Chromosome-scale and haplotype-resolved genome assembly of a tetraploid potato cultivar

Potato is the most widely produced tuber crop worldwide. However, reconstructing the four haplotypes of its autotetraploid genome remained an unsolved challenge. Here, we report the 3.1 Gb haplotype-resolved (at 99.6% precision), chromosome-scale assembly of the potato cultivar ‘Otava’ based on high-quality long reads, single-cell sequencing of 717 pollen genomes and Hi-C data. Unexpectedly, ~50% of the genome was identical-by-descent due to recent inbreeding, which was contrasted by highly abundant structural rearrangements involving ~20% of the genome. Among 38,214 genes, only 54% were present in all four haplotypes with an average of 3.2 copies per gene. Taking the leaf transcriptome as an example, 11% of the genes were differently expressed in at least one haplotype, where 25% of them were likely regulated through allele-specific DNA methylation. Our work sheds light on the recent breeding history of potato, the functional organization of its tetraploid genome and has the potential to strengthen the future of genomics-assisted breeding

A Balloon-Borne Millimeter-Wave Telescope for Cosmic Microwave Background Anisotropy Measurements

We report on the characteristics and design details of the Medium Scale Anisotropy Measurement (MSAM), a millimeter-wave, balloon-borne telescope that has been used to observe anisotropy in the Cosmic Microwave Background Radiation (CMBR) on 0\fdg5 angular scales. The gondola is capable of determining and maintaining absolute orientation to a few arcminutes during a one-night flight. Emphasis is placed on the optical and pointing performance as well as the weight and power budgets. We also discuss the total balloon/gondola mechanical system. The pendulation from this system is a ubiquitous perturbation on the pointing system. A detailed understanding in these areas is needed for developing the next generation of balloon-borne instruments.Comment: 37 pages, 15 figures, uses BoxedEPS.te

The dipole corrector magnets for the RHIC fast global orbit feedback system

The recently completed RHIC fast global orbit feedback system uses 24 small 'window-frame' horizontal dipole correctors. Space limitations dictated a very compact design. The magnetic design and modelling of these laminated yoke magnets is described as well as the mechanical implementation, coil winding, vacuum impregnation, etc. Test procedures to determine the field quality and frequency response are described. The results of these measurements are presented and discussed. A small fringe field from each magnet, overlapping the opposite RHIC ring, is compensated by a correction winding placed on the opposite ring's magnet and connected in series with the main winding of the first one. Results from measurements of this compensation scheme are shown and discussed

Cell type-specific transcriptomics of esophageal adenocarcinoma as a scalable alternative for single cell transcriptomics

Single-cell transcriptomics have revolutionized our understanding of the cell composition of tumors and allowed us to identify new subtypes of cells. Despite rapid technological advancements, single-cell analysis remains resource-intense hampering the scalability that is required to profile a sufficient number of samples for clinical associations. Therefore, more scalable approaches are needed to understand the contribution of individual cell types to the development and treatment response of solid tumors such as esophageal adenocarcinoma where comprehensive genomic studies have only led to a small number of targeted therapies. Due to the limited treatment options and late diagnosis, esophageal adenocarcinoma has a poor prognosis. Understanding the interaction between and dysfunction of individual cell populations provides an opportunity for the development of new interventions. In an attempt to address the technological and clinical needs, we developed a protocol for the separation of esophageal carcinoma tissue into leukocytes (CD45+), epithelial cells (EpCAM+), and fibroblasts (two out of PDGFRα, CD90, anti-fibroblast) by fluorescence-activated cell sorting and subsequent RNA sequencing. We confirm successful separation of the three cell populations by mapping their transcriptomic profiles to reference cell lineage expression data. Gene-level analysis further supports the isolation of individual cell populations with high expression of CD3, CD4, CD8, CD19, and CD20 for leukocytes, CDH1 and MUC1 for epithelial cells, and FAP, SMA, COL1A1, and COL3A1 for fibroblasts. As a proof of concept, we profiled tumor samples of nine patients and explored expression differences in the three cell populations between tumor and normal tissue. Interestingly, we found that angiogenesis-related genes were upregulated in fibroblasts isolated from tumors compared with normal tissue. Overall, we suggest our protocol as a complementary and more scalable approach compared with single-cell RNA sequencing to investigate associations between clinical parameters and transcriptomic alterations of specific cell populations in esophageal adenocarcinoma

