RepeatFS: a file system providing reproducibility through provenance and automation.

MOTIVATION: Reproducibility is of central importance to the scientific process. The difficulty of consistently replicating and verifying experimental results is magnified in the era of big data, in which bioinformatics analysis often involves complex multi-application pipelines operating on terabytes of data. These processes result in thousands of possible permutations of data preparation steps, software versions and command-line arguments. Existing reproducibility frameworks are cumbersome and involve redesigning computational methods. To address these issues, we developed RepeatFS, a file system that records, replicates and verifies informatics workflows with no alteration to the original methods. RepeatFS also provides several other features to help promote analytical transparency and reproducibility, including provenance visualization and task automation. RESULTS: We used RepeatFS to successfully visualize and replicate a variety of bioinformatics tasks consisting of over a million operations with no alteration to the original methods. RepeatFS correctly identified all software inconsistencies that resulted in replication differences. AVAILABILITYAND IMPLEMENTATION: RepeatFS is implemented in Python 3. Its source code and documentation are available at https://github.com/ToniWestbrook/repeatfs. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Improving resource utilisation and outcomes after total knee arthroplasty through technology-enabled patient engagement.

BACKGROUND: A multi-modal, technology-enabled, patient engagement and pathway management solution (PES) for patients undergoing primary total knee arthroplasty (TKA) was evaluated. The primary outcome measure was length of stay (LoS). The secondary outcome measures were clinical and patient-reported outcomes (PROMs). METHODS: Retrospective analysis of a consecutive series of 1256 TKA patients before (n = 783) and after (n = 473) implementation of the PES. LoS, PROMs, complications, readmissions, and return to theatre were measured. Results were analysed using bivariate and multivariable regression using general linear models, and a sensitivity analysis on LoS was conducted using interrupted time series (ITS) methods. RESULTS: Patients in the PES cohort had a significantly shorter mean LoS of two days (mean 4.7 days) versus the Pre-PES patients (mean 6.7 days; p < 0.001) in multivariate analysis. PES was also associated with a significant reduction in rates of reoperation within 60 days compared with Pre-PES (adjusted rate 2.2% versus 5.0%, p = 0.031). There were no statistically significant differences in the 60-day complication rate and 30-day readmission rate. All PROMs in the PES cohort demonstrated significant improvement (change from baseline to six months postoperative) compared with Pre-PES (Oxford Knee Score, 20.1 versus 15.5, p < 0.001; EQ-5D Index, 0.40 versus 0.32, p = 0.005; and EQ VAS, 22.9 versus 8.3, p < 0.001). CONCLUSIONS: Outcomes following TKA performed in enhanced recovery programs may be improved using technology to more effectively engage patients and streamline their surgical pathway. Integration of such solutions may significantly reduce LoS and improve PROMs without negatively impacting clinical outcomes.

Comparative Genomics of Pathogenic and Nonpathogenic Beetle-Vectored Fungi in the Genus Geosmithia.

Geosmithia morbida is an emerging fungal pathogen which serves as a model for examining the evolutionary processes behind pathogenicity because it is one of two known pathogens within a genus of mostly saprophytic, beetle-associated, fungi. This pathogen causes thousand cankers disease in black walnut trees and is vectored into the host via the walnut twig beetle. Geosmithia morbida was first detected in western United States and currently threatens the timber industry concentrated in eastern United States. We sequenced the genomes of G. morbida in a previous study and two nonpathogenic Geosmithia species in this work and compared these species to other fungal pathogens and nonpathogens to identify genes under positive selection in G. morbida that may be associated with pathogenicity. Geosmithia morbida possesses one of the smallest genomes among the fungal species observed in this study, and one of the smallest fungal pathogen genomes to date. The enzymatic profile in this pathogen is very similar to its nonpathogenic relatives. Our findings indicate that genome reduction or retention of a smaller genome may be an important adaptative force during the evolution of a specialized lifestyle in fungal species that occupy a specificniche, such as beetle vectored tree pathogens. We also present potential genes under selection in G. morbida that could be important for adaptation to a pathogenic lifestyle.

