Liquid-Biopsy Capability Matrix¶
This page is the single overview of the current user-facing Liquid Agent capability surface. It maps callable models, tools, methods, and workflow blocks to the liquid-biopsy data types they handle.
Status Semantics¶
| Status | Meaning |
|---|---|
| Internal executable | Liquid Agent can run this through the Python kernel, scripts, shell, Web API, or autopilot when required inputs exist. |
| Internal model / encoder | The model or deterministic encoder is registered in the blood-signal encoding layer. |
| External runtime wrapper | Liquid Agent can check, install/prepare where possible, smoke-test, and call the runtime through liquid-agent tools. Real analysis may still need model files, references, manifests, or compatible input files. |
| External method guidance | The method advisor can recommend it, show requirements, and choose internal fallbacks, but no stable local wrapper is registered yet. |
| Reimplementation candidate | The original method is useful but the public runtime is too old or unstable for ordinary users; prefer a future small internal proxy or a maintained alternative. |
| LLM engine | Used for conversation, planning support, documentation context, result explanation, and recovery suggestions. It is not a biomedical signal model. |
Recently Added Kernel Features¶
| Feature | Status | Data or question type | User-facing entrypoints |
|---|---|---|---|
| Frozen prediction studies | Internal executable | Explicit binary train/validation contracts; logistic, SVM and forest candidates; training-only preprocessing and threshold selection; ROC/PR/calibration and frozen probabilities | Natural-language Web/CLI tools; see prediction studies. Not a separate Plan-button entry or automatic clinical cohort design. |
| Paired prediction comparisons | Internal executable | Two to six completed feature-set studies with matching cohorts and unchanged inputs/probabilities; paired AUROC differences without parent refitting | Natural-language Web/CLI tools and owned Results reports; exploratory intervals, not multiplicity-adjusted or clinical validation |
| Liquid-biopsy method advisor registry | Internal executable | Method/tool questions across fragmentomics, methylation, copy-number, variants, cfRNA, small RNA, CTC tables, and proteomics | /methods, liquid-agent methods, scripts/run_liquid_biopsy_method_advisor.py, Web Method advice button, Python API |
| Named-tool ranking | Internal executable | Questions that explicitly name tools such as cfDNAPro, WisecondorX, FinaleMe, or cfTools | Natural language, /methods, CLI, Web API |
| Dependency and manual-resource status | Internal executable | External methods that require executables, R packages, Python modules, Java, reference panels, model files, or code bundles | Method-advice JSON/Markdown reports |
| External runtime manager | Internal executable | Selected non-kernel Python, R/Bioconductor, source, Snakemake, and system-binary tools | liquid-agent tools status/install/smoke/run, external-tool status reports |
| Supplied signal-matrix analysis | Internal executable | Processed CNV, methylation, EPIC-like methylated/unmethylated, or other liquid-biopsy numeric matrices | scripts/run_cfdna_analysis_suite.py, scripts/run_cfdna_plot_suite.py, /plan, /autopilot, Web results |
| Metadata profile scanner | Internal executable | CSV, TSV, Excel, Parquet, JSON, JSONL, and NDJSON metadata or label tables | /metadata, Web Metadata card, Web scan/plan responses, planner inputs |
| Label-aware planning | Internal executable | Datasets with candidate sample labels, groups, response/status columns, or user-selected labels | /plan, /metadata use, Web Change/Ignore controls; chooses unsupervised, grouped, or exploratory supervised mode |
| Exploratory supervised modeling | Internal executable when backend is available | Labeled feature stores, embeddings, or processed signal matrices with adequate matched labels | Standard cfDNA analysis task; sklearn_logistic_regression by default, optional pytorch_linear_probe for larger labeled cohorts |
| Markdown-first result reports | Internal executable | Completed runs, generated tables, static figures, method-advice reports, and result evaluations | Web Results panel, liquid-agent results, autopilot reports; hides backend JSON/TXT/HTML clutter from the default user view |