The genetics of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease caused by the interaction of genetic susceptibility and environmental influences. There is increasing evidence that genes link to disease pathogenesis and heterogeneity by causing variation in protease anti-protease systems, defence against oxidative stress and inflammation. The main methods of genomic research for complex disease traits are described, together with the genes implicated in COPD thus far, their roles in disease causation and the future for this area of investigation

Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease

Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the 'preclinical' stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome.CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n = 24) and cognitively normal controls (CDR 0) (n = 24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs) to a larger independent cohort (n = 292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85-0.94 95% confidence interval [CI]) and 0.88 (0.81-0.94 CI), respectively.Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding subject enrollment and monitoring disease progression. Further studies will be required to validate this panel and evaluate its potential for distinguishing AD from other dementing conditions

Omics-based molecular techniques in oral pathology centred cancer: Prospect and challenges in Africa

: The completion of the human genome project and the accomplished milestones in the human proteome project; as well as the progress made so far in computational bioinformatics and “big data” processing have contributed immensely to individualized/personalized medicine in the developed world.At the dawn of precision medicine, various omics-based therapies and bioengineering can now be applied accurately for the diagnosis, prognosis, treatment, and risk stratifcation of cancer in a manner that was hitherto not thought possible. The widespread introduction of genomics and other omics-based approaches into the postgraduate training curriculum of diverse medical and dental specialties, including pathology has improved the profciency of practitioners in the use of novel molecular signatures in patient management. In addition, intricate details about disease disparity among diferent human populations are beginning to emerge. This would facilitate the use of tailor-made novel theranostic methods based on emerging molecular evidences

Chromosome-scale and haplotype-resolved genome assembly of a tetraploid potato cultivar

Potato is the third most important food crop in the world. Despite its social and economic importance, the autotetraploid genome of cultivated potato has not been assembled yet. The distinct reconstruction all of four haplotypes remained an unsolved challenge. Here, we report the 3.1 Gb haplotype-resolved, chromosome-scale assembly of the autotetraploid potato cultivar, Otava. We assembled the genome with high-quality long reads coupled with single-cell sequencing of 717 pollen genomes and chromosome conformation capture data at a haplotyping precision of 99.6%. Unexpectedly, we found that almost 50% of the tetraploid genome were identical-by-descent with at least one of the other haplotypes. This high level of inbreeding contrasted with the extreme level of structural rearrangements encompassing nearly 20% of the genome. Overall, we annotated 148,577 gene models, where only 54% of the genes were present in all four haplotypes with an average of 3.2 copies per gene. Our work showcases how accurate assemblies of complex and partially inbred autotetraploid genomes can be generated. The newly established resource gives novel insights in the breeding history of autotetraploid potato and has the potential to change the future of genomics-assisted potato breeding.Competing Interest StatementThe authors have declared no competing interest

A Digital On-Demand Video Service Supporting Content-Based Queries

Video-on-demand represents a key demonstrative application for enabling multimedia technology in communication, database, and interface research. This application requires solving a number of diverse technical problems including the data synchronization problem for time-dependent data delivery. In this paper we describe the general requirements of video-on-demand and introduce a system supporting content-based retrieval and playback for the structure and content of digital motion pictures. In our model we capture domain-specific information for motion pictures and provide access to individual scenes of movies through queries on a temporal database. We describe our implementation of this service using existing workstation and storage technology. Keywords: Multimedia databases, video-on-demand, applications, temporal data management, content-based retrieval. 1 Introduction Future multimedia information systems will have a dramatic effect on the dissemination of information to individu..