Antibody triage and assay-conditioned rescue

Choose the synthesis set. Design the next round.

BioFold reads paired VH and VL libraries with assay conditions and buyer constraints. It returns a hard-gated Pareto shortlist before synthesis, then routes observed failures to zero to three legal single-substitution proposals, each with modeled target and guard tradeoffs.

Before synthesisHard constraints, Pareto tiers, lineage diversity, uncertainty
After assayFailure route, exhaustive legal search, target and guard deltas
Every decisionApplicability, responsible residues, evidence status, provenance
Every CDR editBinding requirement, new liabilities, falsifier

Open the sample report See rescue proposals Inspect the API contract

Example library · BF-EX-024 Sample report

Synthesis decisionPre-assay

Candidates: 5 paired VH/VL
Budget: 2 sequences
Decision: 2 SYNTHESIZE
Coverage: 2 lineages
Other states: 2 DEFER
Applicability: 1 ABSTAIN

Next-round decisionObserved failure

Parent: BF-018
Failure: High HIC retention
Legal edits: 168
Proposals: 3 non-dominated
State: PROPOSE
Guard: Binding assay required

Example library Static sample values Exportable trace

One workflow, two decision moments

One record covers both decision moments.

BioFold allocates a fixed synthesis budget before assay. An observed failure then starts a rescue decision that either returns legal edits for testing or names why no proposal is justified.

01 · Before synthesis

Build the admissible shortlist.

BioFold applies declared hard constraints, evaluates supported physical and assay fields, partitions admissible candidates into Pareto tiers, then fills the budget with visible lineage and diversity rules.

Input: Paired VH/VL library, assay conditions, budget, protected positions, missing-value policy
Decision: SYNTHESIZE, DEFER, or ABSTAIN
Trace: Hard gates, Pareto tier, lineage, uncertainty, applicability, tie-break, provenance

02 · After assay

Route the failure before proposing an edit.

The measured phenotype selects the target axis. BioFold enumerates every allowed single substitution, rejects hard guard failures, and returns zero to three non-dominated proposals with distinct target and guard tradeoffs.

Input: Observed assay failure, parent sequences, assay protocol, protected positions, optional structure
Decision: PROPOSE, NEEDS_STRUCTURE, NEEDS_ASSAY, or ABSTAIN
Trace: Routed axis, legal count, exact deltas, new liabilities, binding requirement, falsifier

Interactive sample report

Every state is visible, including abstention.

Switch between the library decision and the next-round rescue record. The desktop tables and mobile cards carry the same fields.

BF-EX-024 is a synthetic example for contract inspection. Its values demonstrate output shape and do not claim measured product performance.

Library: BF-EX-024 · 5 paired candidates
Assay condition: HIC · pH 6.0 · 150 mM · 25 °C
Buyer constraints: Budget 2 · one selected candidate per lineage
Hard gates: Protected positions, disulfides, forbidden motifs
Selection method: Constrained Pareto tiers with declared tie-breaks
Provenance: Sample buyer model IDs, chain mappings, component and policy versions, input and output hashes

Synthesis budget2

Selected2

Lineages represented2

Abstentions1

Candidate states for the BF-EX-024 example library
Candidate	Lineage	Coverage	Principal axis	Assay direction	Hard constraints	Pareto tier	Uncertainty	Decision
`BF-021`	LIN-A	VH/VL, CDR, and structure mapped	Hydrophobic surface drive	Lower HIC retention	PASS	1	LOW	SYNTHESIZE
`BF-044`	LIN-B	VH/VL, CDR, and structure mapped	Hydrophobic surface drive	Lower HIC retention	PASS	1	LOW	SYNTHESIZE
`BF-018`	LIN-A	VH/VL, CDR, and structure mapped	Hydrophobic surface drive	Lower HIC retention	PASS	2	MODERATE	DEFER
`BF-031`	LIN-C	VH/VL, CDR, and structure mapped	Chemical sites	Not modeled after hard-gate failure	FAIL · forbidden NVT	Not assigned	LOW	DEFER
`BF-077`	LIN-D	CDR mapping unresolved	Not evaluated	Not evaluated	Not evaluated	Not assigned	Not estimated	ABSTAIN

BF-021

Lineage: LIN-A
Coverage: VH/VL, CDR, and structure mapped
Principal axis: Hydrophobic surface drive
Assay direction: Lower HIC retention
Hard constraints: PASS
Pareto tier: 1
Uncertainty: LOW
Decision: SYNTHESIZE

BF-044

Lineage: LIN-B
Coverage: VH/VL, CDR, and structure mapped
Principal axis: Hydrophobic surface drive
Assay direction: Lower HIC retention
Hard constraints: PASS
Pareto tier: 1
Uncertainty: LOW
Decision: SYNTHESIZE

BF-018

Lineage: LIN-A
Coverage: VH/VL, CDR, and structure mapped
Principal axis: Hydrophobic surface drive
Assay direction: Lower HIC retention
Hard constraints: PASS
Pareto tier: 2
Uncertainty: MODERATE
Decision: DEFER

BF-031

Lineage: LIN-C
Coverage: VH/VL, CDR, and structure mapped
Principal axis: Chemical sites
Assay direction: Not modeled after hard-gate failure
Hard constraints: FAIL · forbidden NVT
Pareto tier: Not assigned
Uncertainty: LOW
Decision: DEFER

BF-077

Lineage: LIN-D
Coverage: CDR mapping unresolved
Principal axis: Not evaluated
Assay direction: Not evaluated
Hard constraints: Not evaluated
Pareto tier: Not assigned
Uncertainty: Not estimated
Decision: ABSTAIN

Evidence classes: hydrophobic surface drive, charge, and licensed charge texture are DERIVED; chemical-site rules are CONVENTIONAL; HIC observations and stability guards are EMPIRICAL or FITTED as labeled in the downloaded record.

BF-018 is deferred by Pareto tier and the declared lineage cap. BF-031 fails a buyer hard constraint. BF-077 abstains because canonical CDR mapping is unresolved, so unsupported fields never become favorable zeros.

Observed failure: BF-018 · HIC 14.6 min · pass at or below 11.0 min
Routed axis: hydrophobic_surface_drive
Search: Every allowed single substitution · sample buyer structure mapped
Legal mutation count: 168 after hard guards
Proposal set: 3 non-dominated alternatives
Binding requirement: Required for every CDR edit

Primary rescue case

`BF-RES-401` · PROPOSE

Each row reports the target-axis delta, every modeled guard delta, new liabilities, and the experiment required before adoption.

Three non-dominated proposals for the BF-RES-401 sample rescue case
Role	Edit	Target delta	Charge delta	Chemical sites	Sequence stability guard, higher is better	Structure stability guard	New liabilities	Binding	State
PRIMARY	`H:W99Y`	24.9 → 20.7 kJ/mol (Δ −4.2)	+1.10 → +1.10 e (Δ 0.00)	0 → 0 sites	0.00 → +0.03 dimensionless	0.00 → 0.00 dimensionless · PASS	None	Required	PROPOSE
ALTERNATIVE	`H:W99S`	24.9 → 18.1 kJ/mol (Δ −6.8)	+1.10 → +1.10 e (Δ 0.00)	0 → 0 sites	0.00 → −0.11 dimensionless	0.00 → 0.00 dimensionless · PASS	None	Required	PROPOSE
ALTERNATIVE	`L:F94Y`	24.9 → 21.8 kJ/mol (Δ −3.1)	+1.10 → +1.10 e (Δ 0.00)	0 → 0 sites	0.00 → +0.08 dimensionless	0.00 → 0.00 dimensionless · PASS	None	Required	PROPOSE

H:W99Y

Role: PRIMARY
Target: 24.9 → 20.7 kJ/mol (Δ −4.2)
Charge: +1.10 → +1.10 e (Δ 0.00)
Chemical sites: 0 → 0 sites
Sequence stability guard: 0.00 → +0.03 dimensionless
Structure stability guard: 0.00 → 0.00 dimensionless · PASS
New liabilities: None
Binding: Required
State: PROPOSE

H:W99S

Role: ALTERNATIVE
Target: 24.9 → 18.1 kJ/mol (Δ −6.8)
Charge: +1.10 → +1.10 e (Δ 0.00)
Chemical sites: 0 → 0 sites
Sequence stability guard: 0.00 → −0.11 dimensionless
Structure stability guard: 0.00 → 0.00 dimensionless · PASS
New liabilities: None
Binding: Required
State: PROPOSE

L:F94Y

Role: ALTERNATIVE
Target: 24.9 → 21.8 kJ/mol (Δ −3.1)
Charge: +1.10 → +1.10 e (Δ 0.00)
Chemical sites: 0 → 0 sites
Sequence stability guard: 0.00 → +0.08 dimensionless
Structure stability guard: 0.00 → 0.00 dimensionless · PASS
New liabilities: None
Binding: Required
State: PROPOSE

Evidence classes: observed HIC is EMPIRICAL; target and charge deltas are DERIVED; chemical-site deltas are CONVENTIONAL; stability guards are EMPIRICAL. Structure-derived fields name the sample buyer model in the downloaded record.

