# Techniques that can contribute evidence. Every technique used in evidence must appear here.
#
# basis:      observed  - the technique resolves a structure directly (X-ray, cryo-EM, microED, neutron, NMR structure)
#             inferred  - the technique reports indirect constraints; any model is fitted to them
# prediction: true      - the source is a computed prediction, not an experiment (shown with a badge on the site)
# tier:       1 ingest first (structured repository, searchable by UniProt); 2 added value (raw traces scattered); 3 reported values only; null for predictions
# raw_location / raw_format: where raw or near-raw data live and in what format. Raw data are indexed by pointer, never hosted.
# resolution_class: the spatial or population scale the technique speaks to
# observables: the observable types evidence may report for this technique
techniques:
  # ---- structures
  - id: xray
    name: X-ray crystallography
    category: structure
    basis: observed
    prediction: false
    tier: 1
    raw_location: "PDB (structure factors); diffraction images at SBGrid Data Bank / IRRMC"
    raw_format: "mmCIF, diffraction images"
    resolution_class: atomic
    observables: [structure, resolution, b_factor, disorder_region]
    description: Electron density from diffraction of protein crystals. Conformations are crystal-packing dependent.
  - id: cryoem
    name: Cryo-electron microscopy
    category: structure
    basis: observed
    prediction: false
    tier: 1
    raw_location: "EMDB (maps, half-maps); EMPIAR (micrographs, particles)"
    raw_format: "MRC, STAR"
    resolution_class: atomic
    observables: [structure, resolution, class_population, disorder_region]
    description: Single-particle or tomographic reconstruction. Class populations from classification are inferred from particle counts.
  - id: xray_time_resolved
    name: Time-resolved and multi-temperature X-ray
    category: structure
    basis: observed
    prediction: false
    tier: 1
    raw_location: "PDB (structure factors); diffraction images at SBGrid Data Bank / IRRMC"
    raw_format: "mmCIF, diffraction images"
    resolution_class: atomic
    observables: [structure, resolution, b_factor, occupancy, alternate_conformation, time_delay, temperature_series]
    description: Pump-probe, serial and multi-temperature crystallography. Resolves alternate conformations and their occupancies, and structural change over time. Conformations remain crystal-packing dependent.
  - id: cryoem_heterogeneity
    name: Cryo-EM heterogeneity analysis
    category: structure
    basis: observed
    prediction: false
    tier: 1
    raw_location: "EMDB (maps, half-maps); EMPIAR (micrographs, particles)"
    raw_format: "MRC, STAR"
    resolution_class: atomic
    observables: [structure, resolution, class_population, conformational_landscape]
    description: 3D classification, variability and manifold analysis of one sample. Gives several states and their relative populations from particle counts; populations are inferred, the class maps are observed.
  - id: microed
    name: Microcrystal electron diffraction
    category: structure
    basis: observed
    prediction: false
    tier: 1
    raw_location: "PDB; EMPIAR for diffraction movies"
    raw_format: "mmCIF, diffraction images"
    resolution_class: atomic
    observables: [structure, resolution]
    description: Electron diffraction from nanocrystals.
  - id: neutron
    name: Neutron diffraction
    category: structure
    basis: observed
    prediction: false
    tier: 1
    raw_location: "PDB (structure factors)"
    raw_format: "mmCIF"
    resolution_class: atomic
    observables: [structure, resolution]
    description: Neutron diffraction from crystals; sensitive to hydrogen and deuterium positions.

  # ---- solution ensembles
  - id: nmr_structure
    name: NMR structure determination
    category: solution_ensemble
    basis: observed
    prediction: false
    tier: 1
    raw_location: "BMRB (restraints); PDB"
    raw_format: "NMR-STAR, mmCIF"
    resolution_class: residue
    observables: [structure, restraint_count]
    description: Ensemble of structures calculated from NOE, RDC and other restraints. Each member is a model consistent with restraints.
  - id: nmr_dynamics
    name: NMR relaxation and dispersion
    category: solution_ensemble
    basis: inferred
    prediction: false
    tier: 1
    raw_location: "BMRB; BMRbig for raw FIDs"
    raw_format: "NMR-STAR, FIDs"
    resolution_class: residue
    observables: [relaxation_rate, exchange_rate, chemical_shift_difference, population, protection_factor, residual_dipolar_coupling, paramagnetic_relaxation_enhancement, disorder_region]
    description: Relaxation (R1, R2, NOE), relaxation dispersion (CPMG, R1rho), RDCs and PREs report on exchange between states and their populations and rates.
