{ "id": "frontier-20260914-v1", "date": "2026-09-14", "ledgerSourceSha256": "5c9c8c88575b8addbf8183876d5571bada5c1cb8b3649b41650835e1bae2f699", "status": "Conditional computational research, not measured treatment efficacy", "scope": "Public account of all 80 work-package dispositions. Private correspondence, medical records, internal storage paths and third-party attachments are not published.", "ledger": [ { "id": 1, "title": "Define a downstream input contract.", "requirement": "Specify WT and mutant synthesis, survival, surface abundance, activity, units, reference conditions and provenance. Deliverable: a schema distinguishing learned, assumed, simulated and measured quantities.", "accepted": true, "scope": "Per-quantity conditional schema, not empirical ingestion.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 2, "title": "Add absolute-expression capacity.", "requirement": "Extend the ratio-based model to distinguish increasing WT, reducing mutant and increasing both. Deliverable: explicit equations with WT-only and zero-input limits; no invented fitted capacity.", "accepted": true, "scope": "Original conditional mathematical/design deliverable only. No calibrated biological rates, empirical intervention effect, or mechanism identification. See CHECKPOINT_05_ACCEPTANCE.md.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 3, "title": "Add a surface-to-current component.", "requirement": "Keep WT and mutant activity separate and permit distinct gating hypotheses. Deliverable: current scenarios with a documented domain, not inferred current from abundance scores.", "accepted": true, "scope": "Original conditional mathematical/design deliverable only. No calibrated biological rates, empirical intervention effect, or mechanism identification. See CHECKPOINT_05_ACCEPTANCE.md.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 4, "title": "Build downstream adapters.", "requirement": "Connect supplement outputs to forecast-only interfaces. Preserve empty-vector versus WT-partner normalization and never bypass a measurement gate. Deliverable: validated conversions and rejection tests.", "accepted": true, "scope": "Authenticated frozen-source conversion and integrated forecast example; no measured quantities.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 5, "title": "Establish independent numerical tests.", "requirement": "Check units, limiting cases, conservation where stipulated, derivatives and finite changes against a second implementation. Deliverable: saved test results and counterexamples for any failed assertion.", "accepted": true, "scope": "Original conditional mathematical/design deliverable only. No calibrated biological rates, empirical intervention effect, or mechanism identification. See CHECKPOINT_05_ACCEPTANCE.md.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 6, "title": "Separate uncertainty types.", "requirement": "Distinguish numerical error, parameter sensitivity, model disagreement and empirically calibrated uncertainty. Deliverable: an uncertainty/reporting contract that prohibits calling arbitrary grid ranges biological confidence intervals.", "accepted": true, "scope": "Only original computational/design/review deliverable; no empirical validation, clinical claim, backup execution or external release.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 7, "title": "Mutant-selective silencing, route 6.", "requirement": "Model dose-dependent mutant reduction and WT leakage. Deliverable: benefit/reversal boundaries across mechanisms, including partial versus complete reduction.", "accepted": true, "scope": "Only original computational/design/review deliverable; no empirical validation, clinical claim, backup execution or external release.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 8, "title": "Added WT, route 7.", "requirement": "Hold mutant supply fixed and vary WT supply using item 02. Deliverable: absolute response curves with matched WT-background comparisons and explicit capacity dependence.", "accepted": true, "scope": "Original conditional mathematical/design deliverable only. No calibrated biological rates, empirical intervention effect, or mechanism identification. See CHECKPOINT_05_ACCEPTANCE.md.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 9, "title": "Proportional upregulation, route 13.", "requirement": "Increase both alleles while retaining their ratio. Deliverable: supply-dependent surface/current responses; an unchanged ratio must not be mistaken for unchanged output.", "accepted": true, "scope": "Original conditional mathematical/design deliverable only. No calibrated biological rates, empirical intervention effect, or mechanism identification. See CHECKPOINT_05_ACCEPTANCE.md.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 10, "title": "Preferential WT upregulation.", "requirement": "Sweep selectivity and total output separately. Deliverable: selectivity-capacity break-even maps, not a claim that a real intervention achieves those changes.", "accepted": true, "scope": "Only original computational/design/review deliverable; no empirical validation, clinical claim, backup execution or external release.