A finished clone-based assembly of the mouse genome reveals extensive recent sequence duplication during recent evolution and rodent-specific expansion of certain gene families. Newly assembled duplications contain protein-coding genes that are mostly involved in reproductive function.

Variation in genome structure is an important source of human genetic polymorphism: It affects a large proportion of the genome and has a variety of phenotypic consequences relevant to health and disease. In spite of this, human genome structure variation is incompletely characterized due to a lack of approaches for discovering a broad range of structural variants in a global, comprehensive fashion. We addressed this gap with Optical Mapping, a highthroughput, high-resolution single-molecule system for studying genome structure. We used Optical Mapping to create genomewide restriction maps of a complete hydatidiform mole and three lymphoblast-derived cell lines, and we validated the approach by demonstrating a strong concordance with existing methods. We also describe thousands of new variants with sizes ranging from kb to Mb. structural variation | copy number variation | optical mapping | single-molecule genomics | genome assembly R ecent reports (1-11) have firmly established genome structural variation as an important and pervasive source of genetic polymorphism. Since the initial reports (1, 2) of widespread copy-number variation between the genomes of phenotypically normal individuals, investigators have applied hybridizationbased methods (3, 7, 9, 11), computational approaches (5, 6), clone paired-end sequencing (4, 10) and most recently a pairedend sequencing by synthesis approach (8) to the discovery and characterization of structural polymorphism. Others have described phenotypic consequences of these variants, including associations with myocardial infarction, neuroblastoma, autism, and schizophrenia (reviewed recently in ref. 12). Finally, their consistent association with segmental duplications and other classes of repeats (13) provides a mechanistic explanation for their origin (14) and points to a previously unappreciated role in evolution (15) as well as disease.Unfortunately, despite all efforts, a comprehensive picture of genome structure polymorphism has not yet emerged. Current genome-wide studies of structural variation manifest only modest concordance, possibly due to ascertainment biases arising from the techniques employed. For example, hybridization-based methods (2,3,7,9,11,16) are subject to nonspecific hybridization in repeat-rich regions, while clone-based strategies (4,8,10) are limited by maximum clone insert sizes and a wide clone size distribution relative to the events they are trying to detect. More recently, several entire human genomes were sequenced using high-throughput methods (17)(18)(19)(20), but the difficulty of interrogating repeat-rich regions is compounded by these systems' short read lengths.In an effort to overcome these challenges, we have applied Optical Mapping to the problem of discerning structural variation in normal human genomes. Optical Mapping (21-35) is a highthroughput system that combines single-molecule measurements with dedicated computational analysis to produce ordered restriction maps from individual molecules of genomic DNA: essentially, a singl...

A deficient interferon response to SARS-CoV-2 infection has been implicated as a determinant of severe COVID-19. To identify the molecular effectors that govern interferon control of SARS-CoV-2 infection, we conducted a large-scale gain-of-function analysis that evaluated the impact of human interferon stimulated genes (ISGs) on viral replication. A limited subset of ISGs were found to control viral infection, including endosomal factors inhibiting viral entry, RNA binding proteins suppressing viral RNA synthesis, and a highly enriched cluster of ER-Golgi-resident ISGs inhibiting viral assembly-egress. These included broad-acting antiviral ISGs, and eight ISGs that specifically inhibited SARS-CoV-2 and -1 replication. Amongst the broad-acting ISGs was BST2/tetherin, which impeded viral release, and is antagonized by SARS-CoV-2 Orf7a protein. Overall, these data illuminate a set of ISGs that underlie innate immune control of SARS-CoV-2/-1 infection, which will facilitate the understanding of host determinants that impact disease severity and offer potential therapeutic strategies for COVID-19.

As biomedical imaging datasets expand, deep neural networks are considered vital for image processing, yet community access is still limited by setting up complex computational environments and availability of high-performance computing resources. We address these bottlenecks with CDeep3M, a ready-to-use image segmentation solution employing a cloud-based deep convolutional neural network. We benchmark CDeep3M on large and complex two-dimensional and three-dimensional imaging datasets from light, X-ray, and electron microscopy.

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