High throughput profile-profile based fold recognition for the entire human proteome

BACKGROUND: In order to maintain the most comprehensive structural annotation databases we must carry out regular updates for each proteome using the latest profile-profile fold recognition methods. The ability to carry out these updates on demand is necessary to keep pace with the regular updates of sequence and structure databases. Providing the highest quality structural models requires the most intensive profile-profile fold recognition methods running with the very latest available sequence databases and fold libraries. However, running these methods on such a regular basis for every sequenced proteome requires large amounts of processing power. In this paper we describe and benchmark the JYDE (Job Yield Distribution Environment) system, which is a meta-scheduler designed to work above cluster schedulers, such as Sun Grid Engine (SGE) or Condor. We demonstrate the ability of JYDE to distribute the load of genomic-scale fold recognition across multiple independent Grid domains. We use the most recent profile-profile version of our mGenTHREADER software in order to annotate the latest version of the Human proteome against the latest sequence and structure databases in as short a time as possible. RESULTS: We show that our JYDE system is able to scale to large numbers of intensive fold recognition jobs running across several independent computer clusters. Using our JYDE system we have been able to annotate 99.9% of the protein sequences within the Human proteome in less than 24 hours, by harnessing over 500 CPUs from 3 independent Grid domains. CONCLUSION: This study clearly demonstrates the feasibility of carrying out on demand high quality structural annotations for the proteomes of major eukaryotic organisms. Specifically, we have shown that it is now possible to provide complete regular updates of profile-profile based fold recognition models for entire eukaryotic proteomes, through the use of Grid middleware such as JYDE

The Effect of Graft Selection on Patients’ Subjective Readiness to Return to Sport After ACL Reconstruction

Background: Patients who undergo ACL reconstruction with allografts may have an easier functional recovery compared to autograft patients. This is due to decreased donor site morbidity and less muscle atrophy compared to autograft patients. This “easier” recovery may be perceived by patients and may result in a subjective earlier readiness for return to sports. Hypothesis/Purpose: To determine if there is a difference in perceived readiness to return to sport (RTS) in the first year postoperative period between individuals who undergo ACL reconstruction utilizing bone-patellar tendon-bone (BTB) autografts or allografts. Study Design: Prospective Cohort Study, Level II Methods: This was a prospective, observational cohort study for patients aged 14-25 years old undergoing primary ACL reconstruction done either with BTB autograft or allograft. Patients completed questionnaires postoperatively evaluating their perceived ability to perform various activities, and their responses were used to compare subjective ability to RTS. Results: Fifty-nine patients were included in the study. Sixteen patients underwent ACL reconstruction with allograft while 43 patients received autograft. At 3 months those who received autograft reported higher perceived ability to cut (P = .003). At 6-months, patients who received allograft reconstruction reported higher perceived ability to run (P = .033), cut (P = .048), and decelerate (P = .008) as well as a higher overall perceived ability to RTS (P = .032). At all other times, there was no significant difference between cohorts’ subjective readiness to perform activities. Conclusion The results of this study indicate that at times within the first year of recovery following ACL reconstruction, patients who receive allografts and autografts may have significantly different perceived ability to perform activities or RTS. However, while present at various times throughout the first year of recovery, any difference in perceived ability to perform activities or in overall RTS is no longer present at 12 months. This study does not implicate a subjective difference in ability to return to sport or ability to perform sport-like activities between autograft or allograft as being associated with an increased risk for re-injury in the first year following surgery. Key Terms: knee ligament, ACL, allograft, imaging, general sports traum

Protein structure prediction servers at University College London

A number of state-of-the-art protein structure prediction servers have been developed by researchers working in the Bioinformatics Unit at University College London. The popular PSIPRED server allows users to perform secondary structure prediction, transmembrane topology prediction and protein fold recognition. More recent servers include DISOPRED for the prediction of protein dynamic disorder and DomPred for domain boundary prediction. These servers are available from our software home page at