| Agent planning integration | Internal executable | Dataset folders with blood raw candidates, fragmentomics outputs, CNV inputs, coverage tracks, variant inputs, region-signal tables, or browser-track style inputs | /plan, /autopilot, Web scan/plan |
| LiquidBiopsyDataState summary | Internal executable | Any scanned liquid-biopsy source or generated result set | Backend planner, result evaluator, plan ledger, autopilot report; records signal families, input/output counts, metadata coverage, minimum-output contract gaps, blockers, and safe next actions without adding user-facing controls |
| Liquid-biopsy FeatureBook contracts | Internal executable | Fragmentomics, methylation, copy-number, variant, supplied matrix, archive, and metadata/grouped-comparison contexts | Planner, result evaluator, plan ledger, autopilot report, Python API; tracks expected artifacts, QC checks, interpretation limits, and satisfied/pending contract status |
| ToolCard output-kind verification | Internal executable | Completed backend tasks and external-wrapper task summaries | Executor, plan ledger, autopilot report; verifies minimum output kinds such as summary, table, figure, method-advice report, review, or feature store; a bare output directory is not treated as completion, but real result files inside a reported output/run directory are sampled and counted |
| Content-derived result signals | Internal executable | Ranked effect tables, grouped summaries, label-metric summaries, sample outlier tables, and summary JSONs from liquid-biopsy runs | Result evaluator, planner notes, plan ledger, autopilot report; can promote ready visualization, raw-signal follow-up, signal-aware method advice, or review tasks without adding user-facing controls |
| Result-driven analysis concepts | Internal executable | Content-derived liquid-biopsy result signals plus FeatureBook contracts | Result evaluator, planner notes, plan ledger, autopilot report; converts real evidence into prioritized auditable follow-up questions, suggested task families, QC checks, interpretation limits, and stable novelty keys without adding user-facing controls |
| Method-advice internal fallback routing | Internal executable | Method-advice JSON with top methods, resource limits, and internal fallback routes | Planner and plan ledger; can map fallback evidence back to ready standard cfDNA analysis, standard visualization, raw-signal analysis, or raw-signal visualization without adding user-facing controls |
| Source-aware Web method advice | Internal executable | Single-source or multi-source Web sessions | POST /api/session/{session_id}/methods/advice |
| Planner robustness for incomplete candidates | Internal executable | Folders with incomplete candidate files where encoding cannot be safely planned yet | Planning continues with feasible tasks and records a note instead of crashing |
| Documentation and prompt examples for method advice | Documentation | Natural-language examples and reproducible command forms | README, docs site, script cookbook |
Direct Internal Workflow Blocks¶
Explicit Assay Contracts¶
These operations use a validated *.assay.json declaration or the controller's
configure_assay tool. They are not inferred from a filename or started by loading
a skill. See schemas and limits.
| Operation | Implemented engine | Boundary |
|---|---|---|
| Digital-PCR accepted partitions | Occupancy concentration and transformed exact-binomial 95% intervals | No raw droplet gating, duplex fitting or clinical detection threshold |
| CTC accepted counts/volume | Cells per mL and exact Poisson 95% intervals | No image-based identity assignment or enrichment correction |
| RNA, protein, metabolite and EV processed matrices | Missingness, distributions, sample/feature QC, bounded PCA and heatmaps | Not raw instrument identification or biological source validation |
| Methylation beta matrices | Range validation, missingness and sample/probe displays | Not IDAT normalization, conversion QC or DMR fitting |
| Independent-group RNA raw counts | PyDESeq2, Wald tests and adjusted p-values | Explicit separate request; no paired/batch/time design; experimental replication required |
Every completed operation produces a Markdown report, actual PNG/CSV outputs and provenance. Optional dependencies are checked when used.
