{
    "app": "Ascorbate Deficiency Long-Read Analyzer",
    "version": "0.1.7-hardening",
    "job_id": "adla_20260707_065700_a7ac71b8",
    "created_at": "2026-07-07T06:57:00+00:00",
    "reference_build": "GRCh38",
    "disclaimer": "Anthropological and educational research use only. ADLA does not diagnose scurvy or vitamin C deficiency; interpret genomic, epigenomic, structural-variant, phasing, workflow-import, microbial/context, and ancient-DNA authentication signals alongside archaeological context, preservation quality, osteological/isotopic evidence, historical diet, contamination controls, damage/authenticity metrics, and biochemical data where available.",
    "input_files": [
        {
            "original_name": "reich_lab_style_demo_auth.json",
            "stored_name": "reich_lab_style_demo_auth.json",
            "stored_path": "/home/u649646827/domains/stellanovaeducation.com/public_html/rc/adla/inc/../uploads/adla_20260707_065700_a7ac71b8/reich_lab_style_demo_auth.json",
            "size_bytes": 1164,
            "sha256": "26bf624b4a00382d7bed80c83dae34d8f8c8bfcd978c52e75ca204600a6e889f",
            "extension": "json",
            "kind": "json"
        }
    ],
    "sample_context": {
        "reference_build": "GRCh38",
        "sample_age_class": "unknown",
        "sample_material": "unknown",
        "sample_type": "",
        "preservation_context": "",
        "archaeological_context": "",
        "osteological_evidence": "",
        "isotopic_evidence": "",
        "dietary_evidence": "",
        "historical_dietary_context": "",
        "environmental_context": "",
        "contamination_controls": "",
        "damage_authenticity_review": "",
        "intergenerational_question": "",
        "notes": "",
        "ascorbate_lab_value": ""
    },
    "qc": [],
    "variants": {
        "known_ascorbate_hits": [],
        "target_region_hits": [],
        "unclassified_target_hits": [],
        "summary": []
    },
    "methylation": {
        "target_region_summaries": [],
        "global_summary": []
    },
    "coverage": {
        "target_region_depths": [],
        "summary": []
    },
    "annotation": {
        "summaries": [],
        "clinvar_target_hits": [],
        "high_impact_target_hits": [],
        "vep_consequence_counts": [],
        "clinvar_significance_counts": []
    },
    "priority": {
        "variant_priorities": [],
        "summary": {
            "prioritized_variant_count": 0,
            "top_score": 0,
            "top_priority_bucket": "none",
            "bucket_counts": [],
            "callability_counts": {
                "callable": 0,
                "low_coverage": 0,
                "unknown": 0
            },
            "ruleset_version": "0.1.7-hardening",
            "boundary": "Anthropological research prioritization only. Scores rank sequencing and authentication findings for review in ancient, historical, modern-intergenerational, or ecological context; they do not diagnose vitamin C deficiency, scurvy, connective-tissue disease, or any medical condition."
        },
        "scoring_policy": {
            "ruleset_name": "ADLA variant prioritization rules",
            "ruleset_version": "0.1.7-hardening",
            "score_range": [
                0,
                100
            ],
            "evidence_classes": [
                "known_ascorbate_transport_literature",
                "target_pathway_location",
                "VEP_consequence_and_impact",
                "ClinVar_assertion_and_review_status",
                "dbSNP_rsID_normalization",
                "sample_variant_support",
                "target_callability",
                "anthropological_context",
                "ancient_or_historical_sample_readiness",
                "ancient_DNA_authentication_report_import",
                "damage_deamination_or_PMD_metric",
                "contamination_estimate_import"
            ],
            "priority_buckets": [
                {
                    "min_score": 75,
                    "label": "very_high_review_priority",
                    "description": "Strong local evidence stack. Review first, confirm coverage/source dates, and interpret only with clinical/biochemical context."
                },
                {
                    "min_score": 55,
                    "label": "high_review_priority",
                    "description": "Multiple supportive evidence classes or one strong annotation class."
                },
                {
                    "min_score": 35,
                    "label": "moderate_review_priority",
                    "description": "Useful research hit requiring annotation/source review."
                },
                {
                    "min_score": 15,
                    "label": "contextual_review",
                    "description": "Contextual pathway or modifier signal; not enough for strong prioritization."
                },
                {
                    "min_score": 0,
                    "label": "low_priority_or_uncurated",
                    "description": "Weak, missing, or uncurated evidence."
                }
            ],
            "boundary": "Anthropological research prioritization only. Scores rank sequencing and authentication findings for review in ancient, historical, modern-intergenerational, or ecological context; they do not diagnose vitamin C deficiency, scurvy, connective-tissue disease, or any medical condition."
        }
    },
    "anthropological_context": {
        "summary": {
            "sample_age_class": "unknown",
            "sample_material": "unknown",
            "preservation_context": "",
            "anthropological_corroboration_score": 0,
            "score_components": [
                {
                    "component": "unknown_sample_age_penalty",
                    "points": -8,
                    "note": "Sample age class is unknown, reducing anthropological interpretability."