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 11, "title": "MOG1/trafficking modulation, route 10.", "requirement": "State how the intervention changes export, survival or burden before computing its effects. Deliverable: mixed-genotype response scenarios and treated-WT controls.", "accepted": true, "scope": "Original conditional mathematical/design deliverable only. No calibrated biological rates, empirical intervention effect, or mechanism identification. See CHECKPOINT_05_ACCEPTANCE.md.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 12, "title": "Folding correction, route 4.", "requirement": "Test increased survival under competing partner mechanisms. Deliverable: conditions under which stabilization helps or worsens the modeled endpoint; do not assume a stability score establishes a folding lesion.", "accepted": true, "scope": "Original conditional mathematical/design deliverable only. No calibrated biological rates, empirical intervention effect, or mechanism identification. See CHECKPOINT_05_ACCEPTANCE.md.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 13, "title": "Turnover modulation, historical candidate 14.", "requirement": "Separate synthesis, delivery and removal. Deliverable: residence-time sensitivity and prospective contrasts. Do not reinstate the superseded route as validated.", "accepted": true, "scope": "Original conditional mathematical/design deliverable only. No calibrated biological rates, empirical intervention effect, or mechanism identification. See CHECKPOINT_05_ACCEPTANCE.md.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 14, "title": "Coupled-gating perturbation, route 12.", "requirement": "Combine surface scenarios with independently stated functional coupling. Deliverable: contrasts distinguishing surface loss from activity loss, including effects on WT controls.", "accepted": true, "scope": "Original conditional mathematical/design deliverable only. No calibrated biological rates, empirical intervention effect, or mechanism identification. See CHECKPOINT_05_ACCEPTANCE.md.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 15, "title": "Combination interventions.", "requirement": "Only after single-intervention models pass, examine a small justified set such as silencing plus WT addition. Deliverable: interaction maps with explicit assumptions, not an exhaustive combinatorial sweep.", "accepted": true, "scope": "Conditional computation only; independent review accepted. Item39 zero-cap domain qualification corrected and fourth test added/passed after review. No empirical efficacy or calibrated probabilities.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 16, "title": "Across-model intervention comparison.", "requirement": "Identify conclusions shared by the stipulated models and conclusions that reverse. Deliverable: a robustness matrix, not a forced treatment ranking.", "accepted": true, "scope": "Conditional computation only; independent review accepted. Item39 zero-cap domain qualification corrected and fourth test added/passed after review. No empirical efficacy or calibrated probabilities.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 17, "title": "Find explicit reversal witnesses.", "requirement": "For each purported robust benefit, seek admissible counterexamples. Deliverable: reproducible witness parameters or a bounded proof with its exact domain.", "accepted": true, "scope": "Original conditional mathematical/design deliverable only. No calibrated biological rates, empirical intervention effect, or mechanism identification. See CHECKPOINT_05_ACCEPTANCE.md.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 18, "title": "Identify influential missing quantities.", "requirement": "Determine which assumptions control intervention ranking or sign. Deliverable: a prioritized information-needs map; no probability-weighted value-of-information claim without justified probabilities.", "accepted": true, "scope": "Original conditional mathematical/design deliverable only. No calibrated biological rates, empirical intervention effect, or mechanism identification. See CHECKPOINT_05_ACCEPTANCE.md.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 19, "title": "Test intervention-specific identifiability.", "requirement": "Ask whether proposed abundance/current observations distinguish the new intervention models. Deliverable: identifiable combinations and unresolved alternatives beyond the already completed baseline counterexamples.", "accepted": true, "scope": "Original conditional mathematical/design deliverable only. No calibrated biological rates, empirical intervention effect, or mechanism identification. See CHECKPOINT_05_ACCEPTANCE.md.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 20, "title": "Extend the activity-bound application.", "requirement": "Use correctly referenced surface and separately assumed current scenarios to forecast possible bounds. Deliverable: conditional bounds with denominator and background checks, never a measured activity estimate.", "accepted": true, "scope": "Only original computational/design/review deliverable; no empirical validation, clinical claim, backup execution or external release.