Existing Workflow Blocks¶
| Workflow block | Status | Main data types | Main entrypoints | Typical outputs |
|---|---|---|---|---|
| Dataset/source scanning | Internal executable | Folders, files, multiple attached liquid-biopsy sources | /use, /sources, Web source manager, scan_project_profile(...) |
Detected signal candidates, labels, outputs, source inventory |
| Blood-signal preprocessing | Internal executable | BED/BED.GZ, peak files, BAM/CRAM, VCF/MAF, CSV/TSV/parquet variant tables | /preprocess-style natural language, autopilot, scripts/preprocess_*_signal.py, Python API |
Cleaned intervals, region-signal tables, bin counts, segments, arm burden, normalized variant tables, summaries |
| Blood-signal encoding | Internal executable | cfChIP/cfMeDIP/MeDIP intervals or alignments, LPWGS/ULPWGS intervals or CNV tables, VCF/MAF variant tables, continuous tracks | /blood, natural language, scripts/encode_*_features.py, Python API |
Feature stores, encoder summaries, reusable per-sample vectors |
| Standard cfDNA analysis | Internal executable | Feature stores, fragmentomics summaries, methylation-proxy tables, CNV directories, region-signal tables, supplied CNV/methylation/signal matrices, labels | scripts/run_cfdna_analysis_suite.py, autopilot, Python API |
Distance/correlation/outlier summaries, grouped metrics, supplied-matrix summaries, module summaries |
| Standard cfDNA visualization | Internal executable | Feature stores, metadata/labels, fragmentomics summaries, methylation-proxy tables, CNV directories, supplied CNV/methylation/signal matrices | scripts/run_cfdna_plot_suite.py, autopilot, Python API |
UMAP/t-SNE/PCA scatter, heatmaps, grouped plots, supplied-matrix PNG outputs, static figures for markdown reports, optional Plotly HTML files from Python |
| Raw-signal visualization | Internal executable | Fragment directories, CNV/bin directories, coverage tracks, region-signal tables, variant inputs, end-motif tables, loci tables | scripts/run_cfdna_raw_signal_suite.py, autopilot, Python API |
Fragment-length plots, genomewide profiles, sample/bin heatmaps, region metaprofiles, VAF plots, motif plots, browser-track inventories, optional Plotly HTML files from Python |
| Raw-signal numeric analysis | Internal executable | Fragment directories, CNV/bin directories, coverage tracks, region-signal tables, variant inputs, end-motif tables, sample-time tables, browser-track files | scripts/run_cfdna_raw_signal_analysis_suite.py, autopilot, Python API |
Fragmentomics metrics, CNV summaries, arm burden, VAF summaries, longitudinal summaries, browser-track summaries, numeric report JSON |
| Method/tool advice | Internal executable | Dataset folders and natural-language method questions | /methods, CLI, Web API, Python API |
liquid_biopsy_method_advice.json, liquid_biopsy_method_advice.md |
| Result review and report summary | Internal executable | Existing Liquid Agent outputs and reports | /review, autopilot final pass, Python API |
Consolidated review JSON/TXT, next actions |
| Closed-loop agent ledger and result evaluation | Internal executable | Dataset scans, generated summaries, content-derived result signals, result-driven analysis concepts, pending/actioned/blocked concept lifecycle records, method-advice content, tables, figures, reports, failures, and run records | /plan, /autopilot, Web plan/run/results, PlanLedger, PlanLedger.concept_memory(), PlanLedger.write_concept_book(), evaluate_project_results(...) |
assistant/ledger/plan_*.json, run_*.json, result_evaluation_*.json, analysis_concept_book.json, planner evidence notes, plan-level concept-memory snapshots and deltas, concept verification and blocker status, concept-memory-grounded next actions, audit-style autopilot reports |
| FeatureBook-based signal verification | Internal executable | Common liquid-biopsy signal families and generated artifacts | Internal planner/evaluator, list_feature_specs(...), compile_user_analysis_idea(...) |
Feature contracts, compiled user idea, plan novelty evidence, report-level satisfied/pending status |