Separate experimental controls

Controls come from the same legal single-substitution table. They test the routed direction and never count among the three recommendations.

Neutral and adverse experimental controls for BF-RES-401
Role	Selection rule	Paired assay	Recommendation count
NEUTRAL CONTROL	Legal edit with near-zero target movement and matched guard burden	HIC	Excluded
ADVERSE CONTROL	Legal edit with opposite target movement and matched guard burden	HIC	Excluded

NEUTRAL CONTROL

Selection rule: Legal edit with near-zero target movement and matched guard burden
Paired assay: HIC
Recommendation count: Excluded

ADVERSE CONTROL

Selection rule: Legal edit with opposite target movement and matched guard burden
Paired assay: HIC
Recommendation count: Excluded

Sample rescue states

Examples of every rescue decision state
Case	Observed failure	Routed axis	Legal edits	Proposals	State
`BF-RES-401`	High HIC retention	Hydrophobic surface drive	168	3	PROPOSE
`BF-RES-226`	Named Met oxidation	Chemical site context	0	0	NEEDS_STRUCTURE
`BF-RES-118`	Assay named, value absent	Not routed	0	0	NEEDS_ASSAY
`BF-RES-903`	Affinity loss	Outside rescue scope	0	0	ABSTAIN

BF-RES-401

Observed failure: High HIC retention
Routed axis: Hydrophobic surface drive
Legal edits: 168
Proposals: 3
State: PROPOSE

BF-RES-226

Observed failure: Named Met oxidation
Routed axis: Chemical site context
Legal edits: 0
Proposals: 0
State: NEEDS_STRUCTURE

BF-RES-118

Observed failure: Assay named, value absent
Routed axis: Not routed
Legal edits: 0
Proposals: 0
State: NEEDS_ASSAY

BF-RES-903

Observed failure: Affinity loss
Routed axis: Outside rescue scope
Legal edits: 0
Proposals: 0
State: ABSTAIN

Falsifier: the rescue policy fails if its negative target-delta edits do not outperform matched neutral and adverse controls on paired HIC, or if a proposed edit breaches a buyer-defined binding, stability, charge, chemistry, or protected-position guard.

Assay failure router

Observed phenotype selects the rescue question.

BioFold routes ten declared failure classes. Each route names the target axis, the required guards, and the state returned when the required evidence is absent.

BioFold assay failure router with ten observed failure classes
Observed failure	Routed objective	Required guards or inputs	Decision route
High HIC or SMAC retention	Reduce exposed or CDR-localized nonpolar drive	Charge, chemistry, stability, protected residues	PROPOSE after legal search
High PSR, BVP, CIC, or related polyspecificity	Reduce implicated positive charge state or texture	Hydrophobicity, declared pH, protected residues, binding assay	PROPOSE when the assay mapping applies
High AC-SINS or self-association with a charge signature	Move charge state or asymmetry in the supported direction	Assay-specific mapping and binding assay	PROPOSE when the charge route is applicable
Oxidation at a named Met or Trp	Remove or shield the named chemical site	Structure context, binding, stability	NEEDS_STRUCTURE before shielding claims
Deamidation or isomerization at a named motif	Remove the motif or reduce local reactivity	Paired assay evidence or validated geometry context	NEEDS_ASSAY when context evidence is absent
Explicit free cysteine or unwanted sequon	Remove the rule liability	Required disulfides and function constraints	PROPOSE after deterministic motif guards
Low thermal stability	Filter with sequence stability, then use structure-gated ranking	Admissible structure for packing and backbone deltas	ABSTAIN when the sequence guard is unresolved and no admissible structure is supplied
Low expression without a mapped liability	No physical route assigned	Additional assay or mechanism evidence	ABSTAIN
Affinity or potency loss	Outside the rescue model	Buyer affinity model or experiment	ABSTAIN
Conformational or folding failure without structure	No sequence-only route assigned	Structure or a separately validated mechanism	NEEDS_STRUCTURE

01 · High HIC or SMAC retention

Objective: Reduce exposed or CDR-localized nonpolar drive
Guards: Charge, chemistry, stability, protected residues
Route: PROPOSE after legal search

02 · High PSR, BVP, CIC, or related polyspecificity

Objective: Reduce implicated positive charge state or texture
Guards: Hydrophobicity, declared pH, protected residues, binding assay
Route: PROPOSE when the assay mapping applies

03 · High AC-SINS or self-association with a charge signature

Objective: Move charge state or asymmetry in the supported direction
Guards: Assay-specific mapping and binding assay
Route: PROPOSE when the charge route is applicable

04 · Oxidation at a named Met or Trp

Objective: Remove or shield the named chemical site
Guards: Structure context, binding, stability
Route: NEEDS_STRUCTURE before shielding claims

05 · Deamidation or isomerization at a named motif

Objective: Remove the motif or reduce local reactivity
Guards: Paired assay evidence or validated geometry context
Route: NEEDS_ASSAY when context evidence is absent

06 · Explicit free cysteine or unwanted sequon

Objective: Remove the rule liability
Guards: Required disulfides and function constraints
Route: PROPOSE after deterministic motif guards

07 · Low thermal stability

Objective: Filter with sequence stability, then use structure-gated ranking
Guards: Admissible structure for packing and backbone deltas
Route: ABSTAIN when the sequence guard is unresolved and no admissible structure is supplied

08 · Low expression without a mapped liability

Objective: No physical route assigned
Guards: Additional assay or mechanism evidence
Route: ABSTAIN

09 · Affinity or potency loss

Objective: Outside the rescue model
Guards: Buyer affinity model or experiment
Route: ABSTAIN

10 · Conformational or folding failure without structure

Objective: No sequence-only route assigned
Guards: Structure or a separately validated mechanism
Route: NEEDS_STRUCTURE

Physical vector and guards

The vector records modeled target and guard tradeoffs alongside the decision.

Each component keeps its definition, units, assumptions, structural requirements, applicability, uncertainty, and responsible residues. Assay mappings and buyer thresholds remain separate.

`hydrophobic_surface_drive`

State-dependent solvent excess free-energy output with volume, surface, curvature, connectivity, and local chemistry contributions. Rescue reports the exact mutant delta.

`charge_state`

Total charge at the declared pH, plus localized positive and negative charge texture when the assay contract licenses those fields.

`chemical_sites`

Named oxidation, deamidation, isomerization, cysteine, and sequon sites with motif, context gate, residue location, and evidence class.

`stability_guard_sequence`

A sequence-level substitution guard used for rejection, warnings, or unresolved states. It does not stand in for affinity, expression, or foldability.

`stability_guard_structure`

Packing and backbone checks run only when an admissible structure has recorded provenance and chain mapping.

`coverage_and_applicability`

Component coverage, assumptions, out-of-distribution state, missing fields, uncertainty drivers, and the exact reason for any abstention.

Proposal guard register

Hard rejection

Protected residues, canonical cysteines, required disulfides, forbidden amino acids, forbidden motifs, invalid mappings.

Target and guard deltas

The complete mutant vector is recomputed. Each proposal reports target movement, charge, chemistry, sequence stability, structure stability when available, and new liabilities.

Binding requirement

Every CDR edit carries binding_guard_required: true. The report names the required binding or potency experiment.

No hidden scalar

Pareto dominance preserves competing objectives. Declared buyer priorities break ties without changing physical or assay fields.

Deterministic ordering

Input order does not change the result. A dominated candidate ranks below its dominator unless a declared buyer constraint explains the outcome.

API contract

Two endpoints. One inspectable decision record.

The examples below are complete and valid JSON. Requests carry paired sequences, assay conditions, and buyer constraints. Responses use the same states and fields shown in the sample report.