                }
            ],
            "interpretation_mode": "modern_or_unknown_research_context",
            "methylation_mode": "direct_modbase_exploratory_when_metadata_complete"
        },
        "evidence_domains": {
            "genomic_susceptibility": {
                "status": "not_observed_in_uploaded_inputs",
                "summary": "0 curated ascorbate-transporter hit(s); 0 target-window variant(s)."
            },
            "modified_base_or_methylation_signal": {
                "status": "not_available",
                "summary": "0 target methylation/modified-base summary row(s)."
            },
            "ancient_dna_authenticity": {
                "status": "not_required_for_modern_context",
                "summary": "Age class: unknown; material: unknown; imported authentication reports: 0."
            },
            "authentication_imports": {
                "status": "not_imported",
                "summary": "No mapDamage/schmutzi/PMDtools/contamination report imported."
            },
            "osteological_paleopathology": {
                "status": "not_provided",
                "summary": ""
            },
            "isotopic_dietary_context": {
                "status": "not_provided",
                "summary": ""
            },
            "historical_ethnographic_context": {
                "status": "not_provided",
                "summary": ""
            },
            "ecological_or_provisioning_constraint": {
                "status": "not_provided",
                "summary": ""
            },
            "intergenerational_context": {
                "status": "not_specified",
                "summary": ""
            }
        },
        "ancient_sample_readiness": {
            "age_class": "unknown",
            "material": "unknown",
            "requires_damage_profile": false,
            "requires_contamination_estimate": false,
            "contamination_controls_present": false,
            "damage_authenticity_review_present": false,
            "authentication_report_count": 0,
            "authentication_aggregate": {
                "report_count": 0,
                "tools_detected": [],
                "status": "not_imported",
                "has_damage_metric": false,
                "has_contamination_metric": false,
                "has_endogenous_fraction": false,
                "has_pmd_metric": false,
                "max_contamination_percent": null,
                "metrics": [],
                "flags": []
            },
            "fastq_fragment_profiles": [],
            "readiness_status": "not_an_ancient_sample_mode"
        },
        "messages": [
            {
                "level": "scope",
                "message": "ADLA is currently framed for anthropological nutritional-stress research, not medical diagnosis. Interpret sequence-derived findings alongside archaeological, osteological, isotopic, ecological, and historical evidence."
            },
            {
                "level": "gap",
                "message": "No target callability data were provided. Anthropological interpretation should avoid absence claims until coverage/callability is measured across the panel."
            }
        ],
        "raw_context": {
            "reference_build": "GRCh38",
            "sample_age_class": "unknown",
            "sample_material": "unknown",
            "sample_type": "",
            "preservation_context": "",
            "archaeological_context": "",
            "osteological_evidence": "",
            "isotopic_evidence": "",
            "dietary_evidence": "",
            "historical_dietary_context": "",
            "environmental_context": "",
            "contamination_controls": "",
            "damage_authenticity_review": "",
            "intergenerational_question": "",
            "notes": "",
            "ascorbate_lab_value": ""
        },
        "boundary": "ADLA evaluates genomic, modified-base, preservation, and contextual evidence relevant to ascorbate stress and scurvy-like vulnerability in anthropological, historical, ancient-remains, and intergenerational research. It does not diagnose vitamin C deficiency or scurvy."
    },
    "authentication": {
        "summaries": [],
        "aggregate": {
            "report_count": 0,
            "tools_detected": [],
            "status": "not_imported",
            "has_damage_metric": false,
            "has_contamination_metric": false,
            "has_endogenous_fraction": false,
            "has_pmd_metric": false,
            "max_contamination_percent": null,
            "metrics": [],
            "flags": []
        },
        "messages": [],
        "boundary": "Imported ancient-DNA authentication reports support anthropological interpretation only; they do not prove biological deficiency or diagnose disease."
    },
    "tool_profiles": {
        "registry_version": "0.1.6",
        "strategy": "Import-first, worker-compatible profiles. Hostinger web mode parses outputs; CLI/worker mode may execute installed tools where licensing, compute, and environment allow.",
        "profiles": [
            {
                "profile_id": "fastvep",
                "name": "fastVEP annotation profile",
                "category": "annotation",
                "purpose": "Fast local VEP-compatible consequence and supplementary annotation import.",
                "execution_mode": "worker_or_import",
                "import_file_hints": [
                    "fastvep.json",
                    "fastvep.vcf",
                    "CSQ",
                    "ClinVar",
                    "gnomAD"
                ],
                "primary_tools": [
                    {
                        "name": "fastVEP",
                        "purpose": "High-performance Rust variant consequence annotation with VEP-compatible outputs and supplementary database integration.",
                        "license": "Check upstream fastVEP license and bundled database terms before redistribution.",
                        "preferred_local_path": "tools/bin/fastvep",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "ADLA parses fastVEP JSON/VCF-style imports and can use it as a worker annotation profile."
                    },
                    {
                        "name": "bcftools",
                        "purpose": "Local VCF normalization, target slicing, indexing-aware filtering, and annotation transfer from ClinVar/dbSNP VCFs.",
                        "license": "MIT/BSD-style htslib/samtools family; verify upstream version.",
                        "preferred_local_path": "tools/bin/bcftools",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "Primary lightweight engine for offline ClinVar/dbSNP annotation and ADLA target-slice generation."
