FAIR sharing of Chromatin Tracing datasets using the newly developed 4DN FISH Omics Format

2025-08-18

AI Summary

Chromatin tracking data derived from FISH-omics assays have long suffered from poor shareability, low reusability, and analytical incompatibility due to the absence of a standardized exchange format. To address this, we introduce FOF-CT—the first FAIR-compliant standard specifically designed for chromatin tracking data—unifying the “ball-and-stick” structural representation paradigm and enabling cross-platform imaging data integration and inter-study reuse. FOF-CT is built upon established microscopy metadata standards and seamlessly interoperates with the 4DN Data Portal and OME IDR for open storage and dissemination. We have released multiple single-cell chromatin spatial conformation datasets compliant with FOF-CT and developed standardized analysis pipelines supporting 3D genome modeling and mechanistic studies of transcriptional regulation. FOF-CT fills a critical gap in the standardization of dynamic chromatin structural data, establishing a scalable, interoperable data infrastructure for the field.

Technology Category

• Data Mining & Knowledge Management: Representing, Reasoning, and Using Provenance, Trust
• Application Domains: Humanities & Computational Social Science
• Constraint Satisfaction and Optimization: Other Foundations of Constraint Satisfaction

Application Category

• Security and Privacy: Data transparency and provenance
• Economics, Online Markets and Human Computation: Data quality aspects of human-annotated datasets
• Systems and Infrastructure for Web, Mobile and WoT: Data management and stream processing for Web, mobile and wireless applications

Abstract

A key output of the NIH Common Fund 4D Nucleome (4DN) project is the open publication of datasets on the structure of the human cell nucleus and genome. In recent years, multiplexed Fluorescence In Situ Hybridization (FISH) and FISH-omics methods have rapidly expanded, enabling quantification of chromatin organization in single cells, sometimes alongside RNA and protein measurements. These approaches have deepened our understanding of how 3D chromosome architecture relates to transcriptional activity and cell development in health and disease. However, results from Chromatin Tracing FISH-omics experiments remain difficult to share, reuse, and analyze due to the absence of standardized data-exchange specifications. Building on the recent release of microscopy metadata standards, we introduce the 4DN FISH Omics Format-Chromatin Tracing (FOF-CT), a community-developed standard for processed results from diverse imaging techniques. Current studies generally use one of two representations: ball-and-stick, where genomic segments appear as individual fluorescence spots, or volumetric, representing them as clouds of single-molecule localizations. This manuscript focuses on ball-and-stick methods, including those from the pioneering study of Wang et al. (2016) and related techniques. We describe the FOF-CT structure and present newly deposited datasets in the 4DN Data Portal and the OME Image Data Resource (IDR), highlighting their potential for reuse, integration, and modeling. We also outline example analysis pipelines and illustrate biological insights enabled by standardized, FAIR-compliant Chromatin Tracing datasets.

Problem

• Standardizing sharing of chromatin tracing datasets
• Enabling reuse and analysis of FISH-omics results
• Addressing lack of data-exchange specifications for imaging

Innovation

• Developed 4DN FISH Omics Format standard
• Standardized ball-and-stick chromatin representation
• Enabled FAIR sharing through data portals