Library decision: POST /v1/antibody/triage
Next-round decision: POST /v1/antibody/rescue

POST /v1/antibody/triageantibody.triage.v1

Triage requestComplete example

{
  "contract_version": "antibody.triage.v1",
  "sample": true,
  "library": {
    "library_id": "BF-EX-024",
    "candidates": [
      {
        "candidate_id": "BF-021",
        "lineage_id": "LIN-A",
        "vh_sequence": "EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARWGGDGFYAMDYWGQGTLVTVSS",
        "vl_sequence": "DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCLQHNSYPWTFGQGTKVEIK",
        "known_parent_id": null,
        "mutation_history": [],
        "structure": {"source_type": "BUYER_MODEL", "source_id": "sample-buyer-model-BF-021", "evidence_class": "CONVENTIONAL", "chain_mapping": {"VH": "A", "VL": "B"}}
      },
      {
        "candidate_id": "BF-044",
        "lineage_id": "LIN-B",
        "vh_sequence": "EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARSGGDGFYAMDYWGQGTLVTVSS",
        "vl_sequence": "DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCLQHNSYPWTFGQGTKVEIK",
        "known_parent_id": null,
        "mutation_history": [],
        "structure": {"source_type": "BUYER_MODEL", "source_id": "sample-buyer-model-BF-044", "evidence_class": "CONVENTIONAL", "chain_mapping": {"VH": "A", "VL": "B"}}
      },
      {
        "candidate_id": "BF-018",
        "lineage_id": "LIN-A",
        "vh_sequence": "EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARWGGWGFWAMDYWGQGTLVTVSS",
        "vl_sequence": "DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCLQHNSFPWTFGQGTKVEIK",
        "known_parent_id": null,
        "mutation_history": [],
        "structure": {"source_type": "BUYER_MODEL", "source_id": "sample-buyer-model-BF-018", "evidence_class": "CONVENTIONAL", "chain_mapping": {"VH": "A", "VL": "B"}}
      },
      {
        "candidate_id": "BF-031",
        "lineage_id": "LIN-C",
        "vh_sequence": "EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARNVTGDFYAMDYWGQGTLVTVSS",
        "vl_sequence": "DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCLQHNSYPWTFGQGTKVEIK",
        "known_parent_id": null,
        "mutation_history": [],
        "structure": {"source_type": "BUYER_MODEL", "source_id": "sample-buyer-model-BF-031", "evidence_class": "CONVENTIONAL", "chain_mapping": {"VH": "A", "VL": "B"}}
      },
      {
        "candidate_id": "BF-077",
        "lineage_id": "LIN-D",
        "vh_sequence": "QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGRIDPSDSETRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCARGGYYGMDVWGQGTTVTVSS",
        "vl_sequence": "EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPTFGQGTKVEIK",
        "known_parent_id": null,
        "mutation_history": [],
        "structure": null
      }
    ]
  },
  "assay_context": {
    "target_assays": [
      {
        "assay": "HIC",
        "protocol_id": "sample-hic-protocol.v1",
        "pass_criterion": {"operator": "<=", "value": 11.0, "unit": "min", "evidence_class": "CONVENTIONAL"},
        "desirability": "lower_is_better"
      }
    ],
    "buffer": {"pH": 6.0, "ionic_strength_mM": 150, "formulation": "phosphate buffered saline"},
    "concentration_mg_mL": 1.0,
    "temperature_C": 25,
    "missing_value_policy": "ABSTAIN"
  },
  "buyer_constraints": {
    "synthesis_budget": 2,
    "lineage_cap": 1,
    "protected_residues": [
      {"chain": "H", "positions": [33, 50, 52], "reason": "affinity critical"}
    ],
    "protected_motifs": [],
    "allowed_mutation_regions": ["H3", "L3"],
    "maximum_substitutions_per_proposal": 1,
    "cdr_mutation_policy": "ALLOW_WITH_BINDING_GUARD",
    "preserve_canonical_cysteines": true,
    "preserve_disulfides": true,
    "forbidden_amino_acids": [],
    "forbidden_motifs": ["NXS", "NXT"],
    "declared_tie_breakers": ["lower_HIC_estimate", "lineage_diversity", "candidate_id_ascending"]
  }
}