  - id: nmr_shifts
    name: NMR chemical shift assignment
    category: solution_ensemble
    basis: inferred
    prediction: false
    tier: 1
    raw_location: "BMRB"
    raw_format: "NMR-STAR"
    resolution_class: residue
    observables: [chemical_shift, secondary_structure_propensity, disorder_region]
    description: Assigned chemical shifts. Report on secondary structure, folding and disorder per residue; states are inferred from them.
  - id: saxs_sans
    name: SAXS / SANS
    category: solution_ensemble
    basis: inferred
    prediction: false
    tier: 1
    raw_location: "SASBDB"
    raw_format: "scattering curves"
    resolution_class: global
    observables: [radius_of_gyration, distance_distribution, shape_parameter, disorder_region, structure]
    description: Small-angle scattering profiles. Models are fitted to the scattering curve and are not unique.
  - id: ped_ensemble
    name: Disordered-protein ensemble
    category: solution_ensemble
    basis: inferred
    prediction: false
    tier: 1
    raw_location: "PED"
    raw_format: "ensembles (PDB/mmCIF)"
    resolution_class: residue
    observables: [structure, radius_of_gyration, disorder_region, population]
    description: Ensembles of IDPs and IDRs fitted to NMR, SAXS and other restraints (PED). Members are models consistent with the data, not resolved structures.
  - id: epr_deer
    name: EPR / DEER
    category: solution_ensemble
    basis: inferred
    prediction: false
    tier: 2
    raw_location: "No repository; sometimes Zenodo / Figshare"
    raw_format: "time-domain traces"
    resolution_class: residue
    observables: [distance, distance_distribution, disorder_region]
    description: Spin-label distance distributions between labelled residues.
  - id: cd
    name: Circular dichroism
    category: solution_ensemble
    basis: inferred
    prediction: false
    tier: 1
    raw_location: "PCDDB"
    raw_format: "spectra"
    resolution_class: global
    observables: [secondary_structure_fraction, cd_signal, melting_temperature, disorder_region]
    description: Far-UV and near-UV CD. Secondary-structure fractions depend on the deconvolution method.
  - id: ftir_raman
    name: FTIR / Raman spectroscopy
    category: solution_ensemble
    basis: inferred
    prediction: false
    tier: 3
    raw_location: "Paper only"
    raw_format: "reported values"
    resolution_class: global
    observables: [secondary_structure_fraction, band_shift, disorder_region]
    description: Vibrational spectroscopy of backbone amide bands and side chains.
  - id: fluorescence
    name: Fluorescence spectroscopy
    category: solution_ensemble
    basis: inferred
    prediction: false
    tier: 3
    raw_location: "Paper only"
    raw_format: "reported values"
    resolution_class: global
    observables: [emission_shift, lifetime, anisotropy, quenching_constant, disorder_region]
    description: Intrinsic or extrinsic fluorescence, lifetimes and anisotropy.
  - id: ensemble_fret
    name: Ensemble FRET
    category: solution_ensemble
    basis: inferred
    prediction: false
    tier: 3
    raw_location: "Paper only"
    raw_format: "reported values"
    resolution_class: residue
    observables: [fret_efficiency, distance, disorder_region]
    description: Bulk FRET efficiency between donor and acceptor labels.

  # ---- single molecule
  - id: smfret
    name: Single-molecule FRET
    category: single_molecule
    basis: inferred
    prediction: false
    tier: 2
    raw_location: "Zenodo / Figshare, unindexed (DataCite)"
    raw_format: "Photon-HDF5 timestamps; TIRF intensity traces"
    resolution_class: single_molecule
    observables: [fret_efficiency, population, transition_rate, dwell_time, disorder_region]
    description: FRET efficiency histograms and dwell times from individual molecules.
  - id: force_spectroscopy
    name: Force spectroscopy
    category: single_molecule
    basis: inferred
    prediction: false
    tier: 2
    raw_location: "Linked from SMASH-BIO"
    raw_format: "TraceSet sidecar over HDF5 / TDMS"
    resolution_class: single_molecule
    observables: [unfolding_force, rupture_force, unfolding_rate, contour_length_increment, free_energy_difference, refolding_force, unbinding_force, adhesion_force, contour_length, persistence_length, folding_free_energy, distance_to_transition_state, folding_rate, rate_constant_zero_force, step_size, stall_force, velocity, dwell_time, bond_lifetime, loading_rate, elastic_modulus, molecular_stiffness, equilibrium_force, overstretching_force, torque, study_record]
    description: Optical or magnetic tweezers and AFM-based single-molecule force spectroscopy, including SMASH-BIO records.