                    },
                    {
                        "name": "tabix",
                        "purpose": "Index bgzip-compressed VCF/BED annotation files for local random access.",
                        "license": "MIT/BSD-style htslib/samtools family; verify upstream version.",
                        "preferred_local_path": "tools/bin/tabix",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "Required for indexed ClinVar/dbSNP VCF usage."
                    },
                    {
                        "name": "bgzip",
                        "purpose": "Block gzip compression for VCF/BED files that need tabix indexing.",
                        "license": "MIT/BSD-style htslib/samtools family; verify upstream version.",
                        "preferred_local_path": "tools/bin/bgzip",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "Used by annotation prep scripts when normalizing or slicing local reference VCFs."
                    }
                ],
                "tools_available": 0,
                "tool_count": 4,
                "status": "import_ready",
                "notes": "Use as a fast local annotation path; VEP remains a conservative reference path."
            },
            {
                "profile_id": "longhap",
                "name": "LongHap methylation-aware phasing profile",
                "category": "phasing",
                "purpose": "Import or execute haplotype phasing that integrates long-read methylation evidence.",
                "execution_mode": "worker_or_import",
                "import_file_hints": [
                    "longhap",
                    "phased.vcf",
                    "haplotagged",
                    "phase_set"
                ],
                "primary_tools": [
                    {
                        "name": "LongHap",
                        "purpose": "Read-based phasing that integrates native long-read methylation signals with variant calls.",
                        "license": "MIT per upstream repository at time of review; verify before redistribution.",
                        "preferred_local_path": "tools/bin/longhap",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "Import phased VCF/summary outputs for haplotype-aware ascorbate-pathway interpretation."
                    }
                ],
                "tools_available": 0,
                "tool_count": 1,
                "status": "import_ready",
                "notes": "High value for intergenerational and haplotype-context interpretation."
            },
            {
                "profile_id": "longphase",
                "name": "LongPhase co-phasing profile",
                "category": "phasing",
                "purpose": "Co-phase SNPs, indels, SVs, and 5mC modifications from long reads.",
                "execution_mode": "worker_or_import",
                "import_file_hints": [
                    "longphase",
                    "phase_set",
                    "haplotype block",
                    "5mC"
                ],
                "primary_tools": [
                    {
                        "name": "LongPhase",
                        "purpose": "Co-phase SNPs, small indels, SVs, and 5mC modifications from Nanopore/PacBio long reads.",
                        "license": "GPL-3.0; verify upstream and redistribution requirements.",
                        "preferred_local_path": "tools/bin/longphase",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "Use as optional worker profile for haplotype and modification co-phasing."
                    }
                ],
                "tools_available": 0,
                "tool_count": 1,
                "status": "import_ready",
                "notes": "Useful for broad long-read haplotype context."
            },
            {
                "profile_id": "wf-human-variation",
                "name": "EPI2ME wf-human-variation import profile",
                "category": "ont_reference_workflow",
                "purpose": "Import ONT workflow outputs for small variants, SVs, CNVs, STRs, modified bases, and phasing.",
                "execution_mode": "external_worker_import",
                "import_file_hints": [
                    "wf-human-variation",
                    "epi2me",
                    "nextflow",
                    "small variants",
                    "structural variant",
                    "modified bases"
                ],
                "primary_tools": [
                    {
                        "name": "wf-human-variation",
                        "purpose": "EPI2ME Nextflow workflow for ONT human small variants, SVs, CNVs, STRs, modified bases, and phasing.",
                        "license": "Check Oxford Nanopore/EPI2ME workflow terms and dependencies before redistribution.",
                        "preferred_local_path": "tools/workflows/wf-human-variation",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "Run externally or via worker; ADLA imports derived reports, VCFs, BAM summaries, and bedMethyl outputs."
                    },
                    {
                        "name": "Dorado",
                        "purpose": "ONT basecalling, demultiplexing, alignment support, and modified-base calling from POD5/FAST5 inputs.",
                        "license": "Oxford Nanopore Technologies license; verify redistribution terms before bundling.",
                        "preferred_local_path": "tools/bin/dorado",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "Use from CLI or worker first. GPU/CPU needs may exceed shared hosting constraints. Dorado 2.x includes modified-base workflows and newer small variant capabilities."
                    },
                    {
                        "name": "Modkit",
                        "purpose": "Summarize modified-base BAM/modBAM into bedMethyl and per-region modification reports.",
                        "license": "Check upstream nanoporetech/modkit license before redistribution.",
                        "preferred_local_path": "tools/bin/modkit",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "Primary engine for methylation/modified-base evidence. Output bedMethyl can be parsed by PHP web mode."
                    },
                    {
                        "name": "Sniffles2",
                        "purpose": "Long-read structural variant calling from ONT/PacBio alignments.",
                        "license": "MIT; verify upstream repository.",
                        "preferred_local_path": "tools/bin/sniffles",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "Adds large-deletion/insertion context for pathway and differential diagnosis genes."
                    }
                ],
                "tools_available": 0,
                "tool_count": 4,
                "status": "import_ready",
                "notes": "Too heavy for shared hosting; import reports and derived VCF/bedMethyl outputs."