Triage responseAll shortlist states

{
  "contract_version": "antibody.triage.v1",
  "request_id": "req_triage_example_024",
  "sample": true,
  "library_id": "BF-EX-024",
  "policy": {
    "selection_method": "CONSTRAINED_PARETO",
    "synthesis_budget": 2,
    "lineage_cap": 1,
    "declared_tie_breakers": ["lower_HIC_estimate", "lineage_diversity", "candidate_id_ascending"]
  },
  "summary": {
    "candidate_count": 5,
    "synthesize_count": 2,
    "defer_count": 2,
    "abstain_count": 1,
    "selected_lineage_count": 2
  },
  "component_contracts": {
    "hydrophobic_surface_drive": {"version": "hydrophobic-surface-drive.v1", "assumptions": ["buyer_structure_chain_mapping_accepted", "declared_thermodynamic_state"], "required_structure": true},
    "charge_state": {"version": "charge-state.v1", "assumptions": ["declared_pH", "isolated_group_protonation"]},
    "positive_charge_texture": {"version": "charge-texture.v1", "assumptions": ["buyer_structure_chain_mapping_accepted", "observation_model_licensed"]},
    "negative_charge_texture": {"version": "charge-texture.v1", "assumptions": ["buyer_structure_chain_mapping_accepted", "observation_model_licensed"]},
    "chemical_sites": {"version": "chemical-sites.v1", "assumptions": ["canonical_motif_rules", "full_sequence_rescan"]},
    "stability_guard_sequence": {"version": "stability-sequence-guard.v1", "assumptions": ["single_substitution_guard"], "direction_of_desirability": "higher_is_better"},
    "stability_guard_structure": {"version": "stability-structure-guard.v1", "assumptions": ["buyer_structure_chain_mapping_accepted"], "direction_of_desirability": "higher_is_better"}
  },
  "candidate_results": [
    {
      "candidate_id": "BF-021",
      "lineage_id": "LIN-A",
      "hard_constraints": {"state": "PASS", "reasons": []},
      "pareto_tier": 1,
      "diversity": {"selected_lineage_representative": true},
      "applicability": {"state": "APPLICABLE", "coverage": "VH_VL_CDR_AND_STRUCTURE_MAPPED"},
      "uncertainty": {"state": "LOW", "drivers": []},
      "physical_vector": {
        "hydrophobic_surface_drive": {"value": 18.2, "unit": "kJ/mol", "evidence_class": "DERIVED", "structure_source": "sample-buyer-model-BF-021", "responsible_residues": ["H:W99"]},
        "charge_state": {"value": -0.4, "unit": "e", "pH": 6.0, "evidence_class": "DERIVED"},
        "positive_charge_texture": {"value": 0.21, "unit": "dimensionless", "evidence_class": "DERIVED"},
        "negative_charge_texture": {"value": 0.34, "unit": "dimensionless", "evidence_class": "DERIVED"},
        "chemical_sites": {"evidence_class": "CONVENTIONAL", "sites": []},
        "stability_guard_sequence": {"state": "PASS", "evidence_class": "EMPIRICAL"},
        "stability_guard_structure": {"state": "PASS", "evidence_class": "EMPIRICAL", "structure_source": "sample-buyer-model-BF-021"}
      },
      "assay_observations": {
        "HIC": {
          "estimate": {"value": 8.7, "unit": "min", "evidence_class": "FITTED"},
          "direction": "lower_is_better",
          "mapping_version": "hic.observation.v1",
          "applicable_conditions": "pH_6.0_ionic_strength_150_mM",
          "applicable_cohort": "paired_VH_VL_with_accepted_chain_mapping",
          "uncertainty": "LOW",
          "out_of_distribution": false
        }
      },
      "decision": {"shortlist_position": 1, "state": "SYNTHESIZE", "reason": "pareto_tier_1_and_lineage_rule"},
      "decision_trace": ["hard_constraints_pass", "applicability_pass", "pareto_tier_1", "lineage_cap_pass", "budget_fill"]
    },
    {
      "candidate_id": "BF-044",
      "lineage_id": "LIN-B",
      "hard_constraints": {"state": "PASS", "reasons": []},
      "pareto_tier": 1,
      "diversity": {"selected_lineage_representative": true},
      "applicability": {"state": "APPLICABLE", "coverage": "VH_VL_CDR_AND_STRUCTURE_MAPPED"},
      "uncertainty": {"state": "LOW", "drivers": []},
      "physical_vector": {
        "hydrophobic_surface_drive": {"value": 17.6, "unit": "kJ/mol", "evidence_class": "DERIVED", "structure_source": "sample-buyer-model-BF-044", "responsible_residues": ["H:Y105"]},
        "charge_state": {"value": 0.2, "unit": "e", "pH": 6.0, "evidence_class": "DERIVED"},
        "positive_charge_texture": {"value": 0.28, "unit": "dimensionless", "evidence_class": "DERIVED"},
        "negative_charge_texture": {"value": 0.27, "unit": "dimensionless", "evidence_class": "DERIVED"},
        "chemical_sites": {"evidence_class": "CONVENTIONAL", "sites": []},
        "stability_guard_sequence": {"state": "PASS", "evidence_class": "EMPIRICAL"},
        "stability_guard_structure": {"state": "PASS", "evidence_class": "EMPIRICAL", "structure_source": "sample-buyer-model-BF-044"}
      },
      "assay_observations": {
        "HIC": {
          "estimate": {"value": 9.3, "unit": "min", "evidence_class": "FITTED"},
          "direction": "lower_is_better",
          "mapping_version": "hic.observation.v1",
          "applicable_conditions": "pH_6.0_ionic_strength_150_mM",
          "applicable_cohort": "paired_VH_VL_with_accepted_chain_mapping",
          "uncertainty": "LOW",
          "out_of_distribution": false
        }
      },
      "decision": {"shortlist_position": 2, "state": "SYNTHESIZE", "reason": "pareto_tier_1_and_lineage_rule"},
      "decision_trace": ["hard_constraints_pass", "applicability_pass", "pareto_tier_1", "lineage_cap_pass", "budget_fill"]
    },
    {
      "candidate_id": "BF-018",
      "lineage_id": "LIN-A",
      "hard_constraints": {"state": "PASS", "reasons": []},
      "pareto_tier": 2,
      "diversity": {"selected_lineage_representative": false, "lineage_cap_reached": true},
      "applicability": {"state": "APPLICABLE", "coverage": "VH_VL_CDR_AND_STRUCTURE_MAPPED"},
      "uncertainty": {"state": "MODERATE", "drivers": ["HIC_estimate_near_applicability_edge"]},
      "physical_vector": {
        "hydrophobic_surface_drive": {"value": 24.9, "unit": "kJ/mol", "evidence_class": "DERIVED", "structure_source": "sample-buyer-model-BF-018", "responsible_residues": ["H:W99", "H:W102", "L:F94"]},
        "charge_state": {"value": 1.1, "unit": "e", "pH": 6.0, "evidence_class": "DERIVED"},
        "positive_charge_texture": {"value": 0.46, "unit": "dimensionless", "evidence_class": "DERIVED"},
        "negative_charge_texture": {"value": 0.18, "unit": "dimensionless", "evidence_class": "DERIVED"},
        "chemical_sites": {"evidence_class": "CONVENTIONAL", "sites": []},
        "stability_guard_sequence": {"state": "PASS", "evidence_class": "EMPIRICAL"},
        "stability_guard_structure": {"state": "PASS", "evidence_class": "EMPIRICAL", "structure_source": "sample-buyer-model-BF-018"}
      },
      "assay_observations": {
        "HIC": {
          "estimate": {"value": 13.8, "unit": "min", "evidence_class": "FITTED"},
          "direction": "lower_is_better",
          "mapping_version": "hic.observation.v1",
          "applicable_conditions": "pH_6.0_ionic_strength_150_mM",
          "applicable_cohort": "paired_VH_VL_with_accepted_chain_mapping",
          "uncertainty": "MODERATE",
          "out_of_distribution": false
        }
      },
      "decision": {"shortlist_position": null, "state": "DEFER", "reason": "pareto_tier_2_and_lineage_cap"},
      "decision_trace": ["hard_constraints_pass", "applicability_pass", "pareto_tier_2", "lineage_cap_reached", "defer"]
    },
    {
      "candidate_id": "BF-031",
      "lineage_id": "LIN-C",
      "hard_constraints": {"state": "FAIL", "reasons": ["forbidden_motif_NVT_at_H99_H101"]},
      "pareto_tier": null,
      "diversity": {"selected_lineage_representative": false},
      "applicability": {"state": "APPLICABLE", "coverage": "VH_VL_CDR_AND_STRUCTURE_MAPPED"},
      "uncertainty": {"state": "LOW", "drivers": []},
      "physical_vector": {
        "hydrophobic_surface_drive": {"value": 19.4, "unit": "kJ/mol", "evidence_class": "DERIVED", "structure_source": "sample-buyer-model-BF-031", "responsible_residues": ["H:Y105"]},
        "charge_state": {"value": 0.3, "unit": "e", "pH": 6.0, "evidence_class": "DERIVED"},
        "positive_charge_texture": {"value": 0.29, "unit": "dimensionless", "evidence_class": "DERIVED"},
        "negative_charge_texture": {"value": 0.24, "unit": "dimensionless", "evidence_class": "DERIVED"},
        "chemical_sites": {"evidence_class": "CONVENTIONAL", "sites": [{"motif": "NVT", "chain": "H", "start_position": 99, "context": "unwanted_sequon"}]},
        "stability_guard_sequence": {"state": "PASS", "evidence_class": "EMPIRICAL"},
        "stability_guard_structure": {"state": "PASS", "evidence_class": "EMPIRICAL", "structure_source": "sample-buyer-model-BF-031"}
      },
      "assay_observations": {"HIC": {"estimate": {"value": null, "unit": "min", "evidence_class": "UNSUPPORTED"}, "state": "NOT_EVALUATED", "reason": "buyer_hard_constraint_failed", "direction": "lower_is_better", "mapping_version": "hic.observation.v1", "applicable_cohort": "paired_VH_VL_with_accepted_chain_mapping", "applicable_conditions": "pH_6.0_ionic_strength_150_mM", "uncertainty": "NOT_ESTIMATED", "out_of_distribution": false}},
      "decision": {"shortlist_position": null, "state": "DEFER", "reason": "buyer_hard_constraint_failed"},
      "decision_trace": ["hard_constraint_failed", "pareto_not_assigned", "defer"]
    },
    {
      "candidate_id": "BF-077",
      "lineage_id": "LIN-D",
      "hard_constraints": {"state": "NOT_EVALUATED", "reasons": ["canonical_CDR_mapping_unresolved"]},
      "pareto_tier": null,
      "diversity": {"selected_lineage_representative": false},
      "applicability": {"state": "OUT_OF_SCOPE", "coverage": "VH_VL_PRESENT_CDR_MAPPING_UNRESOLVED"},
      "uncertainty": {"state": "NOT_ESTIMATED", "drivers": ["mapping_unresolved"]},
      "physical_vector": {
        "hydrophobic_surface_drive": {"value": null, "unit": "kJ/mol", "evidence_class": "UNSUPPORTED", "status": "ABSTAIN", "reason": "canonical_CDR_mapping_unresolved"},
        "charge_state": {"value": null, "unit": "e", "pH": 6.0, "evidence_class": "UNSUPPORTED", "status": "ABSTAIN", "reason": "required_mapping_unresolved"},
        "positive_charge_texture": {"value": null, "unit": "dimensionless", "evidence_class": "UNSUPPORTED", "status": "ABSTAIN", "reason": "required_mapping_unresolved"},
        "negative_charge_texture": {"value": null, "unit": "dimensionless", "evidence_class": "UNSUPPORTED", "status": "ABSTAIN", "reason": "required_mapping_unresolved"},
        "chemical_sites": {"sites": null, "evidence_class": "UNSUPPORTED", "status": "ABSTAIN", "reason": "required_mapping_unresolved"},
        "stability_guard_sequence": {"state": "ABSTAIN", "evidence_class": "UNSUPPORTED", "reason": "required_mapping_unresolved"},
        "stability_guard_structure": {"state": "ABSTAIN", "evidence_class": "UNSUPPORTED", "reason": "structure_and_chain_mapping_unavailable"}
      },
      "assay_observations": {"HIC": {"estimate": {"value": null, "unit": "min", "evidence_class": "UNSUPPORTED"}, "state": "ABSTAIN", "reason": "required_physical_axis_unavailable", "direction": "lower_is_better", "mapping_version": "hic.observation.v1", "applicable_cohort": "paired_VH_VL_with_accepted_chain_mapping", "applicable_conditions": "pH_6.0_ionic_strength_150_mM", "uncertainty": "NOT_ESTIMATED", "out_of_distribution": true}},
      "decision": {"shortlist_position": null, "state": "ABSTAIN", "reason": "applicability_failed"},
      "decision_trace": ["mapping_unresolved", "applicability_failed", "unsupported_fields_not_zeroed", "abstain"]
    }
  ],
  "provenance": {
    "engine_version": "biofold-antibody-1.0.0",
    "physical_object_version": "physical-vector.v1",
    "observation_versions": ["hic.observation.v1"],
    "policy_version": "triage.policy.v1",
    "hash_scope": {"input": "sha256_of_UTF8_JSON.stringify_request", "output": "sha256_of_UTF8_JSON.stringify_response_omitting_provenance.output_hash_and_provenance.served_at"},
    "input_hash": "sha256:f11331e0c1d624befc9e7c88b95849cffcfd28bc5db7f81a5a87b791e19247c1",
    "output_hash": "sha256:f5be9ea1f4fe790b1538bb253477b9f2682c5db09bafe021fb76284f5f22b21f",
    "served_at": "2026-07-10T12:00:00Z"
  }
}