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 21, "title": "Define stopping rules.", "requirement": "Set when additional parameter sweeps, model variants or simulations cease to change a decision. Deliverable: a stop/continue checklist for each executed branch.", "accepted": true, "scope": "Reviewed design/decision document only; no assay validation, calibrated power or actual lab execution.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 22, "title": "Reconcile the proposed experiments with meeting evidence.", "requirement": "Separate documented agreement, remembered discussion and later computational proposals. Deliverable: an evidence-graded experiment list; do not call all proposals “laboratory's plan.”", "accepted": true, "scope": "Evidence-graded reconciliation of existing correspondence audit and late-call record; not a fresh complete transcript or inbox review.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 23, "title": "Specify observable requirements.", "requirement": "Distinguish total GFP, total WT protein, WT surface, mutant surface and current. Deliverable: a readout-to-inference table, building on existing gates rather than duplicating them.", "accepted": true, "scope": "Reviewed design/decision document only; no assay validation, calibrated power or actual lab execution.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 24, "title": "Resolve exact construct configuration.", "requirement": "Seek sequence-bearing maps, tag/linker placement, isoform and H558 background. Deliverable: a verified construct record or explicit unresolved fields; reference models remain usable as reference models.", "accepted": true, "scope": "Explicit unresolved construct fields; no claim that actual laboratory stocks were authenticated.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 25, "title": "Model DNA-to-synthesis mismatch.", "requirement": "Test expression imbalance independently of nominal plasmid ratio. Deliverable: sensitivity of the predicted ordering to actual synthesis ratios.", "accepted": true, "scope": "Reviewed design/decision document only; no assay validation, calibrated power or actual lab execution.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 26, "title": "Design nuisance controls.", "requirement": "Evaluate how reporter maturation, background and expression burden could mimic the new predictions. Deliverable: an experiment-specific control matrix, not another generic dimming counterexample.", "accepted": true, "scope": "Reviewed design/decision document only; no assay validation, calibrated power or actual lab execution.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 27, "title": "Select discriminating ratios.", "requirement": "Compare candidate conditions by separation of model predictions under stated noise. Deliverable: a compact proposed panel and conditions where discrimination fails.", "accepted": true, "scope": "Candidate comparison under declared noise, not calibrated power or an approved panel.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 28, "title": "Write the prospective decision ledger.", "requirement": "For each candidate observation, state what it supports, refutes or cannot distinguish. Deliverable: dated, versioned falsification criteria before outcome data are available.", "accepted": true, "scope": "Reviewed design/decision document only; no assay validation, calibrated power or actual lab execution.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 29, "title": "Calibrate power and uncertainty.", "requirement": "Obtain preparation-level variance, covariance, backgrounds and allocation information. At home, make sensitivity curves; deliver a real sample-size calculation only when inputs justify it.", "accepted": true, "scope": "Assumed preparation-level power sensitivity only; actual allocation remains pilot-dependent.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 30, "title": "Prepare phenotype-driven follow-up.", "requirement": "Map outcomes to trafficking, turnover, interaction or functional follow-up. Deliverable: a staged decision tree; actual assays remain lab work, not computationally completed measurements.", "accepted": true, "scope": "Reviewed design/decision document only; no assay validation, calibrated power or actual lab execution.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 31, "title": "Base-editor design audit, route 1.", "requirement": "Check reference context, intended edit, editing-window assumptions and bystanders in existing candidates. Deliverable: a versioned candidate comparison with unsupported assumptions flagged.", "accepted": true, "scope": "Versioned existing base-editor reference/window/bystander audit, not efficacy.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 32, "title": "Off-target analysis audit.", "requirement": "Reconcile existing specificity results, reference assemblies, paralogs and tool settings. Deliverable: reproducible computational specificity evidence, not proof of biological off-target absence.", "accepted": true, "scope": "Bounded inherited specificity workflow audited and reproduced; no exhaustive all-build/all-alignment certification. MUC2 correction retained separately.