome, Science 2022 (abstract read through the Europe PMC record; 3.055 billion base pairs; nearly 200 million base pairs of new sequence). American Association for the Advancement of Science, Washington. Observation year 2022. Accessed 2026-11-03.back
- 3Locatelli, F. et al., Exagamglogene Autotemcel for Transfusion-Dependent beta-Thalassemia, New England Journal of Medicine 2024 (abstract read through the Europe PMC record; 52 treated, 35 evaluable, 32 transfusion independent). Massachusetts Medical Society, Waltham. Observation year 2024. Accessed 2026-11-03.back