POST /v1/antibody/rescueantibody.rescue.v1

Rescue requestFour routed cases

{
  "contract_version": "antibody.rescue.v1",
  "sample": true,
  "parents": [
    {
      "candidate_id": "BF-018",
      "lineage_id": "LIN-A",
      "vh_sequence": "EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARWGGWGFWAMDYWGQGTLVTVSS",
      "vl_sequence": "DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCLQHNSFPWTFGQGTKVEIK",
      "structure": {"source_type": "BUYER_MODEL", "source_id": "sample-buyer-model-BF-018", "evidence_class": "CONVENTIONAL", "chain_mapping": {"VH": "A", "VL": "B"}}
    },
    {
      "candidate_id": "BF-226",
      "lineage_id": "LIN-E",
      "vh_sequence": "EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSMISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGGYGMDVWGQGTLVTVSS",
      "vl_sequence": "DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCLQHNSYPWTFGQGTKVEIK",
      "structure": null
    },
    {
      "candidate_id": "BF-118",
      "lineage_id": "LIN-F",
      "vh_sequence": "QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYWMHWVRQAPGQGLEWMGRIDPSDSETRYSPSFQGQVTISADKSISTAYLQWSSLKASDTAMYYCARGGYYGMDVWGQGTTVTVSS",
      "vl_sequence": "EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTISSLEPEDFAVYYCQQRSNWPPTFGQGTKVEIK",
      "structure": null
    },
    {
      "candidate_id": "BF-903",
      "lineage_id": "LIN-G",
      "vh_sequence": "EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARGGYYGMDVWGQGTLVTVSS",
      "vl_sequence": "DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCLQHNSYPWTFGQGTKVEIK",
      "structure": null
    }
  ],
  "assay_protocols": [
    {"protocol_id": "sample-hic-protocol.v1", "assay": "HIC", "version": "1", "conditions_ref": "assay_context"},
    {"protocol_id": "sample-oxidation-protocol.v1", "assay": "MET_OXIDATION", "version": "1", "conditions_ref": "assay_context"},
    {"protocol_id": "sample-spr-protocol.v1", "assay": "SPR_KD", "version": "1", "conditions_ref": "assay_context"},
    {"protocol_id": "sample-binding-guard.v1", "assay": "SPR_KD", "version": "1", "conditions_ref": "assay_context"},
    {"protocol_id": "sample-expression-guard.v1", "assay": "transient_expression_titer", "version": "1", "conditions_ref": "assay_context"},
    {"protocol_id": "sample-stability-guard.v1", "assay": "DSF_Tm", "version": "1", "conditions_ref": "assay_context"}
  ],
  "cases": [
    {
      "case_id": "BF-RES-401",
      "candidate_id": "BF-018",
      "observed_failure": {"assay": "HIC", "protocol_id": "sample-hic-protocol.v1", "value": 14.6, "unit": "min", "evidence_class": "EMPIRICAL", "failure_criterion": {"operator": ">", "value": 11.0, "unit": "min", "evidence_class": "CONVENTIONAL"}, "confidence": "CONFIRMED"},
      "guard_assays": {
        "binding": {"assay": "SPR_KD", "protocol_id": "sample-binding-guard.v1", "value": 3.2, "unit": "nM", "pass_criterion": {"operator": "<=", "value": 5.0, "unit": "nM", "evidence_class": "CONVENTIONAL"}, "state": "PASS", "evidence_class": "EMPIRICAL"},
        "expression": {"assay": "transient_expression_titer", "protocol_id": "sample-expression-guard.v1", "value": 125, "unit": "mg/L", "pass_criterion": {"operator": ">=", "value": 100, "unit": "mg/L", "evidence_class": "CONVENTIONAL"}, "state": "PASS", "evidence_class": "EMPIRICAL"},
        "stability": {"assay": "DSF_Tm", "protocol_id": "sample-stability-guard.v1", "value": 68.1, "unit": "degC", "pass_criterion": {"operator": ">=", "value": 65.0, "unit": "degC", "evidence_class": "CONVENTIONAL"}, "state": "PASS", "evidence_class": "EMPIRICAL"}
      }
    },
    {
      "case_id": "BF-RES-226",
      "candidate_id": "BF-226",
      "observed_failure": {"assay": "MET_OXIDATION", "protocol_id": "sample-oxidation-protocol.v1", "value": 18.0, "unit": "percent", "evidence_class": "EMPIRICAL", "failure_criterion": {"operator": ">", "value": 10.0, "unit": "percent", "evidence_class": "CONVENTIONAL"}, "named_site": "H:M34", "confidence": "CONFIRMED"},
      "guard_assays": {
        "binding": {"assay": "SPR_KD", "protocol_id": "sample-binding-guard.v1", "value": 4.1, "unit": "nM", "pass_criterion": {"operator": "<=", "value": 5.0, "unit": "nM", "evidence_class": "CONVENTIONAL"}, "state": "PASS", "evidence_class": "EMPIRICAL"},
        "expression": {"assay": "transient_expression_titer", "protocol_id": "sample-expression-guard.v1", "value": 132, "unit": "mg/L", "pass_criterion": {"operator": ">=", "value": 100, "unit": "mg/L", "evidence_class": "CONVENTIONAL"}, "state": "PASS", "evidence_class": "EMPIRICAL"},
        "stability": {"assay": "DSF_Tm", "protocol_id": "sample-stability-guard.v1", "value": 66.9, "unit": "degC", "pass_criterion": {"operator": ">=", "value": 65.0, "unit": "degC", "evidence_class": "CONVENTIONAL"}, "state": "PASS", "evidence_class": "EMPIRICAL"}
      }
    },
    {
      "case_id": "BF-RES-118",
      "candidate_id": "BF-118",
      "observed_failure": {"assay": "HIC", "protocol_id": "sample-hic-protocol.v1", "value": null, "unit": "min", "evidence_class": "UNSUPPORTED", "failure_criterion": {"operator": ">", "value": 11.0, "unit": "min", "evidence_class": "CONVENTIONAL"}, "confidence": "MISSING_VALUE"},
      "guard_assays": {
        "binding": {"assay": "SPR_KD", "protocol_id": "sample-binding-guard.v1", "value": 3.7, "unit": "nM", "pass_criterion": {"operator": "<=", "value": 5.0, "unit": "nM", "evidence_class": "CONVENTIONAL"}, "state": "PASS", "evidence_class": "EMPIRICAL"},
        "expression": {"assay": "transient_expression_titer", "protocol_id": "sample-expression-guard.v1", "value": 118, "unit": "mg/L", "pass_criterion": {"operator": ">=", "value": 100, "unit": "mg/L", "evidence_class": "CONVENTIONAL"}, "state": "PASS", "evidence_class": "EMPIRICAL"},
        "stability": {"assay": "DSF_Tm", "protocol_id": "sample-stability-guard.v1", "value": 67.4, "unit": "degC", "pass_criterion": {"operator": ">=", "value": 65.0, "unit": "degC", "evidence_class": "CONVENTIONAL"}, "state": "PASS", "evidence_class": "EMPIRICAL"}
      }
    },
    {
      "case_id": "BF-RES-903",
      "candidate_id": "BF-903",
      "observed_failure": {"assay": "SPR_KD", "protocol_id": "sample-spr-protocol.v1", "value": 45.0, "unit": "nM", "evidence_class": "EMPIRICAL", "failure_criterion": {"operator": ">", "value": 10.0, "unit": "nM", "evidence_class": "CONVENTIONAL"}, "confidence": "CONFIRMED"},
      "guard_assays": {
        "binding": {"assay": "SPR_KD", "protocol_id": "sample-binding-guard.v1", "value": 45.0, "unit": "nM", "pass_criterion": {"operator": "<=", "value": 5.0, "unit": "nM", "evidence_class": "CONVENTIONAL"}, "state": "FAIL", "evidence_class": "EMPIRICAL"},
        "expression": {"assay": "transient_expression_titer", "protocol_id": "sample-expression-guard.v1", "value": 121, "unit": "mg/L", "pass_criterion": {"operator": ">=", "value": 100, "unit": "mg/L", "evidence_class": "CONVENTIONAL"}, "state": "PASS", "evidence_class": "EMPIRICAL"},
        "stability": {"assay": "DSF_Tm", "protocol_id": "sample-stability-guard.v1", "value": 66.2, "unit": "degC", "pass_criterion": {"operator": ">=", "value": 65.0, "unit": "degC", "evidence_class": "CONVENTIONAL"}, "state": "PASS", "evidence_class": "EMPIRICAL"}
      }
    }
  ],
  "assay_context": {
    "buffer": {"pH": 6.0, "ionic_strength_mM": 150, "formulation": "phosphate buffered saline"},
    "concentration_mg_mL": 1.0,
    "temperature_C": 25
  },
  "engineering_constraints": {
    "protected_residues": [
      {"chain": "H", "positions": [33, 50, 52], "reason": "affinity critical"}
    ],
    "protected_motifs": [],
    "allowed_mutation_regions": ["H3", "L3"],
    "allowed_mutation_positions": {"H": [99, 100, 101, 102, 103, 104, 105], "L": [94, 95]},
    "maximum_substitutions_per_proposal": 1,
    "cdr_mutation_policy": "ALLOW_WITH_BINDING_GUARD",
    "binding_or_potency_measurement_commitment": {"accepted": true, "assay": "buyer_binding_or_potency_assay"},
    "preserve_canonical_cysteines": true,
    "preserve_disulfides": true,
    "forbidden_amino_acids": [],
    "forbidden_motifs": ["NXS", "NXT"]
  }
}