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 33, "title": "Prime-editing design audit, route 3.", "requirement": "Verify existing pegRNA/nicking configurations and sequence provenance. Deliverable: a candidate panel with computational rationale and unresolved empirical efficiency.", "accepted": true, "scope": "All 6480 existing candidates verified against local reference for sequence/product/nick configuration; 88-family panel and exact reproduction. No empirical efficiency or safety.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 34, "title": "RNA-editing design audit, route 2.", "requirement": "Review target accessibility assumptions, intended/bystander edits and transcript specificity. Deliverable: a source-grounded candidate table.", "accepted": true, "scope": "Source-grounded RNA candidate/proxy specificity audit, not biochemical specificity or accessibility validation.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 35, "title": "Silencing-sequence selectivity bridge.", "requirement": "Connect computational discrimination assumptions to the WT-leakage model in item 07. Deliverable: required selectivity ranges; do not equate sequence prediction with measured knockdown.", "accepted": true, "scope": "Only original computational/design/review deliverable; no empirical validation, clinical claim, backup execution or external release.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 36, "title": "Editing-to-functional-rescue bridge.", "requirement": "Distinguish fraction edited, allele output and function. Deliverable: mosaic correction scenarios rather than treating editing percentage as current recovery percentage.", "accepted": true, "scope": "Only original computational/design/review deliverable; no empirical validation, clinical claim, backup execution or external release.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 37, "title": "Native-RNA versus cDNA evidence map.", "requirement": "Identify which observations address splicing, RNA abundance or protein behavior. Deliverable: a denominator-aware evidence table; no multiplying incompatible assay scores.", "accepted": true, "scope": "Completed predecessor distinguishes native RNA, minigene and conditional cDNA contexts and incompatible denominators.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 38, "title": "Recover ParSE replicate mapping.", "requirement": "Look for source-group keys, original replicate files or processed per-barcode replicate tables. Deliverable: verified mapping or a bounded negative search; no bulk reprocessing with invented labels.", "accepted": true, "scope": "Bounded negative search and authenticated current public-blob comparison, as explicitly permitted by original deliverable. Missing PSI inputs remain missing; no inferred replicate labels.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 39, "title": "Productive-transcript flux model, route 5.", "requirement": "Separate production, splice fractions and decay/NMD assumptions. Deliverable: conditional ceilings with explicit cell/context limitations.", "accepted": true, "scope": "Conditional computation only; independent review accepted. Item39 zero-cap domain qualification corrected and fourth test added/passed after review. No empirical efficacy or calibrated probabilities.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 40, "title": "Recover APC normalization provenance.", "requirement": "Identify the transformation, controls and raw-to-processed mapping needed for historical score interpretation. Deliverable: reproducible transformation or a precise unresolved-source statement.", "accepted": true, "scope": "Precise unresolved normalization-source statement, as explicitly permitted by original deliverable. No exact linear-current reconstruction claimed.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 41, "title": "Recover missing source supplements/exports.", "requirement": "Target the specific O'Neill/cohort/calibration materials still unresolved in current audits; verify they are not already present before requesting them. Deliverable: real source files, provenance and endpoint qualifications.", "accepted": false, "scope": "The intended outcome remains unmet. Useful preparation and alternatives are complete.", "dependency": "Authenticated original ONeill supplemental workbook and specified cohort raw exports not recovered.", "reopen": "A genuinely new legitimate source location or author-supplied original becomes available.", "alternative": "Use already qualified source-scale summaries and conditional scenarios; retain provisional transcription labels." }, { "id": 42, "title": "Evaluate protected-data access feasibility.", "requirement": "Determine whether needed cardiac transcript data are accessible through authorized channels. Deliverable: access requirements or a public-data alternative, not bypassed access controls.", "accepted": true, "scope": "Authorized-access feasibility and alternatives, not acquisition of protected reads.