PALADIN: protein alignment for functional profiling whole metagenome shotgun data.

MOTIVATION: Whole metagenome shotgun sequencing is a powerful approach for assaying the functional potential of microbial communities. We currently lack tools that efficiently and accurately align DNA reads against protein references, the technique necessary for constructing a functional profile. Here, we present PALADIN-a novel modification of the Burrows-Wheeler Aligner that provides accurate alignment, robust reporting capabilities and orders-of-magnitude improved efficiency by directly mapping in protein space. RESULTS: We compared the accuracy and efficiency of PALADIN against existing tools that employ nucleotide or protein alignment algorithms. Using simulated reads, PALADIN consistently outperformed the popular DNA read mappers BWA and NovoAlign in detected proteins, percentage of reads mapped and ontological similarity. We also compared PALADIN against four existing protein alignment tools: BLASTX, RAPSearch2, DIAMOND and Lambda, using empirically obtained reads. PALADIN yielded results seven times faster than the best performing alternative, DIAMOND and nearly 8000 times faster than BLASTX. PALADIN's accuracy was comparable to all tested solutions. AVAILABILITY AND IMPLEMENTATION: PALADIN was implemented in C, and its source code and documentation are available at https://github.com/twestbrookunh/paladin. CONTACT: anthonyw@wildcats.unh.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

De novo genome assembly of Geosmithia morbida, the causal agent of thousand cankers disease.

Geosmithia morbida is a filamentous ascomycete that causes thousand cankers disease in the eastern black walnut tree. This pathogen is commonly found in the western U.S.; however, recently the disease was also detected in several eastern states where the black walnut lumber industry is concentrated. G. morbida is one of two known phytopathogens within the genus Geosmithia, and it is vectored into the host tree via the walnut twig beetle. We present the first de novo draft genome of G. morbida. It is 26.5 Mbp in length and contains less than 1% repetitive elements. The genome possesses an estimated 6,273 genes, 277 of which are predicted to encode proteins with unknown functions. Approximately 31.5% of the proteins in G. morbida are homologous to proteins involved in pathogenicity, and 5.6% of the proteins contain signal peptides that indicate these proteins are secreted. Several studies have investigated the evolution of pathogenicity in pathogens of agricultural crops; forest fungal pathogens are often neglected because research efforts are focused on food crops. G. morbida is one of the few tree phytopathogens to be sequenced, assembled and annotated. The first draft genome of G. morbida serves as a valuable tool for comprehending the underlying molecular and evolutionary mechanisms behind pathogenesis within the Geosmithia genus.

The mannequin sign.

STUDY DESIGN: Prospective observational study. OBJECTIVES: The critical appraisal of the mannequin sign in the validation of patients with symptoms of sciatica. SUMMARY OF BACKGROUND DATA: Sixty-five consecutive patients with magnetic resonance imaging-proven lumbar disc herniation and symptoms of sciatica. Mean patient age was 48 (range 28-62) years. Thirty-seven patients were male and 28 were female. METHODS: The mannequin sign is positive when a patient adopts an antalgic posture with the relevant lower limb flexed at the hip and knee with the pelvis tilting towards the affected side, in the classic manner of a mannequin's pose. Reproducibility of the sign was recorded when all patients were examined by a second clinician. Lumbar disc herniation with nerve root impingement was confirmed by magnetic resonance imaging. RESULTS: The mannequin sign had 100% reproducibility and 80% sensitivity in diagnosing lumbar disc herniations with nerve root impingement. Twenty-four patients had L4-L5 disc herniations and 41 had L5-S1 disc herniations. CONCLUSION: Astute clinical examination can minimize inaccurate diagnosis, unnecessary investigations, and even inappropriate surgical intervention. The mannequin sign, first observed and anecdotally reported by the senior author (D.C.), has now been critically appraised.