Abstract
Motivation
Oxford Nanopore Technologies sequencing devices support adaptive sequencing, in which undesired reads can be ejected from a pore in real time. This feature allows targeted ...sequencing aided by computational methods for mapping partial reads, rather than complex library preparation protocols. However, existing mapping methods either require a computationally expensive base-calling procedure before using aligners to map partial reads or work well only on small genomes.
Results
In this work, we present a new streaming method that can map nanopore raw signals for real-time selective sequencing. Rather than converting read signals to bases, we propose to convert reference genomes to signals and fully operate in the signal space. Our method features a new way to index reference genomes using k-d trees, a novel seed selection strategy and a seed chaining algorithm tailored toward the current signal characteristics. We implemented the method as a tool Sigmap. Then we evaluated it on both simulated and real data and compared it to the state-of-the-art nanopore raw signal mapper Uncalled. Our results show that Sigmap yields comparable performance on mapping yeast simulated raw signals, and better mapping accuracy on mapping yeast real raw signals with a 4.4× speedup. Moreover, our method performed well on mapping raw signals to genomes of size >100 Mbp and correctly mapped 11.49% more real raw signals of green algae, which leads to a significantly higher F1-score (0.9354 versus 0.8660).
Availability and implementation
Sigmap code is accessible at https://github.com/haowenz/sigmap.
Supplementary information
Supplementary data are available at Bioinformatics online.
Abstract
Motivation
As a fundamental task in bioinformatics, searching for massive short patterns over a long text has been accelerated by various compressed full-text indexes. These indexes are able ...to provide similar searching functionalities to classical indexes, e.g. suffix trees and suffix arrays, while requiring less space. For genomic data, a well-known family of compressed full-text indexes, called FM-indexes, presents unmatched performance in practice. One major drawback of FM-indexes is that their locating operations, which report all occurrence positions of patterns in a given text, are not efficient, especially for the patterns with many occurrences.
Results
In this paper, we introduce a novel locating algorithm, FMtree, to fast retrieve all occurrence positions of any pattern via FM-indexes. When searching for a pattern over a given text, FMtree organizes the search space of the locating operation into a conceptual multiway tree. As a result, multiple occurrence positions of this pattern can be retrieved simultaneously by traversing the multiway tree. Compared with existing locating algorithms, our tree-based algorithm reduces large numbers of redundant operations and presents better data locality. Experimental results show that FMtree is usually one order of magnitude faster than the state-of-the-art algorithms, and still memory-efficient.
Availability and implementation
FMtree is freely available at https://github.com/chhylp123/FMtree.
Supplementary information
Supplementary data are available at Bioinformatics online.
Based on integral sliding mode control, a backstepping controller which combines the sliding mode control and backstepping technology is proposed for the problem of integrated guidance and control ...for missiles. The backstepping controller is designed based on the nominal model for the pitch channel model of integrated guidance and control. In order to eliminate the "computation explosion", the dynamic surface control strategy is employed by introducing a first-order filter to obtain the differential of the virtual control input. Then, a compensator based on integral sliding mode surface is used to improve robustness to the model uncertainties and external disturbances. By using the Lyapunov stability theorem, it is proved that the closed loop system is stable. Finally, the simulation results demonstrate the superiority and effectiveness of the control scheme.
The complete sequence of a human genome Nurk, Sergey; Koren, Sergey; Rhie, Arang ...
Science (American Association for the Advancement of Science),
04/2022, Volume:
376, Issue:
6588
Journal Article
Peer reviewed
Open access
Since its initial release in 2000, the human reference genome has covered only the euchromatic fraction of the genome, leaving important heterochromatic regions unfinished. Addressing the remaining ...8% of the genome, the Telomere-to-Telomere (T2T) Consortium presents a complete 3.055 billion-base pair sequence of a human genome, T2T-CHM13, that includes gapless assemblies for all chromosomes except Y, corrects errors in the prior references, and introduces nearly 200 million base pairs of sequence containing 1956 gene predictions, 99 of which are predicted to be protein coding. The completed regions include all centromeric satellite arrays, recent segmental duplications, and the short arms of all five acrocentric chromosomes, unlocking these complex regions of the genome to variational and functional studies.
