Spatial coherence in DNA barcode networks.

DNA barcode networks are the basis of sequencing-based microscopy, an emerging family of chemical imaging methods aiming to reconstruct spatial information, without optics, using sequencing technology. These methods capture microscopic spatial information by forming networks composed of many local chemical interactions, each marked by a unique, DNA-based barcode. However, the fundamental laws governing such networks are not yet understood, and spatial barcode networks are influenced by structural distortions such as false or shortcut edges. Current methods lack ground-truth-free tools to validate spatial quality, and we address this with a framework for topology-based quality control. We define a fundamental feature of spatial networks, spatial coherence, which quantifies geometric self-consistency in a network. By formalizing this relationship into quantitative metrics adapted from classical geometric rules, we could quantify spatial distortions by using only network data and show how these can be used as an optimization criterion to iteratively improve spatial reconstruction.