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 43, "title": "Audit mechanistic claim strength.", "requirement": "Separate predicted destabilization, abundance, assembly, surface effects and functional dominance. Deliverable: a claim-to-evidence matrix that prevents one endpoint becoming another.", "accepted": true, "scope": "Scoped endpoint/claim matrix, not universal historical claim repair.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 44, "title": "Seek genuinely independent endpoint labels.", "requirement": "Identify new NTD abundance/partner-function labels not used for gating or model selection. Deliverable: versioned coverage and overlap audit; no new calibration on recycled examples.", "accepted": true, "scope": "Versioned bounded independent-label coverage audit with negative search result; no new calibration.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 45, "title": "Recover the historical full nomination score table.", "requirement": "Check specific new source locations for Paper 9's missing artifact. Deliverable: authenticated historical output or a documented distinction from any fresh scoring run.", "accepted": true, "scope": "Historical-output recovery distinction; missing full nomination table remains missing.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 46, "title": "Extend predictor benchmarking only with a new testable question.", "requirement": "Require independent labels, versioned models and held-out evaluation. Deliverable: a benchmark that could reject the proposed transfer; retain the existing failed partner transfer.", "accepted": false, "scope": "The intended outcome remains unmet. Useful preparation and alternatives are complete.", "dependency": "No new independent-label held-out benchmark executed.", "reopen": "Independent endpoint-compatible labels and a new falsifiable transfer question are identified.", "alternative": "Preserve the completed failed partner transfer and bounded negative coverage audit; no recycled-label calibration." }, { "id": 47, "title": "Qualify NTD interaction geometry.", "requirement": "Search source evidence for relevant resolved contacts or testable structural hypotheses. Deliverable: geometry provenance and limitations; no passing off a predicted pose as established assembly.", "accepted": true, "scope": "Bounded geometry qualification, including resolved homolog intrachain contacts and related-class control; no target intermolecular interface established.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 48, "title": "Background/isoform interaction analysis.", "requirement": "Keep Q1077, H558 and beta1 context separate where evidence permits. Deliverable: context-specific assumptions or comparisons, not an inferred actual backbone or effects from identical scenario labels.", "accepted": true, "scope": "Conditional background/configuration register, not actual backbone or empirical interaction.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 49, "title": "Reconcile current simulation inventory.", "requirement": "Identify completed, failed, excluded, queued and recoverable runs from authoritative outputs. Deliverable: a run ledger with hashes and explicit live-status verification when performed.", "accepted": true, "scope": "Bounded hashed run inventory; historical records are not current live telemetry.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 50, "title": "Qualify physical systems.", "requirement": "Check sequence, construct identity, matched WT/mutant preparation, force-field choices and boundary conditions. Deliverable: per-system acceptance/rejection record before production.", "accepted": true, "scope": "Per-system hold/rejection disposition; zero newly accepted production systems.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 51, "title": "Audit existing trajectories for interpretable comparisons.", "requirement": "Assess equilibration, stability, independent replicas and effective sampling. Deliverable: usable analysis windows and uncertainty limits; simulation length alone is not convergence.", "accepted": true, "scope": "Conservative descriptive metric-window disposition; no equilibrium or comparative inference window accepted.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 52, "title": "Design decision-driven additional MD.", "requirement": "Specify the observable, control, expected decision impact and stopping criterion first. Deliverable: a bounded run plan; actual execution requires readiness and authorized compute scope.", "accepted": true, "scope": "Observable-first conditional MD plan; no production execution claimed.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 53, "title": "Resolve ligand/PMF validity issues.", "requirement": "Recheck chemical identity, sampling correlation and the claims attached to historical calculations. Deliverable: valid analyses or explicit exclusions, not a new binding claim from sparse sampling.", "accepted": true, "scope": "Explicit retained ligand/PMF exclusions; no corrected affinity result.