A proteogenomic update to Yersinia: enhancing genome annotation

<p>Abstract</p> <p>Background</p> <p>Modern biomedical research depends on a complete and accurate proteome. With the widespread adoption of new sequencing technologies, genome sequences are generated at a near exponential rate, diminishing the time and effort that can be invested in genome annotation. The resulting gene set contains numerous errors in even the most basic form of annotation: the primary structure of the proteins.</p> <p>Results</p> <p>The application of experimental proteomics data to genome annotation, called proteogenomics, can quickly and efficiently discover misannotations, yielding a more accurate and complete genome annotation. We present a comprehensive proteogenomic analysis of the plague bacterium, <it>Yersinia pestis KIM</it>. We discover non-annotated genes, correct protein boundaries, remove spuriously annotated ORFs, and make major advances towards accurate identification of signal peptides. Finally, we apply our data to 21 other <it>Yersinia </it>genomes, correcting and enhancing their annotations.</p> <p>Conclusions</p> <p>In total, 141 gene models were altered and have been updated in RefSeq and Genbank, which can be accessed seamlessly through any NCBI tool (e.g. blast) or downloaded directly. Along with the improved gene models we discover new, more accurate means of identifying signal peptides in proteomics data.</p

Data-Driven Process Discovery - Revealing Conditional Infrequent Behavior from Event Logs

Process discovery methods automatically infer process models from event logs. Often, event logs contain so-called noise, e.g., infrequent outliers or recording errors, which obscure the main behavior of the process. Existing methods filter this noise based on the frequency of event labels: infrequent paths and activities are excluded. However, infrequent behavior may reveal important insights into the process. Thus, not all infrequent behavior should be considered as noise. This paper proposes the Data-aware Heuristic Miner (DHM), a process discovery method that uses the data attributes to distinguish infrequent paths from random noise by using classification techniques. Data- and control-flow of the process are discovered together. We show that the DHM is, to some degree, robust against random noise and reveals data-driven decisions, which are filtered by other discovery methods. The DHM has been successfully tested on several real-life event logs, two of which we present in this paper

Efficient Process Model Discovery Using Maximal Pattern Mining

In recent years, process mining has become one of the most important and promising areas of research in the field of business process management as it helps businesses understand, analyze, and improve their business processes. In particular, several proposed techniques and algorithms have been proposed to discover and construct process models from workflow execution logs (i.e., event logs). With the existing techniques, mined models can be built based on analyzing the relationship between any two events seen in event logs. Being restricted by that, they can only handle special cases of routing constructs and often produce unsound models that do not cover all of the traces seen in the log. In this paper, we propose a novel technique for process discovery using Maximal Pattern Mining (MPM) where we construct patterns based on the whole sequence of events seen on the traces—ensuring the soundness of the mined models. Our MPM technique can handle loops (of any length), duplicate tasks, non-free choice constructs, and long distance dependencies. Our evaluation shows that it consistently achieves better precision, replay fitness and efficiency than the existing techniques

Interactive Data-Driven Process Model Construction

\u3cp\u3eProcess discovery algorithms address the problem of learning process models from event logs. Typically, in such settings a user’s activity is limited to configuring the parameters of the discovery algorithm, and hence the user expertise/domain knowledge can not be incorporated during traditional process discovery. In a setting where the event logs are noisy, incomplete and/or contain uninteresting activities, the process models discovered by discovery algorithms are often inaccurate and/or incomprehensible. Furthermore, many of these automated techniques can produce unsound models and/or cannot discover duplicate activities, silent activities etc. To overcome such shortcomings, we introduce a new concept to interactively discover a process model, by combining a user’s domain knowledge with the information from the event log. The discovered models are always sound and can have duplicate activities, silent activities etc. An objective evaluation and a case study shows that the proposed approach can outperform traditional discovery techniques.\u3c/p\u3

Integrated next-generation sequencing of 16S rDNA and metaproteomics differentiate the healthy urine microbiome from asymptomatic bacteriuria in neuropathic bladder associated with spinal cord injury

<p>Abstract</p> <p>Background</p> <p>Clinical dogma is that healthy urine is sterile and the presence of bacteria with an inflammatory response is indicative of urinary tract infection (UTI). Asymptomatic bacteriuria (ABU) represents the state in which bacteria are present but the inflammatory response is negligible. Differentiating ABU from UTI is diagnostically challenging, but critical because overtreatment of ABU can perpetuate antimicrobial resistance while undertreatment of UTI can result in increased morbidity and mortality. In this study, we describe key characteristics of the healthy and ABU urine microbiomes utilizing 16S rRNA gene (16S rDNA) sequencing and metaproteomics, with the future goal of utilizing this information to personalize the treatment of UTI based on key individual characteristics.</p> <p>Methods</p> <p>A cross-sectional study of 26 healthy controls and 27 healthy subjects at risk for ABU due to spinal cord injury-related neuropathic bladder (NB) was conducted. Of the 27 subjects with NB, 8 voided normally, 8 utilized intermittent catheterization, and 11 utilized indwelling Foley urethral catheterization for bladder drainage. Urine was obtained by clean catch in voiders, or directly from the catheter in subjects utilizing catheters. Urinalysis, urine culture and 16S rDNA sequencing were performed on all samples, with metaproteomic analysis performed on a subsample.</p> <p>Results</p> <p>A total of 589454 quality-filtered 16S rDNA sequence reads were processed through a NextGen 16S rDNA analysis pipeline. Urine microbiomes differ by normal bladder function vs. NB, gender, type of bladder catheter utilized, and duration of NB. The top ten bacterial taxa showing the most relative abundance and change among samples were Lactobacillales, Enterobacteriales, Actinomycetales, Bacillales, Clostridiales, Bacteroidales, Burkholderiales, Pseudomonadales, Bifidobacteriales and Coriobacteriales. Metaproteomics confirmed the 16S rDNA results, and functional human protein-pathogen interactions were noted in subjects where host defenses were initiated.</p> <p>Conclusions</p> <p>Counter to clinical belief, healthy urine is not sterile. The healthy urine microbiome is characterized by a preponderance of <it>Lactobacillales</it> in women and <it>Corynebacterium</it> in men. The presence and duration of NB and method of urinary catheterization alter the healthy urine microbiome. An integrated approach of 16S rDNA sequencing with metaproteomics improves our understanding of healthy urine and facilitates a more personalized approach to prevention and treatment of infection.</p