| Professional skill memory and workflow contracts | Internal executable | Markdown, text, PDFs where supported by runtime, URLs, directories, expert notes, workflow.yaml playbooks |
/skills, /skills explain-plan, Web skills endpoints, Python API |
Skill documents, skill cache, workflow triggers, required outputs, quality checks, context snippets for future planning |
Preprocessing Profiles¶
| Signal family | Supported inputs | Default profile | Other callable profiles | Main data products |
|---|---|---|---|---|
cfchip_seq |
BED/BED.GZ, narrowPeak/broadPeak/gappedPeak, BAM/CRAM | cfchip_interval_cleanup |
cfchip_panel_summary, cfchip_background_aware |
Cleaned intervals, optional region-panel summaries, optional background-normalized summaries |
cfmedip_seq |
BED/BED.GZ, narrowPeak/broadPeak/gappedPeak, BAM/CRAM | cfmedip_interval_cleanup |
cfmedip_panel_summary, cfmedip_scale_normalized_panel |
Cleaned intervals, methylation-panel summaries, optional scale-normalized summaries |
medip_seq |
BED/BED.GZ, narrowPeak/broadPeak/gappedPeak, BAM/CRAM | medip_interval_cleanup |
medip_panel_summary, medip_scale_normalized_panel |
Same route as cfMeDIP-style methylation enrichment |
lpwgs |
BED/BED.GZ, BAM/CRAM | lpwgs_interval_cleanup |
lpwgs_cleanup_only, lpwgs_gc_corrected |
Cleaned intervals, genome bins, corrected bins when annotations exist, segments, arm burden |
ulpwgs |
BED/BED.GZ, BAM/CRAM | ulpwgs_interval_cleanup |
ulpwgs_cleanup_only, ulpwgs_gc_corrected |
Same route as LPWGS, tuned for ultra-low-pass data |
ctdna_variant |
VCF/VCF.GZ, MAF/MAF.GZ, MAF TSV, CSV/TSV/parquet tables | variant_table_qc |
variant_strict_somatic, variant_matched_normal |
Normalized variant tables, conservative filters, matched-normal overlap filtering when supplied |
variant |
VCF/VCF.GZ, MAF/MAF.GZ, MAF TSV, CSV/TSV/parquet tables | variant_table_qc |
variant_strict_somatic, variant_matched_normal |
Same route as ctDNA variant preprocessing |
Internal Encoders And Models¶
| Signal family | Data types | Default encoder/model | Optional encoders/models | Status |
|---|---|---|---|---|
cfchip_seq |
BED/BED.GZ, peak files, BAM/CRAM, bedGraph/WIG/bigWig | ntv2 |
dnabert2, hyenadna, caduceus, epibert, epcot, enformer, coverage_profile |
Internal model / encoder |
cfmedip_seq |
BED/BED.GZ, peak files, BAM/CRAM, bedGraph/WIG/bigWig | epibert |
ntv2, dnabert2, hyenadna, caduceus, epcot, enformer, coverage_profile |
Internal model / encoder |
medip_seq |
BED/BED.GZ, peak files, BAM/CRAM, bedGraph/WIG/bigWig | epibert |
ntv2, dnabert2, hyenadna, caduceus, epcot, enformer, coverage_profile |
Internal model / encoder |
lpwgs |
BED/BED.GZ, BAM/CRAM, cnv_parquet, bedGraph/WIG/bigWig |
lpwgs_cnv_profile |
coverage_profile, ntv2, dnabert2, hyenadna, caduceus, epibert, epcot, enformer |
Internal model / encoder |
ulpwgs |
BED/BED.GZ, BAM/CRAM, cnv_parquet, bedGraph/WIG/bigWig |
lpwgs_cnv_profile |
coverage_profile, DNA foundation encoders listed above |
Internal model / encoder |
ctdna_variant |
VCF/VCF.GZ, MAF/MAF.GZ, MAF TSV | vcf_signature |
variant_effect_profile when CADD, SpliceAI, DeepSEA, or similar effect scores exist |
Internal model / encoder |
variant |
VCF/VCF.GZ, MAF/MAF.GZ, MAF TSV | vcf_signature |
variant_effect_profile |
Internal model / encoder |
External Method Advisor Registry¶
| Method/tool | Status | Primary data types | Best used for |
|---|---|---|---|
| FinaleToolkit | External runtime wrapper | Paired-end cfDNA WGS BAM/CRAM or indexed fragment files | Fragment length, coverage, WPS, DELFI-style features, end motifs, cleavage profiles |
| DELFI-style features | Advisory/internal proxy | Low-pass paired-end cfDNA WGS fragments | Genomewide fragmentome features and cancer-monitoring style feature matrices |
| cfDNAPro | Advisory external | Paired-end cfDNA WGS BAM in R/Bioconductor workflows | Robust fragment curation, fragment-length metrics, motif-oriented summaries |
| Griffin | Advisory external | cfDNA WGS around predefined loci | Nucleosome profiling, tissue-of-origin and accessibility-style follow-up |