Rescue responseZero to three proposals and every state

{
  "contract_version": "antibody.rescue.v1",
  "request_id": "req_rescue_example_024",
  "sample": true,
  "case_results": [
    {
      "case_id": "BF-RES-401",
      "candidate_id": "BF-018",
      "observed_failure": {"assay": "HIC", "protocol_id": "sample-hic-protocol.v1", "value": 14.6, "unit": "min", "evidence_class": "EMPIRICAL", "threshold": 11.0, "threshold_evidence_class": "CONVENTIONAL"},
      "routed_axis": "hydrophobic_surface_drive",
      "applicability": {"state": "APPLICABLE", "reason": "observed_HIC_failure_matches_route"},
      "uncertainty": {"state": "MODERATE", "drivers": ["assay_mapping_uncertainty"]},
      "legal_search": {
        "enumeration": "ALL_CANONICAL_SINGLE_SUBSTITUTIONS",
        "sequence_lengths": {"VH": 120, "VL": 107, "total": 227},
        "canonical_alternatives_per_position": 19,
        "enumerated_count": 4313,
        "complete_legal_substitution_table": {
          "representation": "LOSSLESS_CARTESIAN_MINUS_EXPLICIT_REJECTIONS",
          "positions": [
            {"chain": "H", "position": 99, "parent": "W"},
            {"chain": "H", "position": 100, "parent": "G"},
            {"chain": "H", "position": 101, "parent": "G"},
            {"chain": "H", "position": 102, "parent": "W"},
            {"chain": "H", "position": 103, "parent": "G"},
            {"chain": "H", "position": 104, "parent": "F"},
            {"chain": "H", "position": 105, "parent": "W"},
            {"chain": "L", "position": 94, "parent": "F"},
            {"chain": "L", "position": 95, "parent": "P"}
          ],
          "canonical_residues": ["A", "C", "D", "E", "F", "G", "H", "I", "K", "L", "M", "N", "P", "Q", "R", "S", "T", "V", "W", "Y"],
          "exclude_parent_residue": true,
          "ordering": ["chain", "position", "mutant_residue"],
          "candidate_row_count": 171,
          "excluded_rows": [
            {"row": "L:F94S", "reason": "forbidden_sequon"},
            {"row": "L:F94T", "reason": "forbidden_sequon"},
            {"row": "L:P95N", "reason": "forbidden_sequon"}
          ],
          "row_count": 168
        },
        "hard_rejection_summary": {"outside_allowed_positions": 4142, "protected_positions": 0, "canonical_cysteines": 0, "required_disulfides": 0, "forbidden_residues_or_motifs": 3},
        "legal_mutation_count": 168,
        "non_dominated_count": 3,
        "proposal_membership": [
          {"proposal_id": "BF-RES-401-P1", "legal_row": "H:W99Y"},
          {"proposal_id": "BF-RES-401-P2", "legal_row": "H:W99S"},
          {"proposal_id": "BF-RES-401-P3", "legal_row": "L:F94Y"}
        ]
      },
      "state": "PROPOSE",
      "proposals": [
        {
          "proposal_id": "BF-RES-401-P1",
          "recommendation_role": "PRIMARY",
          "decision": {"state": "PROPOSE", "reason": "non_dominated_primary_tradeoff"},
          "edit": {"chain": "H", "position": 99, "from": "W", "to": "Y", "region": "H3"},
          "responsible_residues": ["H:W99"],
          "parent_vector": {
            "hydrophobic_surface_drive": {"value": 24.9, "unit": "kJ/mol", "evidence_class": "DERIVED", "structure_source": "sample-buyer-model-BF-018"},
            "charge_state": {"value": 1.1, "unit": "e", "pH": 6.0, "evidence_class": "DERIVED"},
            "chemical_sites": {"site_ids": [], "evidence_class": "CONVENTIONAL"},
            "stability_guard_sequence": {"value": 0.0, "unit": "dimensionless", "evidence_class": "EMPIRICAL"},
            "stability_guard_structure": {"value": 0.0, "unit": "dimensionless", "state": "PASS", "evidence_class": "EMPIRICAL", "structure_source": "sample-buyer-model-BF-018"}
          },
          "mutant_vector": {
            "hydrophobic_surface_drive": {"value": 20.7, "unit": "kJ/mol", "evidence_class": "DERIVED", "structure_source": "sample-buyer-model-BF-018"},
            "charge_state": {"value": 1.1, "unit": "e", "pH": 6.0, "evidence_class": "DERIVED"},
            "chemical_sites": {"site_ids": [], "evidence_class": "CONVENTIONAL"},
            "stability_guard_sequence": {"value": 0.03, "unit": "dimensionless", "evidence_class": "EMPIRICAL"},
            "stability_guard_structure": {"value": 0.0, "unit": "dimensionless", "state": "PASS", "evidence_class": "EMPIRICAL", "structure_source": "sample-buyer-model-BF-018"}
          },
          "delta_vector": {
            "hydrophobic_surface_drive": {"value": -4.2, "unit": "kJ/mol", "direction": "DESIRED", "evidence_class": "DERIVED"},
            "charge_state": {"value": 0.0, "unit": "e", "pH": 6.0, "evidence_class": "DERIVED"},
            "chemical_sites": {"added": [], "removed": [], "evidence_class": "CONVENTIONAL"},
            "stability_guard_sequence": {"value": 0.03, "unit": "dimensionless", "evidence_class": "EMPIRICAL", "direction_of_desirability": "higher_is_better", "tradeoff": "DESIRED"},
            "stability_guard_structure": {"value": 0.0, "unit": "dimensionless", "state": "PASS", "evidence_class": "EMPIRICAL"}
          },
          "component_coverage": {"positive_charge_texture": "NOT_LICENSED_FOR_HIC_RESCUE", "negative_charge_texture": "NOT_LICENSED_FOR_HIC_RESCUE"},
          "hard_guards": {"protected_positions": "PASS", "disulfides": "PASS", "forbidden_motifs": "PASS"},
          "new_liabilities": [],
          "binding_guard_required": true,
          "required_binding_assay": "buyer_binding_or_potency_assay",
          "applicability": {"state": "APPLICABLE", "out_of_domain": false},
          "uncertainty": {"state": "MODERATE", "drivers": ["assay_mapping_uncertainty"]},
          "observation_model": {"assay": "HIC", "mapping_version": "hic.observation.v1", "conditions": "pH_6.0_ionic_strength_150_mM", "expected_direction": "lower_retention", "evidence_class": "FITTED"},
          "decision_policy": {"version": "rescue.policy.v1", "pareto_status": "NON_DOMINATED"},
          "provenance": {"parent_candidate_id": "BF-018", "structure_source": "sample-buyer-model-BF-018", "mutation_engine_version": "single-substitution.v1"},
          "falsifier": "H:W99Y does not move paired HIC lower than the parent or fails a declared binding, stability, charge, chemistry, disulfide, or protected-position guard.",
          "decision_trace": ["observed_HIC_failure_routed", "4313_single_substitutions_enumerated", "168_legal_edits", "hard_guards_pass", "non_dominated", "binding_guard_required", "propose"]
        },
        {
          "proposal_id": "BF-RES-401-P2",
          "recommendation_role": "ALTERNATIVE",
          "decision": {"state": "PROPOSE", "reason": "non_dominated_alternative_tradeoff"},
          "edit": {"chain": "H", "position": 99, "from": "W", "to": "S", "region": "H3"},
          "responsible_residues": ["H:W99"],
          "parent_vector": {
            "hydrophobic_surface_drive": {"value": 24.9, "unit": "kJ/mol", "evidence_class": "DERIVED", "structure_source": "sample-buyer-model-BF-018"},
            "charge_state": {"value": 1.1, "unit": "e", "pH": 6.0, "evidence_class": "DERIVED"},
            "chemical_sites": {"site_ids": [], "evidence_class": "CONVENTIONAL"},
            "stability_guard_sequence": {"value": 0.0, "unit": "dimensionless", "evidence_class": "EMPIRICAL"},
            "stability_guard_structure": {"value": 0.0, "unit": "dimensionless", "state": "PASS", "evidence_class": "EMPIRICAL", "structure_source": "sample-buyer-model-BF-018"}
          },
          "mutant_vector": {
            "hydrophobic_surface_drive": {"value": 18.1, "unit": "kJ/mol", "evidence_class": "DERIVED", "structure_source": "sample-buyer-model-BF-018"},
            "charge_state": {"value": 1.1, "unit": "e", "pH": 6.0, "evidence_class": "DERIVED"},
            "chemical_sites": {"site_ids": [], "evidence_class": "CONVENTIONAL"},
            "stability_guard_sequence": {"value": -0.11, "unit": "dimensionless", "evidence_class": "EMPIRICAL"},
            "stability_guard_structure": {"value": 0.0, "unit": "dimensionless", "state": "PASS", "evidence_class": "EMPIRICAL", "structure_source": "sample-buyer-model-BF-018"}
          },
          "delta_vector": {
            "hydrophobic_surface_drive": {"value": -6.8, "unit": "kJ/mol", "direction": "DESIRED", "evidence_class": "DERIVED"},
            "charge_state": {"value": 0.0, "unit": "e", "pH": 6.0, "evidence_class": "DERIVED"},
            "chemical_sites": {"added": [], "removed": [], "evidence_class": "CONVENTIONAL"},
            "stability_guard_sequence": {"value": -0.11, "unit": "dimensionless", "evidence_class": "EMPIRICAL", "direction_of_desirability": "higher_is_better", "tradeoff": "ADVERSE"},
            "stability_guard_structure": {"value": 0.0, "unit": "dimensionless", "state": "PASS", "evidence_class": "EMPIRICAL"}
          },
          "component_coverage": {"positive_charge_texture": "NOT_LICENSED_FOR_HIC_RESCUE", "negative_charge_texture": "NOT_LICENSED_FOR_HIC_RESCUE"},
          "hard_guards": {"protected_positions": "PASS", "disulfides": "PASS", "forbidden_motifs": "PASS"},
          "new_liabilities": [],
          "binding_guard_required": true,
          "required_binding_assay": "buyer_binding_or_potency_assay",
          "applicability": {"state": "APPLICABLE", "out_of_domain": false},
          "uncertainty": {"state": "MODERATE", "drivers": ["assay_mapping_uncertainty"]},
          "observation_model": {"assay": "HIC", "mapping_version": "hic.observation.v1", "conditions": "pH_6.0_ionic_strength_150_mM", "expected_direction": "lower_retention", "evidence_class": "FITTED"},