            },
            {
                "profile_id": "pastforward",
                "name": "PastForward historical/aDNA profile",
                "category": "ancient_dna_workflow",
                "purpose": "Import historical/ancient-DNA mapping, contamination, coverage, and damage-rescaling summaries.",
                "execution_mode": "external_worker_import",
                "import_file_hints": [
                    "pastforward",
                    "damage rescaled",
                    "contamination",
                    "endogenous"
                ],
                "primary_tools": [
                    {
                        "name": "PastForward",
                        "purpose": "Snakemake pipeline for historical/ancient DNA processing, QC, contamination, coverage, and damage rescaling.",
                        "license": "MIT in current upstream repository; verify before redistribution.",
                        "preferred_local_path": "tools/workflows/PastForward",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "ADLA imports PastForward summaries to strengthen ancient/historical readiness."
                    },
                    {
                        "name": "mapDamage2",
                        "purpose": "Ancient DNA nucleotide misincorporation and fragmentation pattern assessment for authenticity/damage review.",
                        "license": "Check upstream license and dependencies before redistribution.",
                        "preferred_local_path": "tools/bin/mapDamage",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "Optional aDNA authentication support. ADLA v0.1.4 records damage/authenticity metadata but does not execute mapDamage in web mode. ADLA v0.1.5 imports summary outputs into the Authentication tab when reports are uploaded."
                    },
                    {
                        "name": "schmutzi",
                        "purpose": "Mitochondrial contamination estimation and endogenous consensus support for ancient human DNA.",
                        "license": "Check upstream license and database terms before redistribution.",
                        "preferred_local_path": "tools/bin/schmutzi",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "Optional contamination/authenticity workflow; output can be summarized in ADLA anthropological context fields. ADLA v0.1.5 imports summary outputs into the Authentication tab when reports are uploaded."
                    }
                ],
                "tools_available": 0,
                "tool_count": 3,
                "status": "import_ready",
                "notes": "Strengthens anthropological readiness and authenticity review."
            },
            {
                "profile_id": "mapache",
                "name": "Mapache aDNA mapping profile",
                "category": "ancient_dna_workflow",
                "purpose": "Import ancient-DNA mapping/QC/imputation workflow summaries.",
                "execution_mode": "external_worker_import",
                "import_file_hints": [
                    "mapache",
                    "snakemake",
                    "mapped reads",
                    "damage rescaling"
                ],
                "primary_tools": [
                    {
                        "name": "Mapache",
                        "purpose": "Snakemake ancient-DNA mapping workflow supporting reproducible mapping/QC/imputation context.",
                        "license": "GPL-3.0; verify redistribution requirements.",
                        "preferred_local_path": "tools/workflows/mapache",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "ADLA imports Mapache summaries and links them to authentication/context fields."
                    },
                    {
                        "name": "mapDamage2",
                        "purpose": "Ancient DNA nucleotide misincorporation and fragmentation pattern assessment for authenticity/damage review.",
                        "license": "Check upstream license and dependencies before redistribution.",
                        "preferred_local_path": "tools/bin/mapDamage",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "Optional aDNA authentication support. ADLA v0.1.4 records damage/authenticity metadata but does not execute mapDamage in web mode. ADLA v0.1.5 imports summary outputs into the Authentication tab when reports are uploaded."
                    }
                ],
                "tools_available": 0,
                "tool_count": 2,
                "status": "import_ready",
                "notes": "Supports reproducible mapping context for older remains."
            },
            {
                "profile_id": "ameta",
                "name": "aMeta ancient metagenomics profile",
                "category": "microbial_context",
                "purpose": "Import ancient microbiome/pathogen/burial-context summaries from aMeta/MALT/KrakenUniq/MaltExtract.",
                "execution_mode": "external_worker_import",
                "import_file_hints": [
                    "ameta",
                    "krakenuniq",
                    "malt",
                    "maltextract",
                    "microbial",
                    "pathogen",
                    "taxa"
                ],
                "primary_tools": [
                    {
                        "name": "aMeta",
                        "purpose": "Ancient metagenomic profiling workflow using trimming/QC, KrakenUniq, Bowtie2 pathogen screening, MapDamage2, MALT, and MaltExtract.",
                        "license": "Check upstream workflow and database terms before redistribution.",
                        "preferred_local_path": "tools/workflows/aMeta",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "ADLA imports aMeta outputs for microbial, pathogen, oral/gut, and burial-context interpretation."
                    },
                    {
                        "name": "KrakenUniq",
                        "purpose": "K-mer-based taxonomic classification used in ancient metagenomic workflows such as aMeta.",
                        "license": "Check upstream license and database terms.",
                        "preferred_local_path": "tools/bin/krakenuniq",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "Contextual microbial/burial evidence only."
                    },
                    {
                        "name": "MALT",
                        "purpose": "MEGAN Alignment Tool for metagenomic alignment/LCA workflows used in ancient microbial authentication.",
                        "license": "Check upstream MEGAN/MALT terms.",
                        "preferred_local_path": "tools/bin/malt-run",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "Use through external aMeta/MALT workflows; import summaries into ADLA."
                    },
                    {
                        "name": "MaltExtract",
                        "purpose": "Authentication and validation of microbial species detected in ancient metagenomic workflows.",
                        "license": "Check upstream license and database terms.",
                        "preferred_local_path": "tools/bin/MaltExtract",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "Import output summaries into ADLA microbial context."