Dense geographic and genomic sampling reveals paraphyly and a cryptic lineage in a classic sibling species complex

Incomplete or geographically biased sampling poses significant problems for research in phylogeography, population genetics, phylogenetics, and species delimitation. Despite the power of using genome-wide genetic markers in systematics and related fields, approaches such as the multispecies coalescent remain unable to easily account for unsampled lineages. The Empidonax difficilis/Empidonax occidentalis complex of small tyrannid flycatchers (Aves: Tyrannidae) is a classic example of widely distributed species with limited phenotypic geographic variation that was broken into two largely cryptic (or "sibling") lineages following extensive study. Though the group is well-characterized north of the US Mexico border, the evolutionary distinctiveness and phylogenetic relationships of southern populations remain obscure. In this article, we use dense genomic and geographic sampling across the majority of the range of the E. difficilis/E. occidentalis complex to assess whether current taxonomy and species limits reflect underlying evolutionary patterns, or whether they are an artifact of historically biased or incomplete sampling. We find that additional samples from Mexico render the widely recognized species-level lineage E. occidentalis paraphyletic, though it retains support in the best-fit species delimitation model from clustering analyses. We further identify a highly divergent unrecognized lineage in a previously unsampled portion of the group's range, which a cline analysis suggests is more reproductively isolated than the currently recognized species E. difficilis and E. occidentalis. Our phylogeny supports a southern origin of these taxa. Our results highlight the pervasive impacts of biased geographic sampling, even in well-studied vertebrate groups like birds, and illustrate what is a common problem when attempting to define species in the face of recent divergence and reticulate evolution

Kepler Exoplanet Candidate Host Stars are Preferentially Metal Rich

We find that Kepler exoplanet candidate (EC) host stars are preferentially metal-rich, including the low-mass stellar hosts of small-radius ECs. The last observation confirms a tentative hint that there is a correlation between the metallicity of low-mass stars and the presence of low-mass and small-radius exoplanets. In particular, we compare the J-H--g-r color-color distribution of Kepler EC host stars with a control sample of dwarf stars selected from the ~150,000 stars observed during Q1 and Q2 of the Kepler mission but with no detected planets. We find that at J-H = 0.30 characteristic of solar-type stars, the average g-r color of stars that host giant ECs is 4-sigma redder than the average color of the stars in the control sample. At the same time, the average g-r color of solar-type stars that host small-radius ECs is indistinguishable from the average color of the stars in the control sample. In addition, we find that at J-H = 0.62 indicative of late K dwarfs, the average g-r color of stars that host small-radius ECs is 4-sigma redder than the average color of the stars in the control sample. These offsets are unlikely to be caused by differential reddening, age differences between the two populations, or the presence of giant stars in the control sample. Stellar models suggest that the first color offset is due to a 0.2 dex enhancement in [Fe/H] of the giant EC host population at M_star = 1 M_Sun, while Sloan photometry of M 67 and NGC 6791 suggests that the second color offset is due to a similar [Fe/H] enhancement of the small-radius EC host population at M_star = 0.7 M_Sun. These correlations are a natural consequence of the core-accretion model of planet formation.Comment: 15 pages, 8 figures, and 1 table in emulateapj format; accepted for publication in Ap

TopNEXt: automatic DDA exclusion framework for multi-sample mass spectrometry experiments

