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Mechanical deformations of DNA such as bending are ubiquitous and have been implicated in diverse cellular functions.sup.1. However, the lack of high-throughput tools to measure the mechanical properties of DNA has limited our understanding of how DNA mechanics influence chromatin transactions across the genome. Here we develop 'loop-seq'--a high-throughput assay to measure the propensity for DNA looping--and determine the intrinsic cyclizabilities of 270,806 50-base-pair DNA fragments that span Saccharomyces cerevisiae chromosome V, other genomic regions, and random sequences. We found sequence-encoded regions of unusually low bendability within nucleosome-depleted regions upstream of transcription start sites (TSSs). Low bendability of linker DNA inhibits nucleosome sliding into the linker by the chromatin remodeller INO80, which explains how INO80 can define nucleosome-depleted regions in the absence of other factors.sup.2. Chromosome-wide, nucleosomes were characterized by high DNA bendability near dyads and low bendability near linkers. This contrast increases for deeper gene-body nucleosomes but disappears after random substitution of synonymous codons, which suggests that the evolution of codon choice has been influenced by DNA mechanics around gene-body nucleosomes. Furthermore, we show that local DNA mechanics affect transcription through TSS-proximal nucleosomes. Overall, this genome-scale map of DNA mechanics indicates a 'mechanical code' with broad functional implications. A high-throughput, chromosome-wide analysis of DNA looping reveals its contribution to the organization of chromatin, and provides insight into how nucleosomes are deposited and organised de novo., Author(s): Aakash Basu [sup.1] [sup.2] , Dmitriy G. Bobrovnikov [sup.1] , Zan Qureshi [sup.3] , Tunc Kayikcioglu [sup.2] [sup.4] , Thuy T. M. Ngo [sup.2] [sup.4] , Anand Ranjan [sup.5] [...]

Burkholderia cepacia is the type species of the genus Burkholderia and is a ubiquitous multidrug-resistant, motile, non-glucose-fermenting, gram-negative organism found in water and soil (1). The B. cepacia complex (BCC) [...]

Medulloblastoma is a malignant childhood cerebellar tumour type that comprises distinct molecular subgroups. Whereas genomic characteristics of these subgroups are well defined, the extent to which cellular diversity underlies their divergent biology and clinical behaviour remains largely unexplored. Here we used single-cell transcriptomics to investigate intra- and intertumoral heterogeneity in 25 medulloblastomas spanning all molecular subgroups. WNT, SHH and Group 3 tumours comprised subgroup-specific undifferentiated and differentiated neuronal-like malignant populations, whereas Group 4 tumours consisted exclusively of differentiated neuronal-like neoplastic cells. SHH tumours closely resembled granule neurons of varying differentiation states that correlated with patient age. Group 3 and Group 4 tumours exhibited a developmental trajectory from primitive progenitor-like to more mature neuronal-like cells, the relative proportions of which distinguished these subgroups. Cross-species transcriptomics defined distinct glutamatergic populations as putative cells-of-origin for SHH and Group 4 subtypes. Collectively, these data provide insights into the cellular and developmental states underlying subtype-specific medulloblastoma biology. Characterization of medulloblastoma tissues using single-cell transcriptomics shows that the different molecular subtypes consist of distinct developmental phenotypes., Author(s): Volker Hovestadt [sup.1] [sup.2] , Kyle S. Smith [sup.3] , Laure Bihannic [sup.3] , Mariella G. Filbin [sup.1] [sup.2] [sup.4] , McKenzie L. Shaw [sup.1] [sup.2] [sup.4] , Alicia [...]

Author(s): Muin J. Khoury 1,*, Gregory L. Armstrong 2, Rebecca E. Bunnell 3, Juliana Cyril 4, Michael F. Iademarco 5 Summary points The field of precision public health (PPH) has [...]

Advances in genomics and imaging are reviving a fading discipline. Advances in genomics and imaging are reviving a fading discipline., Author(s): Heidi Ledford Author Affiliations: 3D imaging offers new views of these antirrhinum (snapdragon) buds. Credit: Karen Lee/Xana Rebocho/John Innes Centre An Antirrhinum flower bud. The lost art of looking [...]

Efforts to track SARS-CoV-2 sequences have helped identify worrying variants -- but researchers are blind to emerging mutations in some regions. Efforts to track SARS-CoV-2 sequences have helped identify worrying variants -- but researchers are blind to emerging mutations in some regions., Author(s): David Cyranoski Author Affiliations: Alarming COVID variants show vital role of genomic surveillance The United Kingdom entered its third lockdown after genomic surveillance detected a fast-spreading SARS-CoV-2 variant. Credit: [...]

Despite three decades of successful, predominantly phenotype-driven discovery of the genetic causes of monogenic disorders (1), up to half of children with severe developmental disorders of probable genetic origin remain without a genetic diagnosis. Particularly challenging are those disorders rare enough to have eluded recognition as a discrete clinical entity, those with highly variable clinical manifestations, and those that are difficult to distinguish from other, very similar, disorders. Here we demonstrate the power of using an unbiased genotype-driven approach (2) to identify subsets of patients with similar disorders. By studying 1,133 children with severe, undiagnosed developmental disorders, and their parents, using a combination of exome sequencing (3-11) and array-based detection of chromosomal rearrangements, we discovered 12 novel genes associated with developmental disorders. These newly implicated genes increase by 10% (from 28% to 31%) the proportion of children that could be diagnosed. Clustering of missense mutations in six of these newly implicated genes suggests that normal development is being perturbed by an activating or dominant-negative mechanism. Our findings demonstrate the value of adopting a comprehensive strategy, both genome-wide and nationwide, to elucidate the underlying causes of rare genetic disorders., The Deciphering Developmental Disorders Study * We established a network to recruit 1,133 children (median age 5.5 years, Extended Data Fig. 1a) with diverse, severe undiagnosed developmental disorders, through all [...]

Although ≅ 200 imported cases of dengue fever have recently been reported in Japan (1), an autochthonous case had not been confirmed there for 70 years (2). However, on August [...]

Melioidosis is thought to be caused predominantly by percutaneous inoculation with the bacterium Burkholderia pseudomallei; however, inhalation, aspiration, and ingestion of the bacterium can also occur (1). Although an evidence-based [...]

In genomics, polymerase chain reaction (PCR) is used to amplify the amount of DNA and increase the signal above the limit of detection. This approach is not applicable to proteomics, [...]