          "decision_policy": {"version": "rescue.policy.v1", "pareto_status": "NON_DOMINATED"},
          "provenance": {"parent_candidate_id": "BF-018", "structure_source": "sample-buyer-model-BF-018", "mutation_engine_version": "single-substitution.v1"},
          "falsifier": "H:W99S does not move paired HIC lower than the parent or fails a declared binding, stability, charge, chemistry, disulfide, or protected-position guard.",
          "decision_trace": ["observed_HIC_failure_routed", "4313_single_substitutions_enumerated", "168_legal_edits", "hard_guards_pass", "non_dominated", "binding_guard_required", "propose"]
        },
        {
          "proposal_id": "BF-RES-401-P3",
          "recommendation_role": "ALTERNATIVE",
          "decision": {"state": "PROPOSE", "reason": "non_dominated_alternative_tradeoff"},
          "edit": {"chain": "L", "position": 94, "from": "F", "to": "Y", "region": "L3"},
          "responsible_residues": ["L:F94"],
          "parent_vector": {
            "hydrophobic_surface_drive": {"value": 24.9, "unit": "kJ/mol", "evidence_class": "DERIVED", "structure_source": "sample-buyer-model-BF-018"},
            "charge_state": {"value": 1.1, "unit": "e", "pH": 6.0, "evidence_class": "DERIVED"},
            "chemical_sites": {"site_ids": [], "evidence_class": "CONVENTIONAL"},
            "stability_guard_sequence": {"value": 0.0, "unit": "dimensionless", "evidence_class": "EMPIRICAL"},
            "stability_guard_structure": {"value": 0.0, "unit": "dimensionless", "state": "PASS", "evidence_class": "EMPIRICAL", "structure_source": "sample-buyer-model-BF-018"}
          },
          "mutant_vector": {
            "hydrophobic_surface_drive": {"value": 21.8, "unit": "kJ/mol", "evidence_class": "DERIVED", "structure_source": "sample-buyer-model-BF-018"},
            "charge_state": {"value": 1.1, "unit": "e", "pH": 6.0, "evidence_class": "DERIVED"},
            "chemical_sites": {"site_ids": [], "evidence_class": "CONVENTIONAL"},
            "stability_guard_sequence": {"value": 0.08, "unit": "dimensionless", "evidence_class": "EMPIRICAL"},
            "stability_guard_structure": {"value": 0.0, "unit": "dimensionless", "state": "PASS", "evidence_class": "EMPIRICAL", "structure_source": "sample-buyer-model-BF-018"}
          },
          "delta_vector": {
            "hydrophobic_surface_drive": {"value": -3.1, "unit": "kJ/mol", "direction": "DESIRED", "evidence_class": "DERIVED"},
            "charge_state": {"value": 0.0, "unit": "e", "pH": 6.0, "evidence_class": "DERIVED"},
            "chemical_sites": {"added": [], "removed": [], "evidence_class": "CONVENTIONAL"},
            "stability_guard_sequence": {"value": 0.08, "unit": "dimensionless", "evidence_class": "EMPIRICAL", "direction_of_desirability": "higher_is_better", "tradeoff": "DESIRED"},
            "stability_guard_structure": {"value": 0.0, "unit": "dimensionless", "state": "PASS", "evidence_class": "EMPIRICAL"}
          },
          "component_coverage": {"positive_charge_texture": "NOT_LICENSED_FOR_HIC_RESCUE", "negative_charge_texture": "NOT_LICENSED_FOR_HIC_RESCUE"},
          "hard_guards": {"protected_positions": "PASS", "disulfides": "PASS", "forbidden_motifs": "PASS"},
          "new_liabilities": [],
          "binding_guard_required": true,
          "required_binding_assay": "buyer_binding_or_potency_assay",
          "applicability": {"state": "APPLICABLE", "out_of_domain": false},
          "uncertainty": {"state": "MODERATE", "drivers": ["assay_mapping_uncertainty"]},
          "observation_model": {"assay": "HIC", "mapping_version": "hic.observation.v1", "conditions": "pH_6.0_ionic_strength_150_mM", "expected_direction": "lower_retention", "evidence_class": "FITTED"},
          "decision_policy": {"version": "rescue.policy.v1", "pareto_status": "NON_DOMINATED"},
          "provenance": {"parent_candidate_id": "BF-018", "structure_source": "sample-buyer-model-BF-018", "mutation_engine_version": "single-substitution.v1"},
          "falsifier": "L:F94Y does not move paired HIC lower than the parent or fails a declared binding, stability, charge, chemistry, disulfide, or protected-position guard.",
          "decision_trace": ["observed_HIC_failure_routed", "4313_single_substitutions_enumerated", "168_legal_edits", "hard_guards_pass", "non_dominated", "binding_guard_required", "propose"]
        }
      ],
      "validation_controls": [
        {"control_id": "BF-RES-401-C1", "experimental_role": "NEUTRAL_CONTROL", "selection_rule": "legal_single_substitution_with_near_zero_target_delta_and_matched_guard_burden", "paired_assay": "HIC", "counted_as_recommendation": false},
        {"control_id": "BF-RES-401-C2", "experimental_role": "ADVERSE_CONTROL", "selection_rule": "legal_single_substitution_with_opposite_target_delta_and_matched_guard_burden", "paired_assay": "HIC", "counted_as_recommendation": false}
      ],
      "falsifier": "Selected negative target-delta edits fail to outperform matched neutral and adverse controls on paired HIC, or a proposed edit breaches a buyer-defined guard.",
      "decision_trace": ["observed_HIC_failure_routed", "4313_single_substitutions_enumerated", "168_legal_edits", "three_non_dominated_proposals", "matched_controls_attached", "propose"]
    },
    {
      "case_id": "BF-RES-226",
      "candidate_id": "BF-226",
      "observed_failure": {"assay": "MET_OXIDATION", "protocol_id": "sample-oxidation-protocol.v1", "value": 18.0, "unit": "percent", "evidence_class": "EMPIRICAL", "threshold": 10.0, "threshold_evidence_class": "CONVENTIONAL", "named_site": "H:M34"},
      "routed_axis": "chemical_sites",
      "applicability": {"state": "REQUIRES_STRUCTURE", "reason": "shielding_route_needs_structure_context", "out_of_domain": false},
      "uncertainty": {"state": "NOT_ESTIMATED", "drivers": ["structure_not_supplied"]},
      "legal_search": {"enumeration": "NOT_STARTED", "enumerated_count": 0, "legal_mutation_count": 0, "non_dominated_count": 0},
      "state": "NEEDS_STRUCTURE",
      "proposals": [],
      "required_input": {"type": "ADMISSIBLE_STRUCTURE", "reason": "named_site_shielding_requires_exposure_context"},
      "binding_requirement": {"required": false, "reason": "no_proposal_generated"},
      "falsifier": "A supplied admissible structure does not resolve site exposure or yields no legal guarded edit.",
      "decision_trace": ["oxidation_failure_routed", "structure_required", "search_not_started", "needs_structure"]
    },
    {
      "case_id": "BF-RES-118",
      "candidate_id": "BF-118",
      "observed_failure": {"assay": "HIC", "protocol_id": "sample-hic-protocol.v1", "value": null, "unit": "min", "evidence_class": "UNSUPPORTED", "threshold": 11.0, "threshold_evidence_class": "CONVENTIONAL"},
      "routed_axis": null,
      "applicability": {"state": "MISSING_ASSAY", "reason": "observed_value_absent", "out_of_domain": false},
      "uncertainty": {"state": "NOT_ESTIMATED", "drivers": ["observed_value_absent"]},
      "legal_search": {"enumeration": "NOT_STARTED", "enumerated_count": 0, "legal_mutation_count": 0, "non_dominated_count": 0},
      "state": "NEEDS_ASSAY",
      "proposals": [],
      "required_assay": {"assay": "HIC", "protocol_id": "sample-hic-protocol.v1", "reason": "observed_value_absent"},
      "binding_requirement": {"required": false, "reason": "no_proposal_generated"},
      "falsifier": "A completed assay does not meet the declared failure criterion.",
      "decision_trace": ["observed_value_absent", "search_not_started", "assay_requested", "needs_assay"]
    },
    {
      "case_id": "BF-RES-903",
      "candidate_id": "BF-903",
      "observed_failure": {"assay": "SPR_KD", "protocol_id": "sample-spr-protocol.v1", "value": 45.0, "unit": "nM", "evidence_class": "EMPIRICAL", "threshold": 10.0, "threshold_evidence_class": "CONVENTIONAL"},
      "routed_axis": null,
      "applicability": {"state": "OUT_OF_SCOPE", "reason": "affinity_loss_not_modeled", "out_of_domain": true},
      "uncertainty": {"state": "NOT_ESTIMATED", "drivers": ["unsupported_failure_axis"]},
      "legal_search": {"enumeration": "NOT_STARTED", "enumerated_count": 0, "legal_mutation_count": 0, "non_dominated_count": 0},
      "state": "ABSTAIN",
      "proposals": [],
      "binding_requirement": {"required": true, "assay": "buyer_affinity_model_or_experiment", "reason": "affinity_failure"},
      "falsifier": "No rescue statement is made for this failure class without a buyer affinity model or experiment.",
      "decision_trace": ["affinity_failure_identified", "failure_axis_out_of_scope", "search_not_started", "abstain"]
    }
  ],
  "provenance": {
    "engine_version": "biofold-antibody-1.0.0",
    "physical_object_version": "physical-vector.v1",
    "observation_versions": ["hic.observation.v1", "chemical-site.observation.v1"],
    "mutation_engine_version": "single-substitution.v1",
    "policy_version": "rescue.policy.v1",
    "hash_scope": {"input": "sha256_of_UTF8_JSON.stringify_request", "output": "sha256_of_UTF8_JSON.stringify_response_omitting_provenance.output_hash_and_provenance.served_at"},
    "input_hash": "sha256:9c67d5c9f59724d49f548c19300c7c2a52b87db91fb37478941df5e2038cb6e6",
    "output_hash": "sha256:1bf17c92f0d99b3c80f089f48319a7637f3db95bdebc370ce84e96a4cb135422",
    "served_at": "2026-07-10T12:05:00Z"
  }
}