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 54, "title": "Establish measured resource planning.", "requirement": "Benchmark accepted systems on the actual workstation configuration when available. Deliverable: measured throughput, storage growth and restart plan; do not scale laptop timing into GPU ETAs.", "accepted": false, "scope": "The intended outcome remains unmet. Useful preparation and alternatives are complete.", "dependency": "No accepted-system actual-host throughput/storage-growth/restart benchmark executed.", "reopen": "Intended physical system passes admission and fresh verified RAID budget supports a bounded benchmark.", "alternative": "Use explicit byte lower bounds and restart/admission checklist; no fabricated GPU rate or silent system substitution." }, { "id": 55, "title": "Bridge cellular scenarios to tissue inputs.", "requirement": "State the gating/conductance assumptions between cell output and tissue models. Deliverable: scenario mappings with no claim of patient calibration.", "accepted": true, "scope": "Conditional cellular-to-tissue input mapping only, no solver integration or patient calibration.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 56, "title": "Improve anatomical/model calibration.", "requirement": "Identify appropriate human geometry, regional properties and independent reference data. Deliverable: documented calibration targets or explicit generic-model status.", "accepted": true, "scope": "Explicit generic-model status and field-level calibration dependencies; no anatomical reconstruction.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 57, "title": "Test new delivery-heterogeneity questions.", "requirement": "Preserve spatial placement and beat sequence; extend only beyond already completed masks/grid tests. Deliverable: a distinct, verified endpoint comparison, not recycled capture thresholds.", "accepted": true, "scope": "Six-case coarse-grid missed-stimulus endpoint comparison verified; no continuum convergence, patient calibration or efficacy claim. Optional fine-grid extension not activated.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 58, "title": "BacNav and S10s comparisons, routes 11A/11B.", "requirement": "Separate surrogate-channel behavior from accessory-protein effects and beta1 context. Deliverable: qualified scenario comparisons; no transfer of source-study efficacy to WT/R104Q by assumption.", "accepted": true, "scope": "Qualified conditional component/scenario comparison, not new tissue-efficacy simulation.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 59, "title": "Consolidate allele-resolved proteomics design.", "requirement": "Review the existing Lys-C/trypsin rationale, peptide uniqueness and isoform numbering. Deliverable: a source-linked candidate/readout brief, not proof of detection or quantitation.", "accepted": true, "scope": "Only original computational/design/review deliverable; no empirical validation, clinical claim, backup execution or external release.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 60, "title": "Define proteomics validation needs.", "requirement": "Identify standards, recovery, detection and quantitation requirements. Deliverable: a minimal validation checklist; actual sensitivity and allele counts remain empirical.", "accepted": true, "scope": "Only original computational/design/review deliverable; no empirical validation, clinical claim, backup execution or external release.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 61, "title": "Maintain the variant evidence resource.", "requirement": "Add only genuinely new source evidence with release/version tracking. Deliverable: a delta from the completed census, not a redundant census rebuild.", "accepted": true, "scope": "Bounded eight-field R104Q resource delta, not gene-wide census or all assertion-content comparison.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 62, "title": "Reconcile public classification claims.", "requirement": "Distinguish functional evidence, mechanism prediction and clinical classification. Deliverable: an evidence/provenance audit; no automatic clinical reclassification from this supplement.", "accepted": true, "scope": "Scoped clinical/function/mechanism provenance audit; no clinical reclassification.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 63, "title": "Draft the computational supplement manuscript.", "requirement": "Explain the executed models, benchmark limitations, predictions and falsifiers. Deliverable: a self-contained scientific draft, not competition prose or publication submission.", "accepted": true, "scope": "Self-contained working scientific draft with methods; not publication or final goal report.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 64, "title": "Build an intervention-results supplement after execution.", "requirement": "Include adapters, assumptions, robustness maps and tests from A-C. Deliverable: reproducible new results, not promises labeled as findings.", "accepted": true, "scope": "Executed intervention-results supplement content; final package manifest remains separate.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 65, "title": "Create audience-specific figures.", "requirement": "Show model disagreement, intervention sensitivity and observation limits from saved arrays. Deliverable: reproducible figures with prediction labels and exact provenance.", "accepted": true, "scope": "Three reproducible scientific figures with source rows and captions; final PDF remains separate.