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68Metabolomics data are difficult to find and reuse, even in public repositories. We, therefore, developed the 69Reanalysis of Data User (ReDU) interface (https://redu.ucsd.edu/), a community-and data-driven approach that 70 solves this problem at the repository scale. ReDU enables public data discovery and co-or re-analysis via 71 uniformly formatted, publicly available MS/MS data and metadata in the Global Natural Product Social Molecular 72Networking Platform (GNPS), consistent with findable, accessible, interoperable, and reusable (FAIR) 73principles. 1 74 75 76 Many simple but important questions can be asked using repository-scale public data. For example, what 77 human biospecimen or sampling location is best for detecting a given drug? Or what molecules are found in 78 humans <2 years old? Current metabolomics repositories typically require manual navigation and conversion of 79 thousands of different vendor-formatted files with inconsistent metadata formats, and developing data integration 80 algorithms, greatly complicating analyses. 81 Results and DiscussionReDU addresses FAIR principles by enabling users to find and choose files (Fig 1a). This is possible 82because ReDU formats sample information consistently via a template and drag-and-drop validator backed by 83 standard controlled vocabularies and ontologies (e.g. NCBI taxonomy, 2 UBERON 3, Disease Ontology 4 and MS 84 ontology), and includes geographical location (important for natural products and environmental samples). ReDU 85 automatically uses all public data in the GNPS/MassIVE repository that has the corresponding ReDU-compliant 86 sample information. 34,087 files in GNPS are ReDU-compatible including natural and human-built environments, 87human and animal tissues, biofluids, food, and other data from around the world (Fig 1f), analyzed using different 88 instruments, ionization methods, sample preparation methods, etc. From the 103,230,404 million MS/MS spectra 89 included in ReDU, 4,528,624 spectra were annotated (rate of 4.39% with settings yielding ~1% FDR) as one of 90 13,217 unique chemicals (Table S1). 5,6,7 91 Uniformity of data and sample information in ReDU enables metadata-based and repository-scale 92 analyses ( Fig. 1b-g). Chemical explorer enables selection of a molecule and retrieval of its associations with the 93 metadata, i.e. sample information association. For instance, selecting 12-ketodeoxycholic acid (filtering to 94 include human feces) revealed it was observed after infancy (Fig 1c), whereas cholic acid displayed the opposite 95 trend, coupled to the developing microbiome. Similarly, rosuvastatin was found in adults matching prescription 96 demographics. Another approach enabled is chemical enrichment analysis. For example, human blood, feces, 97 and urine differed by bilirubin, urobilin, and stercobilin (Fig 1d). Bilirubin was more frequently annotated in blood, 98and urobilin and stercobilin were most often annotated in feces. 8 Similarly, comparison of bacterial cultures 99 revealed differences in annotati...

We evaluated six pairs of conjoined twins: four pairs were dicephalus, and two were of the ischiopagus type. In three of the four dicephalus pairs, the right twin had an abnormality of laterality that included a right aortic arch, reversed great vessel orientation, bilateral right-sided isomerism of the lungs, asplenia, and situs inversus of the viscera. The left twin had normal great vessel orientation and situs solitus in each case. The finding that was unique in these three dicephalus twin pairs was their fused hearts, which were similar in orientation and configuration. The fourth dicephalus twin pair had one normally rotated heart, which was located in the midline and had normally placed chambers and great vessels. Each twin of this pair had normal visceral situs. In the two pairs of ischiopagus twins, each pair had two separate hearts, with normal cardiac structure and great vessel relationships. The viscera expressed normal laterality. Documentation of a defect in laterality in the right twin in three conjoined twin pairs with fusion of the hearts, combined with the presence of normal laterality in three pairs without cardiac fusion, has implications regarding the mechanisms leading to laterality of the human embryo. We suggest that rotation of the heart initiates the embryo's process of lateralization and that the laterality defects of the viscera seen in the right twin are a result of their abnormal cardiac rotation.

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Virus infection is frequently characterized using bulk cell populations. How these findings correspond to infection in individual cells remains unclear. Here, we integrate high-dimensional single-cell approaches to quantify viral and host RNA and protein expression signatures using de novo infection with a well-characterized model gammaherpesvirus. While infected cells demonstrated genome-wide transcription, individual cells revealed pronounced variation in gene expression, with only 9 of 80 annotated viral open reading frames uniformly expressed in all cells, and a 1000-fold variation in viral RNA expression between cells. Single-cell analysis further revealed positive and negative gene correlations, many uniquely present in a subset of cells. Beyond variation in viral gene expression, individual cells demonstrated a pronounced, dichotomous signature in host gene expression, revealed by measuring host RNA abundance and post-translational protein modifications. These studies provide a resource for the high-dimensional analysis of virus infection, and a conceptual framework to define virus infection as the sum of virus and host responses at the single-cell level.