Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Sustaining a national surgical training programme during the COVID-19 pandemic.

10.1302/2633-1462.15.BJO-2020-0019Bone Jt Open1598-10

The geographic distributions and complex genetic relationships among four Sorghum taxa identified in Taiwan

The genus Sorghum consists of 25 species, including Sorghum bicolor (L.) Moench, one of the top five cereal crops cultivated globally, and S. halepense, one of the most noxious weeds. Weedy Sorghum possesses outstanding adaptability and drought tolerance thrives in diverse environments and becomes an invasive plant worldwide. Taiwan is a unique place possessing suitable habitats for four Sorghum taxa, S. bicolor ssp. bicolor, var. technicum, ssp. verticilliflorum and S. halepense, which were identified by key morphological features. The four Sorghum taxa showed distinct geographic distributions, revealing that invasiveness was influenced by their own characteristics and human activities. The sporadic distributions of cultivated S. bicolor ssp. bicolor and var. technicum may be attributed to human disturbance and agricultural activities. The rhizomatous S. halepense was widely distributed and showed the highest genetic diversity (He &gt; 0.776) among the four taxa, with its strong adaptation to various environments threatening the agricultural practices and ecosystem in Taiwan. In contrast, the newly naturalised S. bicolor ssp. verticilliflorum was confined to and dominant in southern Taiwan, with the lowest genetic diversity (He &lt; 0.272). Significant genetic differentiation (F-ST = 0.5207) between the two ssp. verticilliflorum subpopulations was associated with natural geographic isolation. This study concretely elucidated the geographic distributions, genetic diversity and relatedness of invasive and escaped Sorghum taxa, indicating the potential aggressiveness and hazard of weedy Sorghum in Taiwan

CaproGlu : multifunctional tissue adhesive platform

Driven by the clinical need for a strong tissue adhesive with elastomeric material properties, a departure from legacy crosslinking chemistries was sought as a multipurpose platform for tissue mending. A fresh approach to bonding wet substrates has yielded a synthetic biomaterial that overcomes the drawbacks of free-radical and nature-inspired bioadhesives. A food-grade liquid polycaprolactone grafted with carbene precursors yields CaproGlu. The first-of-its-kind low-viscosity prepolymer is VOC-free and requires no photoinitiators. Grafted diazirine end-groups form carbene diradicals upon low energy UVA (365 nm) activation that immediately crosslink tissue surfaces; no pre-heating or animal-derived components are required. The hydrophobic polymeric environment enables metastable functional groups not possible in formulations requiring solvents or water. Activated diazirine within CaproGlu is uniquely capable of crosslinking all amino acids, even on wet tissue substrates. CaproGlu undergoes rapid liquid-to-biorubber transition within seconds of UVA exposure–features not found in any other bioadhesive. The exceptional shelf stability of CaproGlu allows gamma sterilization with no change in material properties. CaproGlu wet adhesiveness is challenged against current unmet clinical needs: anastomosis of spliced blood vessels, anesthetic muscle patches, and human platelet-mediating coatings. The versatility of CaproGlu enables both organic and inorganic composites for future bioadhesive platforms.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)Published versionNTU-Surgery ACP, Strategic Joint Research Fund (SJRF): Fast, 2 min surgical procedure for splicing of blood vessels; Singapore General Hospital Research Grant (SRGOF16Jan29): Dynamic release of local anaesthetics through novel tissue adhesives; Ministry of Education Tier 1 Grant: Coil Expanding Layers (COELS) For Intravascular Repairs; Ministry of Education Tier 2 Grant: Tailored soft-tissue bioadhesives for site-specific therapy (MOE2012-T2-2-046) & CaproGlu, Double sided wet-tissue adhesives (MOE2018-T2-2-114); NTU-Northwestern Institute for Nanomedicine Grant: 3D-Printing of Electro-Curing Nanocomposite Living Electrodes for Cardiac Tissue Regeneration; NTUitive POC (Gap) Fund Aesthetic Applications of CaproGlu Bioadhesives NGF/2018/05/; A*Star IAF PP Grant (H19/01/a0/0II9): CathoGlu Bioadhesivespreventing catheter extravasation and skin infections. JVH acknowledges support for the solid state NMR instrumentation at Warwick used in this research which was funded by EPSRC (grants EP/M028186/1 and EP/K024418/1) the University of Warwick, and the Birmingham Science City AM1 and AM2 projects which were supported by Advantage West Midlands (AWM) and the European Regional Development Fund (ERDF)

FRET efficiency and distance of the DNA duplex alone or bound to Sso7c4 in bulk FRET experiments.

<p>FRET efficiency and distance of the DNA duplex alone or bound to Sso7c4 in bulk FRET experiments.</p