Motivation: Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) experiments aim to produce high quality fragmentation spectra which can be used to annotate metabolites. However, current Data-Dependent Acquisition (DDA) approaches may fail to collect spectra of sufficient quality and quantity for experimental outcomes, and extend poorly across multiple samples by failing to share information across samples or by requiring manual expert input. Results: We present TopNEXt, a real-time scan prioritisation framework that improves data acquisition in multi-sample LC-MS/MS metabolomics experiments. TopNEXt extends traditional DDA exclusion methods across multiple samples by using a Region of Interest (RoI) and intensity-based scoring system. Through both simulated and lab experiments we show that methods incorporating these novel concepts acquire fragmentation spectra for an additional 10% of our set of target peaks and with an additional 20% of acquisition intensity. By increasing the quality and quantity of fragmentation spectra, TopNEXt can help improve metabolite identification with a potential impact across a variety of experimental contexts. Availability: TopNEXt is implemented as part of the ViMMS framework and the latest version can be found at https://github.com/glasgowcompbio/vimms. A stable version used to produce our results can be found at 10.5281/zenodo.7468914. Data can be found at 10.5525/gla.researchdata.1382

Planet Hunters: New Kepler planet candidates from analysis of quarter 2

We present new planet candidates identified in NASA Kepler quarter two public release data by volunteers engaged in the Planet Hunters citizen science project. The two candidates presented here survive checks for false-positives, including examination of the pixel offset to constrain the possibility of a background eclipsing binary. The orbital periods of the planet candidates are 97.46 days (KIC 4552729) and 284.03 (KIC 10005758) days and the modeled planet radii are 5.3 and 3.8 R_Earth. The latter star has an additional known planet candidate with a radius of 5.05 R_Earth and a period of 134.49 which was detected by the Kepler pipeline. The discovery of these candidates illustrates the value of massively distributed volunteer review of the Kepler database to recover candidates which were otherwise uncatalogued.Comment: Accepted to A

Exoplanet atmospheres Characterization Observatory payload short-wave infrared channel: EChO SWiR

EChO (Exoplanet atmospheres Characterization Observatory), a proposal for exoplanets exploration space mission, is considered the next step for planetary atmospheres characterization. It would be a dedicated observatory to uncover a large selected sample of planets spanning a wide range of masses (from gas giants to super-Earths) and orbital temperatures (from hot to habitable). All targets move around stars of spectral types F, G, K, and M. EChO would provide an unprecedented view of the atmospheres of planets in the solar neighbourhood. The consortium formed by various institutions of different countries proposed as ESA M3 an integrated spectrometer payload for EChO covering the wavelength interval 0.4 to 16 µm. This instrument is subdivided into 4 channels: a visible channel, which includes a fine guidance system (FGS) and a VIS spectrometer, a near infrared channel (SWiR), a middle infrared channel (MWiR), and a long wave infrared module (LWiR). In addition, it contains a common set of optics spectrally dividing the wavelength coverage and injecting the combined light of parent stars and their exoplanets into the different channels. The proposed payload meets all of the key performance requirements detailed in the ESA call for proposals as well as all scientific goals. EChO payload is based on different spectrometers covering the spectral range mentioned above. Among them, SWiR spectrometer would work from 2.45 microns to 5.45 microns. In this paper, the optical and mechanical designs of the SWiR channel instrument are reported on

Host-Microbe Co-metabolism Dictates Cancer Drug Efficacy in C. elegans

Fluoropyrimidines are the first-line treatment for colorectal cancer, but their efficacy is highly variable between patients. We queried whether gut microbes, a known source of inter-individual variability, impacted drug efficacy. Combining two tractable genetic models, the bacterium E. coli and the nematode C. elegans, we performed three-way high-throughput screens that unraveled the complexity underlying host-microbe-drug interactions. We report that microbes can bolster or suppress the effects of fluoropyrimidines through metabolic drug interconversion involving bacterial vitamin B-6, B-9, and ribonucleotide metabolism. Also, disturbances in bacterial deoxynucleotide pools amplify 5-FU-induced autophagy and cell death in host cells, an effect regulated by the nucleoside diphosphate kinase ndk-1. Our data suggest a two-way bacterial mediation of fluoropyrimidine effects on host metabolism, which contributes to drug efficacy. These findings highlight the potential therapeutic power of manipulating intestinal microbiota to ensure host metabolic health and treat disease.Peer reviewe