The large molecular weight of polysaccharides limits their absorption and utilization by organisms, affecting their biological activities. In this study, we purified α-1,6-galactan from Cantharellus ...cibarius Fr. (chanterelle) and reduced its molecular weight from approximately 20 kDa to 5 kDa (named CCP) to increase its solubility and absorption. In APP/PS1 mice, CCP improved both spatial and non-spatial memory loss in Alzheimer's disease (AD) mice, as confirmed by the Morris water maze, step-down, step-through, and novel object recognition tests, and dampened the deposition of amyloid-β plaques, as assessed by immunohistochemical analysis. Proteomic analysis suggested that the neuroprotective effects of CCP are related to anti-neuroinflammation. Immunofluorescence analysis and western blotting confirmed that CCP attenuated AD-like symptoms partly by inhibiting neuroinflammation, which was related to the blocking of complement component 3. Our study provides theoretical support and experimental evidence for the future application of chanterelle-extracted polysaccharides in AD treatment, promoting the modern development of traditional medicines originating from natural polysaccharides.
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Capillary-array windows have garnered significant interest in the realm of plasma processing and semiconductor fabrication. One potential application of these windows is their use in enabling the ...transmission of optical radiation produced by plasma processing systems while simultaneously safeguarding the substrate being exposed to these radiation from damage caused by high-energy electrons, ions, and neutral particles generated in the plasma. The hypothesis of this study posits that capillary-array windows would exhibit superior optical transmission capabilities in the ultraviolet (UV) and vacuum-ultraviolet (VUV) range in comparison to solid thin films. Furthermore, it is believed that the transmission efficiency of the capillary-array windows can be maximized by optimizing their dimension and the experimental settings while still maintaining a substantial pressure differential between two regimes.Three types of capillary-array windows were considered, classified according to their pore size: nanoporous, microporous, and milliporous. The nanoporous capillary-array windows were found to behave similarly to solid thin films, with low transmission of optical radiation in the ultraviolet (UV) and vacuum-ultraviolet (VUV) range. In contrast, the microporous and milliporous capillary-array windows exhibited UV and VUV transmission efficiencies of up to approximately 58.93% and 44.87%, respectively.This work employed a fractional-factorial design method to investigate the effect of various factors on the optical transmission through capillary-array windows. These factors included pore diameter, window thickness, open area ratio (OAR), exposed area, wavelength of incident radiation, and incident angle of radiation. Subsequent statistical analyses, including effect analysis, ANOVA, and regression analysis, were conducted to determine the optimal optical transmission through microporous and milliporous capillary-array windows. The results showed that the optimal optical transmission through microporous capillary-array windows was 59.24%, which closely aligned with the theoretical maximum of 60%. Similarly, the optimal optical transmission through milliporous capillary-array windows was found to be 45.03%, which aligned well with the theoretical maximum of 44%.In addition to the optical transmission measurements, several rounds of pressure tests were conducted on the capillary-array windows to evaluate their mechanical durability. The windows were subjected to two initial pressure differentials: (1) 10^(-6) torr to 20 mtorr, which mimics the condition of optical transmission measurements through the capillary-array windows in the Electron Cyclotron Resonance (ECR) plasma system, and (2) 20 mtorr to 760 torr, which is the pressure range required for generating UV and VUV radiation. All capillary-array windows were observed to withstand these pressure differentials without any failure. Further pressure tests were conducted to investigate the maximum pressure differential that capillary-array windows could withstand before failure. The results revealed that the capillary-array windows demonstrated a high tolerance for pressure differentials of several hundred of psi without experiencing any failure.