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 66, "title": "Audit remaining overbroad historical claims.", "requirement": "Prioritize mechanism closure, MD interpretation and universal route-blocker statements. Deliverable: a scoped correction proposal; preserve published/historical originals and completed corrections.", "accepted": true, "scope": "Scoped historical overclaim correction proposal, not universal cleanup.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 67, "title": "Assemble a concise laboratory discussion packet.", "requirement": "Combine the prospective prediction, a discriminating comparison and only essential unresolved configuration questions. Deliverable: an unsent packet; recheck correspondence before any actual outreach.", "accepted": true, "scope": "Concise unsent computational discussion packet; no finalized experimental agreement implied.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 68, "title": "Prepare publication/version decisions.", "requirement": "Identify the intended record, version and artifacts needing release. Deliverable: owner-review checklist; local readiness is not authorization to upload, submit or email.", "accepted": true, "scope": "Owner-review release/version checklist; destination choice and upload remain unapproved.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 69, "title": "Adjudicate reference candidates.", "requirement": "Classify the 315 candidates from the latest check as broken, historical, ambiguous or intentional. Deliverable: evidence-backed repair list; do not substitute arbitrary basename matches.", "accepted": true, "scope": "All 340 captured baseline reference candidates adjudicated; repair list and 19 installed navigation changes, not all links repaired.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 70, "title": "Resolve three historical simulation-claim defects.", "requirement": "Compare flagged prose with primary arrays and correction ledgers. Deliverable: scoped correction with preserved history, not a blanket numeric rewrite.", "accepted": true, "scope": "Only original computational/design/review deliverable; no empirical validation, clinical claim, backup execution or external release.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 71, "title": "Refresh stale navigation and dependency summaries.", "requirement": "Link current work without changing frozen supplement artifacts. Deliverable: a reviewed update plan that distinguishes completed, conditional and source-gated work.", "accepted": true, "scope": "Reviewed scoped active navigation update; older handoff preserved, no global pointer clearance.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 72, "title": "Address the additional privacy warning safely.", "requirement": "An existing handoff flags potentially private content outside the restricted home. Deliverable: owner-directed containment review without opening or indexing that content in research scans.", "accepted": true, "scope": "Owner-directed privacy review preparation without opening restricted content; no containment execution certificate.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 73, "title": "Define backup verification.", "requirement": "Distinguish saved, committed and independently backed-up artifacts. Deliverable: checksum/restore verification plan with private versus shareable exports kept separate; do not assume the deferred backup happened.", "accepted": true, "scope": "Only original computational/design/review deliverable; no empirical validation, clinical claim, backup execution or external release.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 74, "title": "Add reproducibility status for new outputs.", "requirement": "Record input hashes, versions, test outcomes and limitations. Deliverable: an auditable manifest for future intervention results, leaving the completed supplement freeze intact.", "accepted": true, "scope": "Independently verified 456-file research inventory, source-specific input provenance, 17-script results, tissue campaign manifest, four figures and eight-page visually reviewed PDF. Local reproducibility package only; not biological validation, release approval or independent backup.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 75, "title": "Verify workstation access and storage before new compute.", "requirement": "Check actual remote availability, free space and intended SATA RAID work locations when execution is requested. Deliverable: current readiness snapshot, not inherited infrastructure claims.", "accepted": true, "scope": "Timestamped actual-host readiness observation, not present resource reservation.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 76, "title": "Define bounded compute scheduling.", "requirement": "Separate CPU analysis, GPU MD and model inference; cap concurrency to measured resources. Deliverable: checkpointed queue with observable progress and no unnecessary LLM polling.", "accepted": true, "scope": "Checkpointed bounded research queue, not an operating scheduler.