{
  "abstract": "MOTIVATION Single-nucleus resolution multiome (snMultiome) assays concurrently profile gene expression and chromatin accessibility in the same nucleus. Yet regulatory inference from such analyses are difficult to scale, audit, and reproduce; moreover, as a field, snMultiomics and its toolset remains far from standardized. To address these challenges we developed FORGE, a configureable Nextflow workflow that carries paired data from raw counts and fragments through regulatory network inference with a comprehensive differential testing suite. Execution is containerized, tracks provenance, robust to interruption, optimized for cluster-based compute environments, and allows for nuanced customization of specific processes. SUMMARY Single-nucleus multiome assays jointly profile gene expression and chromatin accessibility, yet their analysis typically requires bespoke chaining of modality-specific tools, creating barriers to reproducibility, scalability, and regulatory interpretation. We present FORGE (Flow Orchestrated Regulatory Genomics Engine), a configurable workflow that automates standalone snRNA-seq and snATAC-seq analysis, integrates the pair through complementary linear and nonlinear latent-variable models, and carries them through regulatory-network inference and differential testing. We evaluated FORGE on four human and mouse datasets spanning blood, brain, and kidney and two multiome chemistries, including a twelve-sample CRND8 Alzheimers disease cohort. We report cross-modal agreement alongside missing-modality reconstruction and an accounting of computational cost. In the Alzheimer's cohort, FORGE nominated a glial Mef2c-associated program defensible across expression, co-accessibility, footprinting, and eRegulon evidence. In human PBMC, FORGE layered evidence models also provide nuanced interpretations that largely corroborate previously published regulatory links while also proposing an additional CD83 myeloid module.",
  "abstract_shown": true,
  "affiliations": [
    "University of California Irvine"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "L. E. Solano"
    },
    {
      "name": "N. Rahimzadeh"
    },
    {
      "name": "Z. Shi"
    },
    {
      "affs": [
        0
      ],
      "name": "V. Swarup"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dsp8wdmmqr1qx.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.10.750690",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.10.750690v1.full",
  "id": "dsp8wdmmqr1qx",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.10.750690v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "bioinformatics"
    ],
    [
      "openalex",
      "1312|Single-cell and spatial transcriptomics"
    ]
  ],
  "openalex": "W7213403055",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.10.750690v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/dsp8wdmmqr1qx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:41Z",
      "native_id": "10.64898/2026.09.10.750690",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.10.750690v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "Flow Orchestrated Regulatory Genomics Engine (FORGE): A Configurable Nextflow Pipeline for End-to-End snMultiome Analysis",
  "title_text": "Flow Orchestrated Regulatory Genomics Engine (FORGE): A Configurable Nextflow Pipeline for End-to-End snMultiome Analysis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:22:41Z",
  "url": "https://research.draconitic.com/paper/dsp8wdmmqr1qx",
  "venue": "bioRxiv",
  "versions": []
}