The explosive growth of next-generation sequencing (NGS) read datasets drives a need for new faster read mappers. One class of read mappers, called all-mappers, is designed to identify all mapping ...locations of each read. Many all-mappers have been developed over the past few years, but they are either time-consuming or memory-consuming. Here, we present BitMapper2, a GPU-accelerated read mapper that reports all mapping locations of NGS reads. To make full use of the parallel processing capability of GPUs, BitMapper2 proposes the sparse q-gram index, which reduces the memory requirement and the data transfer time between GPU and CPU. We also design the filtration part and the verification part of BitMapper2 specifically for the architecture of GPU. In addition, BitMapper2 is still time-efficient and memory-efficient even if there is no GPU available. Experiments show that BitMapper2 was significantly faster than the state-of-the-art all-mappers, while requiring less space.
In this paper, a missile terminal guidance law based on a new Deep Deterministic Policy Gradient (DDPG) algorithm is proposed to intercept a maneuvering target equipped with an infrared decoy. First, ...to deal with the issue that the missile cannot accurately distinguish the target from the decoy, the energy center method is employed to obtain the equivalent energy center (called virtual target) of the target and decoy, and the model for the missile and the virtual decoy is established. Then, an improved DDPG algorithm is proposed based on a trusted-search strategy, which significantly increases the train efficiency of the previous DDPG algorithm. Furthermore, combining the established model, the network obtained by the improved DDPG algorithm and the reward function, an intelligent missile terminal guidance scheme is proposed. Specifically, a heuristic reward function is designed for training and learning in combat scenarios. Finally, the effectiveness and robustness of the proposed guidance law are verified by Monte Carlo tests, and the simulation results obtained by the proposed scheme and other methods are compared to further demonstrate its superior performance.
•A novel double drug electrospun nanofiber dressing with antibacterial, antioxidant, inflammation inhibition, and wound healing.•Pionin plays a key role in blocking the growth of MRSA and E. ...coli.•GHK-Cu decreased the ROS level and promoted M1 to M2 macrophage phenotype switching.•Drug nanofibers significantly reduced the inflammatory response through antioxidant effects and enhanced epidermal regeneration and collagen deposition.
Biocompatible, antibacterial, anti-inflammatory, and tissue regenerative smart dressings are in urgent need for infected skin wound repair in clinics. Portable in situ 3D-electrospun technology has the great advantage of direct deposition of required smart dressing on wound surfaces. Here, we fabricated a copper peptide (GHK-Cu) and quaternium-73 (Pionin) dual-drug-loaded polyvinyl butyral (PVB)/polyvinylpyrrolidone (PVP) smart nanofibers dressing using in-situ electrospinning technology for skin wound repair. The physicochemical properties and biological activities of smart dressing were extensively analyzed. In vivo biocompatibility, anti-oxidant, anti-inflammatory, and antimicrobial activities of smart dressing were analyzed during wound healing. Stable and homogeneous PVB/PVP nanofiber smart dressing with uniformly distributed GHK-Cu and Pionin and anabolic biological activities was obtained. Biocompatible smart dressing gave a sustained release of GHK-Cu and Pionin, promoted the migration and adhesion of dermal fibroblasts and keratinocytes, and showed anti-oxidant and anti-apoptotic effects in vitro and in vivo. Smart dressing exerted anti-inflammatory properties via M1 to M2 macrophage phenotype switching and effectively promoted wound healing. Pionin released from smart dressing not only killed but also inhibited the expression and delivery of virulence factor expression and bacteria adhesion. During wound healing, smart dressing promoted the proliferation of cells in the epidermal tissue, epithelial tissue remodeling, granulation tissue growth, neovascularization, and M2 macrophage polarization. Moreover, this smart dressing scavenged excess reactive oxygen species, increased SOD3 and SIRT1 expression, and repaired peroxidized tissue, consequently promoting wound healing. In summary, our results indicate that GHK-Cu/Pionin-loaded in situ electrospun PVB/PVP smart dressing promotes wound healing via anti-oxidant, anti-inflammatory, antimicrobial, and tissue regenerative effects, suggesting clinical application of this smart dressing for complicated skin wound healing.
A draft human pangenome reference Liao, Wen-Wei; Asri, Mobin; Ebler, Jana ...
Nature (London),
05/2023, Volume:
617, Issue:
7960
Journal Article
Peer reviewed
Open access
Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse ...individuals
. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample.
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