                    },
                    {
                        "name": "mapDamage2",
                        "purpose": "Ancient DNA nucleotide misincorporation and fragmentation pattern assessment for authenticity/damage review.",
                        "license": "Check upstream license and dependencies before redistribution.",
                        "preferred_local_path": "tools/bin/mapDamage",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "Optional aDNA authentication support. ADLA v0.1.4 records damage/authenticity metadata but does not execute mapDamage in web mode. ADLA v0.1.5 imports summary outputs into the Authentication tab when reports are uploaded."
                    }
                ],
                "tools_available": 0,
                "tool_count": 5,
                "status": "import_ready",
                "notes": "Contextual evidence only; useful for preservation, oral/gut/pathogen/burial signals."
            },
            {
                "profile_id": "sv_consensus",
                "name": "Sniffles2/cuteSV structural variant profile",
                "category": "structural_variants",
                "purpose": "Import long-read SV calls and compare target-window overlaps.",
                "execution_mode": "worker_or_import",
                "import_file_hints": [
                    "sniffles",
                    "cutesv",
                    "SVTYPE",
                    "structural variant"
                ],
                "primary_tools": [
                    {
                        "name": "Sniffles2",
                        "purpose": "Long-read structural variant calling from ONT/PacBio alignments.",
                        "license": "MIT; verify upstream repository.",
                        "preferred_local_path": "tools/bin/sniffles",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "Adds large-deletion/insertion context for pathway and differential diagnosis genes."
                    },
                    {
                        "name": "cuteSV",
                        "purpose": "Long-read structural variant caller for ONT/PacBio datasets; useful as an alternate/concordance SV caller with Sniffles2.",
                        "license": "Check upstream license before redistribution.",
                        "preferred_local_path": "tools/bin/cuteSV",
                        "available": false,
                        "web_exec_safe": false,
                        "notes": "Upload cuteSV VCFs to populate ADLA structural-variant target overlaps."
                    }
                ],
                "tools_available": 0,
                "tool_count": 2,
                "status": "import_ready",
                "notes": "Caller concordance is preferred before strong SV interpretation."
            }
        ]
    },
    "external_workflows": {
        "imports": [],
        "summary": {
            "import_count": 0,
            "profiles_observed": [],
            "metric_categories": [],
            "registry_version": "0.1.6",
            "interpretation": "No external workflow outputs were imported."
        },
        "messages": []
    },
    "phasing": {
        "summaries": [],
        "target_haplotype_links": [],
        "summary": {
            "summary_count": 0,
            "reported_phased_variant_count": 0,
            "reported_phase_set_count": 0,
            "target_phased_variant_count": 0,
            "boundary": "Phasing/haplotype evidence supports lineage and allele-context interpretation; it does not make a deficiency call."
        }
    },
    "structural_variants": {
        "target_overlaps": [],
        "summary": {
            "summary_count": 0,
            "reported_sv_count": 0,
            "target_overlap_count": 0,
            "svtype_counts": [],
            "boundary": "SV overlaps are candidate contextual findings. Confirm with read-level inspection and caller concordance."
        }
    },
    "microbial_context": {
        "summaries": [],
        "flagged_taxa": [],
        "summary": {
            "summary_count": 0,
            "flagged_taxa_count": 0,
            "boundary": "Microbial/pathogen/burial context can corroborate preservation, infection, oral/gut environment, or contamination hypotheses; it is not direct ascorbate evidence."
        },
        "boundary": "Microbial and burial-context imports are contextual evidence; they do not establish nutritional deficiency by themselves."
    },
    "tool_status": [
        {
            "name": "Dorado",
            "purpose": "ONT basecalling, demultiplexing, alignment support, and modified-base calling from POD5/FAST5 inputs.",
            "license": "Oxford Nanopore Technologies license; verify redistribution terms before bundling.",
            "preferred_local_path": "tools/bin/dorado",
            "available": false,
            "web_exec_safe": false,
            "notes": "Use from CLI or worker first. GPU/CPU needs may exceed shared hosting constraints. Dorado 2.x includes modified-base workflows and newer small variant capabilities."
        },
        {
            "name": "Modkit",
            "purpose": "Summarize modified-base BAM/modBAM into bedMethyl and per-region modification reports.",
            "license": "Check upstream nanoporetech/modkit license before redistribution.",
            "preferred_local_path": "tools/bin/modkit",
            "available": false,
            "web_exec_safe": false,
            "notes": "Primary engine for methylation/modified-base evidence. Output bedMethyl can be parsed by PHP web mode."
        },
        {
            "name": "NanoPlot",
            "purpose": "Long-read QC plots and HTML summaries for FASTQ/BAM/sequencing_summary inputs.",
            "license": "MIT",
            "preferred_local_path": "tools/bin/NanoPlot",
            "available": false,
            "web_exec_safe": false,
            "notes": "Python dependency stack may be large; can run from CLI worker and cache HTML outputs."
        },
        {
            "name": "chopper",
            "purpose": "Fast ONT read filtering by length, quality, and GC thresholds.",
            "license": "MIT/Apache-style Rust ecosystem dependencies; verify upstream repository.",
            "preferred_local_path": "tools/bin/chopper",
            "available": false,
            "web_exec_safe": false,
            "notes": "Good candidate for vendored binary mode if Hostinger permits executable files."
