uShuffle: A useful tool for shuffling biological sequences while preserving the k-let counts

Abstract We present a bioinformatics tool (named uShuffle) for generating uniform random permutations of biological sequences (such as DNAs, RNAs, and proteins) that preserve the exact k-let counts. The uShuffle program is based on the Euler algorithm and uses Wilson’s algorithm in the crucial step of arborescence generation. Our implementation of these algorithms is carefully engineered; it is shown by our experiments to be both extremely efficient and very scalable. By allowing arbitrary alphabet size and let size, the uShuffle program is also far superior to the existing tools in terms of versatility. For the convenience of the users, we provide the uShuffle program in a variety of programming languages: C, Java, C#, Perl, and Python. The websit

Predicting RNA Secondary Structures By Folding Simulation: Software and Experiments

We present a new method for predicting the secondary structure of RNA sequences. Using our method, each RNA nucleotide of an RNA Sequence is represented as a point on a 3D triangular lattice. Using the Simulated Annealing technique, we manipulate the location of the points on the lattice. We explore various scoring functions for judging the relative quality of the structures created by these manipulations. After near optimal configurations on the lattice have been found, we describe how the lattice locations of the nucleotides can be used to predict a secondary structure for the sequence. This prediction can be further improved by using a greedy, 2-interval post-processing step to find the maximum independent set of the helices predicted by the lattice. The complete method, DeltaIS, is then compared with HotKnot, a popular secondary structure prediction program. We evaluate the relative effectiveness of DeltaIS and HotKnot by predicting 252 sequences from the Pseudobase Database. The predictions of each method are then scored against the true structures. We show DeltaIS to be superior to HotKnot for shorter RNA sequences, and in the number of perfectly predicted structures

White-nose Syndrome at Mammoth Cave National Park: Actions Before and After Its Detection

Since it was identified in the United States in 2006, white-nose syndrome (WNS) in bats has become an important issue in the management of caves and bats at Mammoth Cave National Park (MACA). The threat of its arrival has led to more intense monitoring of bat populations, increased studies, and interventions with both the visiting public and researchers. The timeline of MACA’s WNS response is shown in Table 1

The Tetragnatha kauaiensis genome sheds light on the origins of genomic novelty in spider

Spiders (Araneae) have a diverse spectrum of morphologies, behaviors, and physiologies. Attempts to understand the genomic-basis of this diversity are often hindered by their large, heterozygous, and AT-rich genomes with high repeat content resulting in highly fragmented, poor-quality assemblies. As a result, the key attributes of spider genomes, including gene family evolution, repeat content, and gene function, remain poorly understood. Here, we used Illumina and Dovetail Chicago technologies to sequence the genome of the long-jawed spider Tetragnatha kauaiensis, producing an assembly distributed along 3,925 scaffolds with an N50 of ∼2 Mb. Using comparative genomics tools, we explore genome evolution across available spider assemblies. Our findings suggest that the previously reported and vast genome size variation in spiders is linked to the different representation and number of transposable elements. Using statistical tools to uncover gene-family level evolution, we find expansions associated with the sensory perception of taste, immunity, and metabolism. In addition, we report strikingly different histories of chemosensory, venom, and silk gene families, with the first two evolving much earlier, affected by the ancestral whole genome duplication in Arachnopulmonata (∼450 Ma) and exhibiting higher numbers. Together, our findings reveal that spider genomes are highly variable and that genomic novelty may have been driven by the burst of an ancient whole genome duplication, followed by gene family and transposable element expansion

Evaluation of the diagnostic performance of the urine dipstick test for the detection of urinary tract infections in patients treated in Kenyan hospitals

This work is a subset of the large HATUA (Holistic approach to unravel antibacterial resistance) consortium funded by the UK Medical Research Council (MR/S004785/1).Introduction. Culture is the gold-standard diagnosis for urinary tract infections (UTIs). However, most hospitals in low-resource countries lack adequately equipped laboratories and relevant expertise to perform culture and, therefore, rely heavily on dipstick tests for UTI diagnosis. Research gap. In many Kenyan hospitals, routine evaluations are rarely done to assess the accuracy of popular screening tests such as the dipstick test. As such, there is a substantial risk of misdiagnosis emanating from inaccuracy in proxy screening tests. This may result in misuse, under-use or over-use of antimicrobials. Aim. The present study aimed to assess the accuracy of the urine dipstick test as a proxy for the diagnosis of UTIs in selected Kenyan hospitals. Methods. A hospital-based cross-sectional method was used. The utility of dipstick in the diagnosis of UTIs was assessed using midstream urine against culture as the gold standard. Results. The dipstick test predicted 1416 positive UTIs, but only 1027 were confirmed positive by culture, translating to a prevalence of 54.1 %. The sensitivity of the dipstick test was better when leucocytes and nitrite tests were combined (63.1 %) than when the two tests were separate (62.6 and 50.7 %, respectively). Similarly, the two tests combined had a better positive predictive value (87.0 %) than either test alone. The nitrite test had the best specificity (89.8 %) and negative predictive value (97.4 %) than leucocytes esterase (L.E) or both tests combined. In addition, sensitivity in samples from inpatients (69.2 %) was higher than from outpatients (62.7 %). Furthermore, the dipstick test had a better sensitivity and positive predictive value among female (66.0 and 88.6 %) than male patients (44.3 and 73.9 %). Among the various patient age groups, the dipstick test’s sensitivity and positive predictive value were exceptionally high in patients ≥75 years old (87.5 and 93.3 %). Conclusion. Discrepancies in prevalence from the urine dipstick test and culture, the gold standard, indicate dipstick test inadequacy for accurate UTI diagnosis. The finding also demonstrates the need for urine culture for accurate UTI diagnosis. However, considering it is not always possible to perform a culture, especially in low-resource settings, future studies are needed to combine specific UTI symptoms and dipstick results to assess possible increases in the test’s sensitivity. There is also a need to develop readily available and affordable algorithms that can detect UTIs where culture is not available.Publisher PDFPeer reviewe