| LIQUORICE | Advisory external | cfDNA WGS BAM plus BED regions | Bias-corrected region-centered coverage changes |
| LBFextract | Advisory external | cfDNA WGS BAM plus region/BED sets | Regulatory-region fragmentomics and coverage/fragment-length feature extraction |
| cfDNApipe | Advisory external | cfDNA WGS/WGBS FASTQ or BAM | Broad external WGS/WGBS QC, CNV, DMR, and fragment-size workflows |
| cfDNA UniFlow | External runtime wrapper | cfDNA WGS FASTQ/BAM plus workflow configuration | Standardized WGS preprocessing, QC, GC-bias correction, copy-number state estimation, and region signal extraction |
| cfDNAFE | External runtime wrapper | cfDNA WGS/WGBS intermediate files or fragment files | Multi-signal feature extraction across fragmentation, WPS, OCF, CNV, and methylation-derived features |
| cfDNAanalyzer | External method guidance | cfDNA sequencing BAM manifests | CNA, end-motif, footprinting, nucleosome, WPS, OCF, and promoter-fragmentation-entropy feature matrices |
| EMIT | External runtime wrapper / research | cfDNA end-motif tables | Transformer-based end-motif representation learning and linear-probe cancer-detection experiments |
| DeepFRAG | External runtime wrapper / watchlist | cfDNA fragment-size distributions with labels | Deep fragment-size probability modeling for supervised cancer-detection experiments |
| ichorCNA | Advisory external | ULP-WGS/LPWGS cfDNA WIG/read-count bins | Tumor fraction and broad copy-number alteration inference |
| QDNAseq | Advisory external | Shallow WGS / LPWGS BAM files | Binning, correction, segmentation, and copy-number calling |
| WisecondorX | Advisory external | Shallow WGS / cfDNA low-pass WGS BAM/CRAM | Reference-based shallow-WGS CNV detection |
| HMMcopy | Advisory external | Windowed WGS readcounts with GC/mappability tracks | Readcount correction before CNV workflows |
| CNVkit | External runtime wrapper | Targeted DNA, WES, WGS BAM files | Read-depth CNV detection and visualization |
| Control-FREEC | Advisory external | WGS/WES/targeted read depth plus BAF | Copy-number and LOH calling in higher-coverage designs |
| CopywriteR | Reimplementation candidate / legacy with internal copywriter-proxy |
Targeted or exome off-target reads, interval/bin-count tables | First-pass off-target/bin-count CNV screening when the original archived R/Bioconductor stack is not suitable |
| FACETS / facetsSuite | External runtime wrapper, core FACETS installed separately from pileup resources | Paired tumor-normal WGS/WES/targeted SNP pileups | Allele-specific copy number, purity, ploidy, and LOH |
| PureCN | External runtime wrapper | Targeted short-read DNA or WES BAM/coverage plus optional VCF | Targeted-panel copy number, purity/ploidy, LOH, and SNV classification support |
| BayesCNV | External runtime wrapper / watchlist | Targeted cfDNA panel coverage/features | Bayesian somatic amplification detection in low-tumor-content targeted cfDNA settings |
| QSEA | Advisory external | MeDIP/cfMeDIP enrichment BAM and windows | Methylation-enrichment modeling using CpG density and calibration assumptions |
| MEDIPS | Advisory external | MeDIP/cfMeDIP BAM and reference CpG annotations | Methylation-enrichment QC, saturation, CpG coverage, enrichment summaries |
| Bismark | Advisory external | WGBS/RRBS/bisulfite FASTQ | Bisulfite alignment and methylation calling |
| MethylDackel | Advisory external | Aligned bisulfite/EM-seq BAM/CRAM | CpG methylation extraction from alignments |
| nf-core/methylseq | Advisory external | Bisulfite/EM-seq FASTQ samplesheets | Production-style FASTQ-to-report methylation workflow |
| FinaleMe | Advisory external | cfDNA WGS fragmentation-derived features plus FinaleMe resources | Exploratory methylation prediction from cfDNA fragmentation |
| cfTools / cfSort | Advisory external | WGBS/cfMethyl-Seq methylation calls and marker references | Tissue-of-origin, tumor-burden, CancerDetector, cfDeconvolve, cfSort analyses |