        },
        {
            "name": "minimap2",
            "purpose": "Long-read alignment to reference genomes.",
            "license": "MIT-like; verify upstream LICENSE.txt.",
            "preferred_local_path": "tools/bin/minimap2",
            "available": false,
            "web_exec_safe": false,
            "notes": "Use -x map-ont for ONT reads. Alignment should generally run in CLI/worker mode."
        },
        {
            "name": "samtools",
            "purpose": "BAM/SAM sorting, indexing, and summary statistics.",
            "license": "MIT/BSD-style; verify htslib/samtools license.",
            "preferred_local_path": "tools/bin/samtools",
            "available": false,
            "web_exec_safe": false,
            "notes": "Core dependency for BAM preparation."
        },
        {
            "name": "mosdepth",
            "purpose": "Fast BAM/CRAM depth summaries and target coverage/callability checks.",
            "license": "MIT; verify upstream repository.",
            "preferred_local_path": "tools/bin/mosdepth",
            "available": false,
            "web_exec_safe": false,
            "notes": "Important for proving whether target genes/windows were callable."
        },
        {
            "name": "Clair3",
            "purpose": "Long-read germline small variant calling, including ONT models.",
            "license": "Check upstream HKU-BAL/Clair3 license and model terms.",
            "preferred_local_path": "tools/bin/run_clair3.sh",
            "available": false,
            "web_exec_safe": false,
            "notes": "Use as worker/CLI stage. Outputs VCF that web mode can parse."
        },
        {
            "name": "Sniffles2",
            "purpose": "Long-read structural variant calling from ONT/PacBio alignments.",
            "license": "MIT; verify upstream repository.",
            "preferred_local_path": "tools/bin/sniffles",
            "available": false,
            "web_exec_safe": false,
            "notes": "Adds large-deletion/insertion context for pathway and differential diagnosis genes."
        },
        {
            "name": "Ensembl VEP",
            "purpose": "Offline/cache-based variant consequence annotation with transcript/protein effects, consequence terms, frequencies, and plugin support.",
            "license": "Apache 2.0 for Ensembl API code; data cache terms vary. Verify before redistribution.",
            "preferred_local_path": "tools/bin/vep",
            "available": false,
            "web_exec_safe": false,
            "notes": "Use --offline --cache --assembly GRCh38 with a local cache under tools/annotations/vep_cache. ADLA parses VEP CSQ fields from annotated VCFs."
        },
        {
            "name": "bcftools",
            "purpose": "Local VCF normalization, target slicing, indexing-aware filtering, and annotation transfer from ClinVar/dbSNP VCFs.",
            "license": "MIT/BSD-style htslib/samtools family; verify upstream version.",
            "preferred_local_path": "tools/bin/bcftools",
            "available": false,
            "web_exec_safe": false,
            "notes": "Primary lightweight engine for offline ClinVar/dbSNP annotation and ADLA target-slice generation."
        },
        {
            "name": "tabix",
            "purpose": "Index bgzip-compressed VCF/BED annotation files for local random access.",
            "license": "MIT/BSD-style htslib/samtools family; verify upstream version.",
            "preferred_local_path": "tools/bin/tabix",
            "available": false,
            "web_exec_safe": false,
            "notes": "Required for indexed ClinVar/dbSNP VCF usage."
        },
        {
            "name": "bgzip",
            "purpose": "Block gzip compression for VCF/BED files that need tabix indexing.",
            "license": "MIT/BSD-style htslib/samtools family; verify upstream version.",
            "preferred_local_path": "tools/bin/bgzip",
            "available": false,
            "web_exec_safe": false,
            "notes": "Used by annotation prep scripts when normalizing or slicing local reference VCFs."
        },
        {
            "name": "SnpEff",
            "purpose": "Alternative local variant effect annotation when VEP cache is not installed.",
            "license": "Verify current SnpEff license before redistributing jar files.",
            "preferred_local_path": "tools/bin/snpEff.jar",
            "available": false,
            "web_exec_safe": false,
            "notes": "Java runtime required. Use as optional alternative to VEP, not as the primary ADLA consequence engine."
        },
        {
            "name": "SnpSift",
            "purpose": "Annotate/filter VCFs using local ClinVar, dbSNP, dbNSFP, and other indexed files.",
            "license": "Verify current SnpSift/SnpEff license before redistributing jar files.",
            "preferred_local_path": "tools/bin/SnpSift.jar",
            "available": false,
            "web_exec_safe": false,
            "notes": "Useful fallback for ClinVar/dbSNP enrichment and field extraction."
        },
        {
            "name": "clinvcf",
            "purpose": "Optional ClinVar XML-to-enhanced-VCF builder supporting GRCh37/GRCh38; useful if raw ClinVar VCF is insufficient for local interpretation workflows.",
            "license": "Check upstream SeqOne/clinvcf license before redistribution.",
            "preferred_local_path": "tools/bin/clinvcf",
            "available": false,
            "web_exec_safe": false,
            "notes": "Optional advanced curation path. ADLA can operate from official ClinVar VCF without this tool."
