RT Journal Article SR Electronic T1 Image recovery from unknown network mechanisms for DNA sequencing-based microscopy JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.09.29.510142 DO 10.1101/2022.09.29.510142 A1 Bonet, David Fernandez A1 Hoffecker, Ian T. YR 2022 UL http://biorxiv.org/content/early/2022/09/30/2022.09.29.510142.abstract AB Imaging-by-sequencing methods are an emerging alternative to conventional optical micro- or nanoscale imaging. In these methods, molecular networks form through proximity-dependent association between DNA molecules carrying random sequence identifiers. DNA strands record pairwise associations such that network structure may be recovered by sequencing which, in turn, reveals the underlying spatial relationships between molecules comprising the network. Determining the computational reconstruction strategy that makes the best use of the information (in terms of spatial localization accuracy, robustness to noise, and scalability) in these networks is an open problem. We present a graph-based technique for reconstructing a diversity of molecular network classes in 2 and 3 dimensions without prior knowledge of their fundamental generation mechanisms. The model achieves robustness by obtaining an unbiased sampling of local and global network structure using random walks, making use of minimal prior assumptions. Images are recovered from networks in two stages of dimensionality reduction first with this structural discovery step followed by the manifold learning step. By breaking the process into stages, computational complexity could be reduced leading to fast and accurate performance. Our method represents a means by which diverse molecular network generation strategies could be unified with a common reconstruction framework.Competing Interest StatementThe authors have declared no competing interest.