  - id: hs_afm
    name: High-speed AFM imaging
    category: single_molecule
    basis: inferred
    prediction: false
    tier: 2
    raw_location: "BioImage Archive, scattered"
    raw_format: "image stacks"
    resolution_class: single_molecule
    observables: [shape_parameter, population, dwell_time]
    description: Time-resolved topographic imaging of surface-bound molecules.
  - id: nanopore
    name: Nanopore
    category: single_molecule
    basis: inferred
    prediction: false
    tier: 2
    raw_location: "Scattered (DataCite)"
    raw_format: "current traces"
    resolution_class: single_molecule
    observables: [current_blockade, dwell_time, population]
    description: Current blockade signatures from molecules translocating or trapped in a pore.
  - id: iscat
    name: Interferometric scattering (iSCAT)
    category: single_molecule
    basis: inferred
    prediction: false
    tier: 3
    raw_location: "Paper only"
    raw_format: "reported values"
    resolution_class: single_molecule
    observables: [mass, population, dwell_time]
    description: Label-free interferometric imaging of single molecules and complexes.
  - id: mass_photometry
    name: Mass photometry
    category: single_molecule
    basis: inferred
    prediction: false
    tier: 3
    raw_location: "Paper only"
    raw_format: "reported values"
    resolution_class: single_molecule
    observables: [mass, population]
    description: Single-molecule mass distributions from interferometric contrast.

  # ---- mass spectrometry
  - id: hdx_ms
    name: Hydrogen-deuterium exchange MS
    category: mass_spectrometry
    basis: inferred
    prediction: false
    tier: 2
    raw_location: "PRIDE (community format, low uptake)"
    raw_format: "uptake tables + raw MS"
    resolution_class: residue
    observables: [exchange_rate, protection_factor, deuterium_uptake, disorder_region]
    description: Deuterium uptake by peptide and residue region. Protection is interpreted through a structural model.
  - id: xl_ms
    name: Crosslinking MS
    category: mass_spectrometry
    basis: inferred
    prediction: false
    tier: 2
    raw_location: "PRIDE / jPOST"
    raw_format: "mzIdentML + raw"
    resolution_class: residue
    observables: [crosslink_distance]
    description: Distance restraints from chemical crosslinks identified by MS.
  - id: native_ms
    name: Native and ion-mobility MS
    category: mass_spectrometry
    basis: inferred
    prediction: false
    tier: 3
    raw_location: "Paper only"
    raw_format: "reported values"
    resolution_class: global
    observables: [collision_cross_section, population, mass, disorder_region]
    description: Gas-phase conformers and their collision cross sections. Gas-phase conformations may differ from solution.
  - id: limited_proteolysis
    name: Limited proteolysis
    category: mass_spectrometry
    basis: inferred
    prediction: false
    tier: 3
    raw_location: "PRIDE (LiP-MS deposits may move it to Tier 2)"
    raw_format: "reported values"
    resolution_class: domain
    observables: [protease_susceptibility, population, disorder_region]
    description: Cleavage patterns that report on accessible regions. Read-out is by gel or MS.
  - id: footprinting
    name: Covalent footprinting
    category: mass_spectrometry
    basis: inferred
    prediction: false
    tier: 3
    raw_location: "Paper only"
    raw_format: "reported values"
    resolution_class: residue
    observables: [labelling_rate, protection_factor]
    description: Hydroxyl radical, SAP or other covalent labelling of solvent-accessible residues.

  # ---- stability and shape
  - id: denaturation
    name: Chemical and thermal denaturation
    category: stability
    basis: inferred
    prediction: false
    tier: 3
    raw_location: "ProThermDB"
    raw_format: "reported values"
    resolution_class: global
    observables: [delta_g, melting_temperature, m_value]
    description: Equilibrium unfolding monitored by any probe. Two-state fits are assumed unless stated.
  - id: dsc
    name: Differential scanning calorimetry
    category: stability
    basis: inferred
    prediction: false
    tier: 3
    raw_location: "ProThermDB"
    raw_format: "reported values"
    resolution_class: global
    observables: [melting_temperature, enthalpy, heat_capacity_change]
    description: Heat capacity profiles of thermal unfolding.