| MethylBERT | External runtime wrapper / research | Read-level WGBS or Dorado-called methylation patterns | Transformer-based read classification and methylation deconvolution |
| cfDecon | External runtime wrapper / research source checkout | cfDNA methylation reads or method-specific feature tables | Deep autoencoder-based cell-type deconvolution |
| CelFiE-ISH | External method guidance / research | Single-molecule/read-haplotype methylation data | Haplotype-aware multi-cell-type deconvolution and rare-cell-type detection |
| CelFEER | External runtime wrapper / research source checkout | Read-level cfDNA WGBS methylation | Benchmark-supported read-level methylation deconvolution |
| UXM | External runtime wrapper with binary/resource gaps | Fragment-level methylation states plus atlas resources | Unmethylated-fragment deconvolution of cfDNA tissue fractions |
| MethAtlas | External runtime wrapper / research source checkout | Methylation ratio matrices plus atlas resources | Fast interpretable atlas-based tissue deconvolution |
| cfNOMe | External runtime wrapper / research source checkout | NOMe/cfNOMe-compatible methylation outputs | Tissue-of-origin deconvolution plus nucleosome occupancy summaries |
| MetDecode | External runtime wrapper / research | Marker-region methylated/total CpG counts | Methylation-based cfDNA deconvolution for multi-cancer typing |
| CpGPT / MethylGPT / MethFormer | Mixed: CpGPT/MethylGPT runtime wrappers; MethFormer model-resource guidance | Methylation matrices or regional methylation tensors | Foundation-model embeddings, imputation, and transfer-learning experiments |
| cfMethylPre | Advisory literature watchlist | cfDNA methylation profiles plus sequence embeddings | Transfer-learning cancer-detection model concept |
| Dorado + modkit | External runtime wrapper for modkit; Dorado remains explicit system/model resource | Nanopore cfDNA POD5/FAST5 or modified-base BAM | Modified-base calling and methylation coordinate extraction |
| fgbio | Advisory external | UMI-tagged targeted sequencing BAM/FASTQ | UMI consensus preprocessing before low-VAF variant calling |
| Mutect2 / LoFreq / VarDict | Advisory external | Targeted, WES, or cfDNA BAM/CRAM | Low-VAF ctDNA SNV/indel calling |
| Salmon / STAR / featureCounts | Advisory external | cfRNA FASTQ or count matrices | cfRNA quantification and expression matrix generation |
| sRNAbench / miRge-style routes | Advisory external | Small-RNA FASTQ or miRNA count matrices | EV-miRNA or plasma small-RNA profiling |
| Scanpy / Seurat / CellTypist-style downstream routes | Advisory external | CTC count tables, marker matrices, h5ad/RDS-style outputs | CTC table and single-cell expression interpretation |
| DIA-NN / MaxQuant / OpenMS-style upstream routes | Advisory external | mzML/vendor raw files or protein/peptide abundance matrices | Plasma or extracellular-vesicle proteomics preprocessing and matrix-level review |
LLM Engines For Agent Interaction¶
These engines are used for natural-language understanding and user assistance. They do not replace the deterministic legality checks, method registry, or local analysis code.
| Backend | Selection | Use |
|---|---|---|
| OpenAI GPT | auto (currently gpt-6-luna) |
Default economical tier |
| OpenAI GPT | gpt-6-sol |
Explicit advanced tier |
| OpenAI GPT | gpt-6-astra |
Explicit flagship tier |
| Offline diagnostics | /llm off |
No model calls; not conversational intelligence |
The same adapter handles user messages, domain context, task and result summaries. See OpenAI configuration for the current policy.
Practical Reading Order¶
- Use this page for a global capability inventory.
- Use Blood-Signal Encoding for encoder defaults and accepted input formats.
- Use Liquid-Biopsy Method Advisor for external method selection details and references.
- Use CLI Entrypoints or Python API for reproducible command/API calls.
Current Web interaction guide¶
For the current interaction model and screenshots, use the workspace walkthrough, image/result controls and reviewed skills. They distinguish inspection, proposed follow-up, authorized execution and reviewed preferences.