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 77, "title": "Audit recoverable storage growth.", "requirement": "Identify generated caches, abandoned temporary work and retained simulation outputs before proposing cleanup. Deliverable: exact-target retention/cleanup plan; no automatic deletion or source-data deduplication.", "accepted": true, "scope": "Exact-target bounded retention plan: retain both reviewed scientific workdirs; zero proven reclaimable bytes and no cleanup performed.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 78, "title": "Test the prospective surface/function predictions.", "requirement": "Use qualified observations and controls to adjudicate the models. At-home deliverable: locked analysis plan; empirical outcome cannot be supplied by simulation.", "accepted": false, "scope": "The intended outcome remains unmet. Useful preparation and alternatives are complete.", "dependency": "Analysis plan is not assay-locked or registered; no experimental test performed.", "reopen": "Actual construct/readout, primary contrast/margin, preparation allocation and QC/uncertainty choices are resolved before relevant outcome access.", "alternative": "Retain timestamped four-file preparation snapshot, conditional predictions and parameterized decision rules without inventing assay choices." }, { "id": 79, "title": "Test intervention response in the relevant mixed genotype.", "requirement": "Assess whether the intervention changes surface and function as forecast, with treated-WT controls. At-home deliverable: decision thresholds and analysis templates, not established rescue.", "accepted": true, "scope": "Parameterized decision thresholds and templates; numerical assay-specific margins remain to be chosen.", "dependency": "", "reopen": "", "alternative": "" }, { "id": 80, "title": "Develop the translation evidence ladder.", "requirement": "Identify expression, delivery, tissue effects, durability and safety evidence required beyond cellular results. At-home deliverable: a staged research roadmap with specialist review needs; no self-treatment or patient efficacy inference.", "accepted": true, "scope": "Only original computational/design/review deliverable; no empirical validation, clinical claim, backup execution or external release.", "dependency": "", "reopen": "", "alternative": "" } ], "tests": [ { "script": "test_foundation.py", "sha256": "9e41d795793f4a993268c411c896e5b28eb35428b5d2ed3ebc9c2545bdfbef1b", "passed": true, "seconds": 0.0536098328884691 }, { "script": "test_forecast_v2.py", "sha256": "cdd619352c9b463579261cd53194ab067444c7b53a9674e545fdfcc2c3833a2e", "passed": true, "seconds": 0.037848749896511436 }, { "script": "test_intervention_actions_v2.py", "sha256": "688386af59e9f49bc73d7a4ab116ffc716b7c6cc2237dca8a459f12e127f632a", "passed": true, "seconds": 0.035815499955788255 }, { "script": "test_monotonicity_v2.py", "sha256": "89e95c9d91af3073052d1ecc579fc655752e9acc2ba46b6c6a8186e6b8985997", "passed": true, "seconds": 0.05042683403007686 }, { "script": "test_small_bridges.py", "sha256": "f0fa070fa5e54df044c198b23ccdf108e88ffc930f7d0fccaef68cef32f9b032", "passed": true, "seconds": 0.03897279198281467 }, { "script": "test_identifiability_recovery.py", "sha256": "def427abd15d571b54fc0989d378ea20d385165da55efd6e8c694a04140fdc61", "passed": true, "seconds": 0.0403410829603672 }, { "script": "test_rna_flux_ceiling.py", "sha256": "9920c987f2766ef584d8d7fb366245ed3c00350e6cb7884ac82507fbcf038883", "passed": true, "seconds": 0.03777529206126928 }, { "script": "test_record_contract.py", "sha256": "d65c0f1a0bba25ad5bb2350ae5e6d238c60c7c0c9950e27dfa35052c46112158", "passed": true, "seconds": 0.03959937486797571 }, { "script": "test_activity_bound.py", "sha256": "f2dff3b1d61cda3c36a543068c47d6809dace0b571a48862c4156d6f2e9056e5", "passed": true, "seconds": 0.04005820909515023 }, { "script": "test_partner_reference_adapter.py", "sha256": "6cfead02229a7ccbde0733eb04a1aa77fddd67f8ac820ea88302d516923a5c81", "passed": true, "seconds": 0.034662083024159074 }, { "script": "test_quantity_provenance_bridge.py", "sha256": "6ae78c56715d9872fdd0b2d49ad3699f693908f228f1e80d4104fef1f4c613ee", "passed": true, "seconds": 0.3101964578963816 }, { "script": "test_tissue_forecast_adapter.py", "sha256": "3af0b8b964f034cbcc20566bab6c4254e2bec61ff8310383a82d775ec7a9ea7f", "passed": true, "seconds": 0.03655145806260407 }, { "script": "verify_v2_analytic_review.py", "sha256": "3a4c280d70813ab805b6fbcfdad61df702c1dda5a284dd46a134cf93529b0d2f", "passed": true, "seconds": 0.036629458190873265 }, { "script": "verify_all_frozen_conversions.py", "sha256": "1b6fb1671a8e051f22998f3ffc91dfedfefefc4a12969cc624d05498289c0696", "passed": true, "seconds": 0.2398188340011984 }, { "script": "verify_frozen_preservation.py", "sha256": "ec7880618a607a19e36dcb72f940b2ac53b8d22191189d0d63c134e6e4e72c30", "passed": true, "seconds": 0.10550691722892225 }, { "script": "verify_pe_lead_reproduction.py", "sha256": "fc4dbee682dab65289f2dd820230c10d838f69cc87968323f478385d558526c8", "passed": true, "seconds": 0.06757095782086253 }, { "script": "verify_pe_panel_reproduction.py", "sha256": "11ab1da96c277467ceca7d549b85f405658c4e3f491a9ca7d6e3b7812d3a05e9", "passed": true, "seconds": 0.20833008317276835 } ] }