  - id: auc
    name: Analytical ultracentrifugation
    category: stability
    basis: inferred
    prediction: false
    tier: 3
    raw_location: "Paper only"
    raw_format: "reported values"
    resolution_class: global
    observables: [sedimentation_coefficient, population, disorder_region]
    description: Sedimentation velocity and equilibrium; reports on oligomeric state and shape.
  - id: dls
    name: Dynamic light scattering
    category: stability
    basis: inferred
    prediction: false
    tier: 3
    raw_location: "Paper only"
    raw_format: "reported values"
    resolution_class: global
    observables: [hydrodynamic_radius, population, disorder_region]
    description: Hydrodynamic radius distributions.

  - id: gel_electrophoresis
    name: Gel electrophoresis (anomalous mobility)
    category: stability
    basis: inferred
    prediction: false
    tier: 3
    raw_location: "Paper only"
    raw_format: "reported values"
    resolution_class: global
    observables: [gel_mobility, disorder_region]
    description: SDS-PAGE or native PAGE mobility. Anomalous mobility is used as indirect evidence of disorder.
  - id: sec
    name: Size-exclusion chromatography
    category: stability
    basis: inferred
    prediction: false
    tier: 3
    raw_location: "Paper only"
    raw_format: "reported values"
    resolution_class: global
    observables: [hydrodynamic_radius, disorder_region]
    description: Elution volume against standards gives an apparent size; expanded disordered chains elute early.

  # ---- in cell
  - id: in_cell_nmr
    name: In-cell NMR
    category: in_cell
    basis: inferred
    prediction: false
    tier: 3
    raw_location: "Paper only"
    raw_format: "reported values"
    resolution_class: residue
    observables: [chemical_shift_difference, population]
    description: NMR inside living cells.
  - id: flim_fret
    name: FLIM-FRET in cells
    category: in_cell
    basis: inferred
    prediction: false
    tier: 3
    raw_location: "Paper only"
    raw_format: "reported values"
    resolution_class: residue
    observables: [fret_efficiency, lifetime]
    description: Fluorescence lifetime imaging of FRET in cells.
  - id: in_cell_lip
    name: In-cell limited proteolysis
    category: in_cell
    basis: inferred
    prediction: false
    tier: 3
    raw_location: "PRIDE"
    raw_format: "mzIdentML + raw"
    resolution_class: domain
    observables: [protease_susceptibility]
    description: Limited proteolysis of proteins in lysate or intact cells.

  # ---- nucleic-acid probing (RNA and DNA). Per-nucleotide profiles are stored as a profile, not one value.
  - id: shape
    name: SHAPE, SHAPE-MaP and icSHAPE
    category: nucleic_acid_probing
    basis: inferred
    prediction: false
    tier: 1
    raw_location: "RMDB (curated profiles); RASP (transcriptome-wide); reads in SRA / GEO"
    raw_format: "RDAT, reactivity tables; FASTQ"
    resolution_class: residue
    observables: [reactivity_profile, population, secondary_structure, disorder_region]
    description: 2'-hydroxyl acylation reactivity per nucleotide, in vitro or in cells. Reports flexibility and pairing; structures are inferred by folding algorithms constrained by the profile.
  - id: dms_mapseq
    name: DMS-MaPseq and DMS-seq
    category: nucleic_acid_probing
    basis: inferred
    prediction: false
    tier: 1
    raw_location: "RMDB, RASP, SRA / GEO"
    raw_format: "RDAT; FASTQ"
    resolution_class: residue
    observables: [reactivity_profile, population, secondary_structure]
    description: Dimethyl sulfate modification of A and C. Alternative structures can be resolved by clustering (DREEM, DRACO); each cluster is a candidate state with a population.
  - id: duplex_crosslinking
    name: Duplex crosslinking (PARIS, SPLASH, COMRADES)
    category: nucleic_acid_probing
    basis: inferred
    prediction: false
    tier: 2
    raw_location: "SRA / GEO, scattered"
    raw_format: "FASTQ, chimeric-read tables"
    resolution_class: residue
    observables: [crosslink_chimera, population]
    description: Psoralen crosslinking and proximity ligation capture base-paired helices, including long-range and alternative helices in cells.
  - id: mutate_and_map
    name: Mutate-and-map and M2-seq
    category: nucleic_acid_probing
    basis: inferred
    prediction: false
    tier: 2
    raw_location: "RMDB"
    raw_format: "RDAT"
    resolution_class: residue
    observables: [reactivity_profile, pairing_partner]
    description: Chemical mapping of single and double mutants to identify pairing partners and validate helices.
