{
  "abstract": "Differential gene expression rarely explains why certain genes, e.g. associated with tissue-specific manifestations of human disease, exert tissue-specific functions. To understand how gene expression and molecular context act in concert to drive tissue-specific gene function, we focus on Neurodevelopmental disorders (NDDs), for which underlying disease mechanisms are still poorly understood. We developed a computational framework that harmonizes and integrates spatiotemporal transcriptome datasets enabling us to systematically quantify preferential gene expression across tissues and developmental stages. Applying this pipeline to approximately 1,000 NDD-associated genes, we find that only about 10% show brain-preferential expression, with distinct gene clusters instead exhibiting significant upregulation in non-brain tissues. Investigation of these clusters reveals regulatory mechanisms that govern mitochondrial function to meet neurons' high energetic demands, which are mechanistically distinct from those employed by other energy-intensive tissues such as heart and skeletal muscle. Furthermore, by integrating tissue-agnostic protein-protein interaction data with our expression resource, we identify putative brain-specific interaction partners for 22 uniformly expressed NDD-associated genes. We experimentally validate these interactions for QRICH1 and demonstrate that disease-associated mutations disrupt them, providing a molecular hypothesis for how QRICH1 acquires brain-specific function and how its disruption might cause Ververi-Brady syndrome. Together, our findings highlight the importance of molecular context for brain-specific gene function in the context of neurodevelopmental disease. We provide a framework for dissecting molecular mechanisms of tissue-specific Mendelian-like disorders and for exploring how biological processes are adapted to tissue-specific needs.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Molecular Biology"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "M. Djokic"
    },
    {
      "name": "S. Karunanithi"
    },
    {
      "name": "M. Welzel"
    },
    {
      "name": "F. Kielisch"
    },
    {
      "affs": [
        0
      ],
      "name": "K. Luck"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7122pprsr8qv6.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.26.761783",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761783v1.full",
  "id": "7122pprsr8qv6",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761783v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "bioinformatics"
    ],
    [
      "openalex",
      "1311|Genetics and Neurodevelopmental Disorders"
    ]
  ],
  "openalex": "W7224015669",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761783v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7122pprsr8qv6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:48Z",
      "native_id": "10.64898/2026.10.26.761783",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761783v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioinformatics",
      "subfield": "bioinformatics"
    }
  ],
  "title": "Cellular context defines brain-specific functions of genes associated with neurodevelopmental disorders",
  "title_text": "Cellular context defines brain-specific functions of genes associated with neurodevelopmental disorders",
  "type": "preprint",
  "updated_at": "2026-10-30T12:29:48Z",
  "url": "https://research.draconitic.com/paper/7122pprsr8qv6",
  "venue": "bioRxiv",
  "versions": []
}