        },
        {
            "name": "mapDamage2",
            "purpose": "Ancient DNA nucleotide misincorporation and fragmentation pattern assessment for authenticity/damage review.",
            "license": "Check upstream license and dependencies before redistribution.",
            "preferred_local_path": "tools/bin/mapDamage",
            "available": false,
            "web_exec_safe": false,
            "notes": "Optional aDNA authentication support. ADLA v0.1.4 records damage/authenticity metadata but does not execute mapDamage in web mode. ADLA v0.1.5 imports summary outputs into the Authentication tab when reports are uploaded."
        },
        {
            "name": "PMDtools",
            "purpose": "Post-mortem damage score support for ancient DNA read filtering/authenticity workflows.",
            "license": "Check upstream license before redistribution.",
            "preferred_local_path": "tools/bin/pmdtools",
            "available": false,
            "web_exec_safe": false,
            "notes": "Optional ancient/historical sample readiness component for CLI/worker mode. ADLA v0.1.5 imports summary outputs into the Authentication tab when reports are uploaded."
        },
        {
            "name": "schmutzi",
            "purpose": "Mitochondrial contamination estimation and endogenous consensus support for ancient human DNA.",
            "license": "Check upstream license and database terms before redistribution.",
            "preferred_local_path": "tools/bin/schmutzi",
            "available": false,
            "web_exec_safe": false,
            "notes": "Optional contamination/authenticity workflow; output can be summarized in ADLA anthropological context fields. ADLA v0.1.5 imports summary outputs into the Authentication tab when reports are uploaded."
        },
        {
            "name": "ContamLD",
            "purpose": "Autosomal ancient-DNA contamination estimation using linkage disequilibrium breakdown; useful as an advanced nuclear-contamination context layer.",
            "license": "Check upstream Reich Lab/ContamLD terms before redistribution.",
            "preferred_local_path": "tools/bin/contamLD",
            "available": false,
            "web_exec_safe": false,
            "notes": "Optional future CLI/worker tool. ADLA v0.1.5 can import contamination summary outputs when provided as text/JSON."
        },
        {
            "name": "ANGSD",
            "purpose": "Genotype-likelihood framework used in low-coverage and ancient DNA contexts, including chromosome-X contamination estimation workflows for applicable samples.",
            "license": "Check upstream ANGSD license before redistribution.",
            "preferred_local_path": "tools/bin/angsd",
            "available": false,
            "web_exec_safe": false,
            "notes": "Optional future CLI/worker tool. Requires careful setup, population frequency sites, and sex/chromosome applicability review."
        },
        {
            "name": "hapCon",
            "purpose": "Ancient DNA contamination estimation for male X-chromosome workflows; useful where applicable and when reference panels/metadata are appropriate.",
            "license": "Check upstream terms and reference-data requirements before redistribution.",
            "preferred_local_path": "tools/bin/hapCon",
            "available": false,
            "web_exec_safe": false,
            "notes": "Optional future CLI/worker tool. ADLA can import summary metrics but does not execute it in web mode."
        },
        {
            "name": "fastVEP",
            "purpose": "High-performance Rust variant consequence annotation with VEP-compatible outputs and supplementary database integration.",
            "license": "Check upstream fastVEP license and bundled database terms before redistribution.",
            "preferred_local_path": "tools/bin/fastvep",
            "available": false,
            "web_exec_safe": false,
            "notes": "ADLA parses fastVEP JSON/VCF-style imports and can use it as a worker annotation profile."
        },
        {
            "name": "LongHap",
            "purpose": "Read-based phasing that integrates native long-read methylation signals with variant calls.",
            "license": "MIT per upstream repository at time of review; verify before redistribution.",
            "preferred_local_path": "tools/bin/longhap",
            "available": false,
            "web_exec_safe": false,
            "notes": "Import phased VCF/summary outputs for haplotype-aware ascorbate-pathway interpretation."
        },
        {
            "name": "LongPhase",
            "purpose": "Co-phase SNPs, small indels, SVs, and 5mC modifications from Nanopore/PacBio long reads.",
            "license": "GPL-3.0; verify upstream and redistribution requirements.",
            "preferred_local_path": "tools/bin/longphase",
            "available": false,
            "web_exec_safe": false,
            "notes": "Use as optional worker profile for haplotype and modification co-phasing."
        },
        {
            "name": "wf-human-variation",
            "purpose": "EPI2ME Nextflow workflow for ONT human small variants, SVs, CNVs, STRs, modified bases, and phasing.",
            "license": "Check Oxford Nanopore/EPI2ME workflow terms and dependencies before redistribution.",
            "preferred_local_path": "tools/workflows/wf-human-variation",
            "available": false,
            "web_exec_safe": false,
            "notes": "Run externally or via worker; ADLA imports derived reports, VCFs, BAM summaries, and bedMethyl outputs."
        },
        {
            "name": "PastForward",
            "purpose": "Snakemake pipeline for historical/ancient DNA processing, QC, contamination, coverage, and damage rescaling.",
            "license": "MIT in current upstream repository; verify before redistribution.",
            "preferred_local_path": "tools/workflows/PastForward",
            "available": false,
            "web_exec_safe": false,
            "notes": "ADLA imports PastForward summaries to strengthen ancient/historical readiness."