  - id: na_footprinting
    name: Hydroxyl-radical and nuclease footprinting
    category: nucleic_acid_probing
    basis: inferred
    prediction: false
    tier: 2
    raw_location: "RMDB, scattered"
    raw_format: "reactivity tables, gel images"
    resolution_class: residue
    observables: [reactivity_profile, protection_factor]
    description: Solvent accessibility, tertiary packing and protein contacts of nucleic acids.
  - id: uv_melting
    name: Optical (UV) melting
    category: nucleic_acid_probing
    basis: inferred
    prediction: false
    tier: 3
    raw_location: "Values in papers"
    raw_format: "reported values"
    resolution_class: global
    observables: [melting_temperature, delta_g, enthalpy]
    description: Absorbance melting of helices and G-quadruplexes; thermodynamic parameters depend on a two-state model.
  - id: native_gel_mobility
    name: Native gel mobility
    category: nucleic_acid_probing
    basis: inferred
    prediction: false
    tier: 3
    raw_location: "Papers"
    raw_format: "reported values"
    resolution_class: global
    observables: [gel_mobility, population]
    description: Electrophoretic mobility under native conditions as a read-out of compaction and alternative folds.
  - id: na_secondary_prediction
    name: Secondary-structure prediction (ViennaRNA, RNAstructure)
    category: computational
    basis: inferred
    prediction: true
    tier: null
    raw_location: "Generated"
    raw_format: "dot-bracket"
    resolution_class: residue
    observables: [secondary_structure, free_energy_difference, population]
    description: Minimum free-energy and ensemble predictions of base pairing. Predictions, not measurements.
  - id: rfam_covariation
    name: Comparative sequence analysis (Rfam covariance model)
    category: computational
    basis: inferred
    prediction: true
    tier: null
    raw_location: "Rfam"
    raw_format: "Stockholm alignment (SS_cons), covariance model"
    resolution_class: residue
    observables: [family_coverage, secondary_structure]
    description: Membership of an RNA family by covariance-model search, and the family's consensus secondary structure inferred from covariation across homologs. Evolutionary inference, not a measurement on this molecule.
  - id: na_3d_prediction
    name: Nucleic-acid 3D structure prediction
    category: computational
    basis: inferred
    prediction: true
    tier: null
    raw_location: "Generated"
    raw_format: "PDB, mmCIF"
    resolution_class: atomic
    observables: [structure, plddt]
    description: Predicted 3D models of RNA or DNA. Predictions, not measurements.

  # ---- computational (predictions, flagged on the site)
  - id: integrative
    name: Integrative modelling
    category: computational
    basis: inferred
    prediction: false
    tier: 1
    raw_location: "PDB-IHM"
    raw_format: "mmCIF/IHM"
    resolution_class: atomic
    observables: [structure]
    description: Models built by combining several kinds of experimental restraints (PDB-IHM). Experiment-driven, but the structure is fitted, not resolved.
  - id: af_prediction
    name: AlphaFold prediction
    category: computational
    basis: inferred
    prediction: true
    tier: null
    raw_location: "AlphaFold DB"
    raw_format: "mmCIF, PAE JSON"
    resolution_class: atomic
    observables: [structure, plddt]
    description: Single predicted structure from AlphaFold DB, with per-residue confidence (pLDDT). A prediction, not a measurement.
  - id: md
    name: Molecular dynamics
    category: computational
    basis: inferred
    prediction: true
    tier: 1
    raw_location: "MDDB/MDposit, ATLAS, GPCRmd"
    raw_format: "trajectories"
    resolution_class: atomic
    observables: [rmsd, population, free_energy_difference, transition_rate, disorder_region, trajectory]
    description: Simulation trajectories. Sampling and force-field choices are assumptions.
  - id: msm
    name: Markov state model
    category: computational
    basis: inferred
    prediction: true
    tier: 1
    raw_location: "MDDB/MDposit"
    raw_format: "trajectories"
    resolution_class: global
    observables: [population, transition_rate]
    description: Kinetic models built from simulation data.
  - id: af_ensemble
    name: AlphaFold-based ensemble
    category: computational
    basis: inferred
    prediction: true
    tier: null
    raw_location: "Paper / DataCite"
    raw_format: "mmCIF"
    resolution_class: atomic
    observables: [population, structure]
    description: Ensembles generated from AlphaFold-style predictors. Predictions, not measurements.