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Biology subjects

Kitchell, L. M.

Publications and source records attributed to Kitchell, L. M..

3 recordsLinked to original sources

Local graph-motif features improve gene interaction network prediction

Gene interaction networks specify how genes interact to produce an organisms phenotype. These networks are often incomplete due to absent or unobserved information. Predicting these missing links is critical for many applications, including genome-wide association studies and phenotype prediction. Efforts have previously applied graph neural networks (GNNs) to this missing-link prediction problem, but these techniques too have limitations when the sparsity of the networks is very high. Here, we apply a novel feature engineering technique that uses local graph motif incidence to enhance the feature set for variational graph autoencoders (VGAE). We compare the performance of our technique against state-of-the-art approaches, and then progressively hide more and more of the original graph edges. Our results show that VGAEs with our local-area motif prevalence (LAMP) features outperform state-of-the-art node embeddings for a wide range of missing edges on both a benchmark and a biological dataset. We also observe that this combined VGAE and LAMP technique has the potential to facilitate the search for novel genetic interactions in an experimental adaptive sampling context with far fewer samples. Improvements to gene interaction imputation can lower the barrier to new pharmaceutical and epidemiological discoveries by revealing hidden gene interactions that steer the development of potential drug targets.

bioinformatics↗

NEURD: A mesh decomposition framework forautomated proofreading and morphologicalanalysis of neuronal EM reconstructions

We are now in the era of millimeter-scale electron microscopy (EM) volumes collected at nanometer resolution (Shapson-Coe et al., 2021; Consortium et al., 2021). Dense reconstruction of cellular compartments in these EM volumes has been enabled by recent advances in Machine Learning (ML) (Lee et al., 2017; Wu et al., 2021; Lu et al., 2021; Macrina et al., 2021). Automated segmentation methods produce exceptionally accurate reconstructions of cells, but post-hoc proofreading is still required to generate large connectomes free of merge and split errors. The elaborate 3-D meshes of neurons in these volumes contain detailed morphological information at multiple scales, from the diameter, shape, and branching patterns of axons and dendrites, down to the fine-scale structure of dendritic spines. However, extracting these features can require substantial effort to piece together existing tools into custom workflows. Building on existing open-source software for mesh manipulation, here we present "NEURD", a software package that decomposes meshed neurons into compact and extensively-annotated graph representations. With these feature-rich graphs, we automate a variety of tasks such as state of the art automated proofreading of merge errors, cell classification, spine detection, axon-dendritic proximities, and other annotations. These features enable many downstream analyses of neural morphology and connectivity, making these massive and complex datasets more accessible to neuroscience researchers focused on a variety of scientific questions.

neuroscience↗

NeuVue: A Framework and Workflows for High-Throughput Electron Microscopy Connectomics Proofreading

Connectomic reconstruction from large image volumes produces segmentation and synaptic-assignment errors that must be resolved to support downstream analyses. As datasets have grown larger and teams more distributed, proofreading has become a critical operational bottleneck. Workflows for proofreading and error correction have not scaled commensurately with connectomic data production and may not accommodate heterogeneous proofreader expertise and machine-generated candidate edits. New tools are therefore needed to organize, prioritize, and coordinate proofreading at volume scale. Here we present NeuVue, a task-management and prioritization framework that operationalizes proofreading through atomic, auditable tasks for individual and team review, multistage routing across proofreader cohorts, performance and volume-state tracking, and integration with community annotation, visualization, and analysis services. We report the use of NeuVue across two volumetric datasets, supporting scalable proofreading by over forty proofreaders and producing over fifty thousand edits. NeuVue provides a reproducible human-in-the-loop framework for generating, validating, and maintaining large connectomic datasets.

neuroscience↗