Decision trace and evidence architecture

Each decision record includes its evidence and policy trace.

Physical outputs, assay observations, and buyer policy remain separately versioned. A policy change never rewrites a molecular value, and an assay update never changes a hard constraint.

Request identity

Library, candidate, lineage, paired chain hashes, assay protocol, buyer constraints, and missing-value policy.

Validity and hard gates

Sequence validity, chain mapping, protected residues, disulfides, forbidden amino acids, and forbidden motifs.

Applicability

Coverage, required structure, assay-condition match, out-of-distribution state, uncertainty drivers, and abstention reason.

Physical vector

Named quantities, units, responsible residues, assumptions, component versions, and complete mutant recomputation.

Assay observation

Mapping version, applicable cohort and conditions, direction, estimate when licensed, uncertainty, and source record.

Decision policy

Pareto tier, declared tie-break, budget, lineage cap, diversity contribution, state, and deterministic reason.

Rescue search

Observed failure route, complete single-substitution count, legal count, hard rejections, and non-dominated set.

Experimental handoff

Target and guard deltas, new liabilities, binding requirement, matched controls, falsifier, policy hash, and output hash.

Physical status

Definition, unit, assumptions, responsible residues, component version

Observation status

Assay mapping, cohort, conditions, direction, uncertainty, version

Policy status

Hard gates, Pareto tier, tie-break, diversity rule, decision reason

Applicability

Coverage, structural requirements, out-of-distribution state, abstention

Intervention record

Enumerated count, legal count, full mutant vector, dominated alternatives

Guard record

Charge, chemistry, stability, protected positions, binding requirement

Provenance

Request ID, engine and policy versions, input hash, output hash, served time

Falsification

Matched controls, failure criterion, expected observation, stop condition

BioFold access

Define the decision your next round must support.

Start with a paired VH/VL library, the assay protocol, synthesis budget, protected positions, and the decision criteria your team already uses.

BioFold returns the shortlist, the failure routes, the legal rescue set, the experimental guards, and a shareable decision trace.

Discuss an antibody program Review the sample report Inspect the integration contract