Infection of mouse macrophages by seasonal influenza viruses can be restricted at the level of virus entry and at a late stage in the virus life cycle

Airway epithelial cells are susceptible to infection with seasonal influenza A viruses (IAV), resulting in productive virus replication and release. Macrophages (MΦ) are also permissive to IAV infection; however, virus replication is abortive. Currently, it is unclear how productive infection of MΦ is impaired or the extent to which seasonal IAV replicate in MΦ. Herein, we compared mouse MΦ and epithelial cells for their ability to support genomic replication and transcription, synthesis of viral proteins, assembly of virions, and release of infectious progeny following exposure to genetically defined IAV. We confirm that seasonal IAV differ in their ability to utilize cell surface receptors for infectious entry and that this represents one level of virus restriction. Following virus entry, we demonstrate synthesis of all eight segments of genomic viral RNA (vRNA) and mRNA, as well as seven distinct IAV proteins, in IAV-infected mouse MΦ. Although newly synthesized hemagglutinin (HA) and neuraminidase (NA) glycoproteins are incorporated into the plasma membrane and expressed at the cell surface, electron microscopy confirmed that virus assembly was defective in IAV-infected MΦ, defining a second level of restriction late in the virus life cycle

Close Galaxy Pairs at z = 3: A Challenge to UV Luminosity Abundance Matching

We use a sample of z~3 Lyman Break Galaxies (LBGs) to examine close pair clustering statistics in comparison to LCDM-based models of structure formation. Samples are selected by matching the LBG number density and by matching the observed LBG 3-D correlation function of LBGs over the two-halo term region. We show that UV-luminosity abundance matching cannot reproduce the observed data, but if subhalos are chosen to reproduce the observed clustering of LBGs we are able to reproduce the observed LBG pair fraction, (Nc), defined as the average number of companions per galaxy. This model suggests an over abundance of LBGs by a factor of ~5 over those observed, suggesting that only 1 in 5 halos above a fixed mass hosts a galaxy with LBG-like UV luminosity detectable via LBG selection techniques. We find a total observable close pair fraction of 23 \pm 0.6% (17.7 \pm 0.5%) using a prototypical cylinder radius in our overdense fiducial model and 8.3 \pm 0.5% (5.6 \pm 0.2%) in an abundance matched model (impurity corrected). For the matched spectroscopic slit analysis, we find Ncs = 5.1\pm0.2% (1.68\pm0.02%), the average number of companions observed serendipitously in our for fiducial slits (abundance matched), whereas the observed fraction of serendipitous spectroscopic close pairs is 4.7\pm1.5 per cent using the full LBG sample and 7.1\pm2.3% for a subsample with higher signal-to-noise ratio. We show that the standard method of halo assignment fails to reproduce the break in the LBG close pair behavior at small scale. To reconcile these discrepancies we suggest that a plausible fraction of LBGs in close pairs with lower mass than our sample experience interaction-induced enhanced star formation that boosts their luminosity sufficiently to be detected in observational sample but are not included in the abundance matched simulation sample.Comment: 18 pages, 12 figures, 1 table, published in MNRA

Predominance of multidrug-resistant bacteria causing urinary tract infections among symptomatic patients in East Africa : a call for action

Background In low- and middle-income countries, antibiotics are often prescribed for patients with symptoms of urinary tract infections (UTIs) without microbiological confirmation. Inappropriate antibiotic use can contribute to antimicrobial resistance (AMR) and the selection of MDR bacteria. Data on antibiotic susceptibility of cultured bacteria are important in drafting empirical treatment guidelines and monitoring resistance trends, which can prevent the spread of AMR. In East Africa, antibiotic susceptibility data are sparse. To fill the gap, this study reports common microorganisms and their susceptibility patterns isolated from patients with UTI-like symptoms in Kenya, Tanzania and Uganda. Within each country, patients were recruited from three sites that were sociodemographically distinct and representative of different populations. Methods UTI was defined by the presence of >104 cfu/mL of one or two uropathogens in mid-stream urine samples. Identification of microorganisms was done using biochemical methods. Antimicrobial susceptibility testing was performed by the Kirby–Bauer disc diffusion assay. MDR bacteria were defined as isolates resistant to at least one agent in three or more classes of antimicrobial agents. Results Microbiologically confirmed UTI was observed in 2653 (35.0%) of the 7583 patients studied. The predominant bacteria were Escherichia coli (37.0%), Staphylococcus spp. (26.3%), Klebsiella spp. (5.8%) and Enterococcus spp. (5.5%). E. coli contributed 982 of the isolates, with an MDR proportion of 52.2%. Staphylococcus spp. contributed 697 of the isolates, with an MDR rate of 60.3%. The overall proportion of MDR bacteria (n = 1153) was 50.9%. Conclusions MDR bacteria are common causes of UTI in patients attending healthcare centres in East African countries, which emphasizes the need for investment in laboratory culture capacity and diagnostic algorithms to improve accuracy of diagnosis that will lead to appropriate antibiotic use to prevent and control AMR.Peer reviewe