        },
        {
            "name": "Mapache",
            "purpose": "Snakemake ancient-DNA mapping workflow supporting reproducible mapping/QC/imputation context.",
            "license": "GPL-3.0; verify redistribution requirements.",
            "preferred_local_path": "tools/workflows/mapache",
            "available": false,
            "web_exec_safe": false,
            "notes": "ADLA imports Mapache summaries and links them to authentication/context fields."
        },
        {
            "name": "aMeta",
            "purpose": "Ancient metagenomic profiling workflow using trimming/QC, KrakenUniq, Bowtie2 pathogen screening, MapDamage2, MALT, and MaltExtract.",
            "license": "Check upstream workflow and database terms before redistribution.",
            "preferred_local_path": "tools/workflows/aMeta",
            "available": false,
            "web_exec_safe": false,
            "notes": "ADLA imports aMeta outputs for microbial, pathogen, oral/gut, and burial-context interpretation."
        },
        {
            "name": "cuteSV",
            "purpose": "Long-read structural variant caller for ONT/PacBio datasets; useful as an alternate/concordance SV caller with Sniffles2.",
            "license": "Check upstream license before redistribution.",
            "preferred_local_path": "tools/bin/cuteSV",
            "available": false,
            "web_exec_safe": false,
            "notes": "Upload cuteSV VCFs to populate ADLA structural-variant target overlaps."
        },
        {
            "name": "KrakenUniq",
            "purpose": "K-mer-based taxonomic classification used in ancient metagenomic workflows such as aMeta.",
            "license": "Check upstream license and database terms.",
            "preferred_local_path": "tools/bin/krakenuniq",
            "available": false,
            "web_exec_safe": false,
            "notes": "Contextual microbial/burial evidence only."
        },
        {
            "name": "MALT",
            "purpose": "MEGAN Alignment Tool for metagenomic alignment/LCA workflows used in ancient microbial authentication.",
            "license": "Check upstream MEGAN/MALT terms.",
            "preferred_local_path": "tools/bin/malt-run",
            "available": false,
            "web_exec_safe": false,
            "notes": "Use through external aMeta/MALT workflows; import summaries into ADLA."
        },
        {
            "name": "MaltExtract",
            "purpose": "Authentication and validation of microbial species detected in ancient metagenomic workflows.",
            "license": "Check upstream license and database terms.",
            "preferred_local_path": "tools/bin/MaltExtract",
            "available": false,
            "web_exec_safe": false,
            "notes": "Import output summaries into ADLA microbial context."
        }
    ],
    "interpretation": {
        "overall_confidence": "insufficient_for_deficiency_call",
        "messages": [
            {
                "class": "anthropological_boundary",
                "level": "required",
                "message": "Sequencing cannot directly measure vitamin C status. In ADLA, genomic and epigenomic findings are anthropological research signals that require archaeological, osteological, isotopic, ecological, historical, and preservation context before interpretation."
            },
            {
                "class": "anthropological_context",
                "level": "context",
                "message": "Anthropological context mode: modern or unknown research context; corroboration score 0/100."
            },
            {
                "class": "genetic_transport",
                "level": "neutral",
                "message": "No curated ascorbate-transporter rsID hits were detected in parsed VCF inputs. This is not proof of absence unless target regions were callable."
            },
            {
                "class": "target_callability",
                "level": "not_available",
                "message": "No mosdepth/coverage target report was parsed. Variant absence and methylation absence should be treated as unknown until target callability is measured."
            },
            {
                "class": "modified_base",
                "level": "not_available",
                "message": "No target-region modified-base summaries were available. Upload Modkit bedMethyl or run modkit from modBAM through the CLI pipeline."
            }
        ],
        "recommended_next_steps": [
            "Confirm sample type, reference build, and target-region coverage/callability using the generated BED panel.",
            "Pair sequencing output with osteological/paleopathological, isotopic, ecological, and historical dietary evidence; use biochemical ascorbate only when modern/historical sample context makes it available.",
            "Run the offline annotation stage with VEP cache, ClinVar VCF, dbSNP VCF, and/or SnpSift/bcftools before interpreting unclassified target-region variants.",
            "Review the ADLA priority score only as a triage/ranking aid; inspect the evidence components and source dates for every high-scoring hit.",
            "Use matched controls and method-specific ancient/modern methylation workflows before interpreting methylation directionality.",
            "When available, import fastVEP/VEP, LongHap/LongPhase, Sniffles2/cuteSV, wf-human-variation, PastForward/Mapache, and aMeta outputs so ADLA can connect annotation, phasing, SVs, authentication, and microbial context."
        ],
        "scientific_boundary": "ADLA evaluates genomic, modified-base, preservation, and contextual evidence relevant to ascorbate stress and scurvy-like vulnerability in anthropological, historical, ancient-remains, and intergenerational research. It does not diagnose vitamin C deficiency or scurvy."
    },
    "notes": [
        {
            "level": "info",
            "message": "JSON file detected. Name authentication reports with mapDamage/schmutzi/PMDtools/authentication/authenticity in the filename so ADLA imports structured ancient-DNA metrics.",
            "at": "2026-07-07T06:57:00+00:00"
        }
    ]
}