Evaluation of Trace Alignment Quality and its Application in Medical Process Mining

Trace alignment algorithms have been used in process mining for discovering the consensus treatment procedures and process deviations. Different alignment algorithms, however, may produce very different results. No widely-adopted method exists for evaluating the results of trace alignment. Existing reference-free evaluation methods cannot adequately and comprehensively assess the alignment quality. We analyzed and compared the existing evaluation methods, identifying their limitations, and introduced improvements in two reference-free evaluation methods. Our approach assesses the alignment result globally instead of locally, and therefore helps the algorithm to optimize overall alignment quality. We also introduced a novel metric to measure the alignment complexity, which can be used as a constraint on alignment algorithm optimization. We tested our evaluation methods on a trauma resuscitation dataset and provided the medical explanation of the activities and patterns identified as deviations using our proposed evaluation methods.Comment: 10 pages, 6 figures and 5 table

Process-oriented Iterative Multiple Alignment for Medical Process Mining

Adapted from biological sequence alignment, trace alignment is a process mining technique used to visualize and analyze workflow data. Any analysis done with this method, however, is affected by the alignment quality. The best existing trace alignment techniques use progressive guide-trees to heuristically approximate the optimal alignment in O(N2L2) time. These algorithms are heavily dependent on the selected guide-tree metric, often return sum-of-pairs-score-reducing errors that interfere with interpretation, and are computationally intensive for large datasets. To alleviate these issues, we propose process-oriented iterative multiple alignment (PIMA), which contains specialized optimizations to better handle workflow data. We demonstrate that PIMA is a flexible framework capable of achieving better sum-of-pairs score than existing trace alignment algorithms in only O(NL2) time. We applied PIMA to analyzing medical workflow data, showing how iterative alignment can better represent the data and facilitate the extraction of insights from data visualization.Comment: accepted at ICDMW 201

A summary of the 2012 JHU CLSP Workshop on Zero Resource Speech Technologies and Models of Early Language Acquisition

We summarize the accomplishments of a multi-disciplinary workshop exploring the computational and scientific issues surrounding zero resource (unsupervised) speech technologies and related models of early language acquisition. Centered around the tasks of phonetic and lexical discovery, we consider unified evaluation metrics, present two new approaches for improving speaker independence in the absence of supervision, and evaluate the application of Bayesian word segmentation algorithms to automatic subword unit tokenizations. Finally, we present two strategies for integrating zero resource techniques into supervised settings, demonstrating the potential of unsupervised methods to improve mainstream technologies.5 page(s

Development and Validation of Clinical Whole-Exome and Whole-Genome Sequencing for Detection of Germline Variants in Inherited Disease

Context.-With the decrease in the cost of sequencing, the clinical testing paradigm has shifted from single gene to gene panel and now whole-exome and whole-genome sequencing. Clinical laboratories are rapidly implementing next-generation sequencing-based whole-exome and whole-genome sequencing. Because a large number of targets are covered by whole-exome and whole-genome sequencing, it is critical that a laboratory perform appropriate validation studies, develop a quality assurance and quality control program, and participate in proficiency testing. Objective.-To provide recommendations for wholeexome and whole-genome sequencing assay design, validation, and implementation for the detection of germline variants associated in inherited disorders. Data Sources.-An example of trio sequencing, filtration and annotation of variants, and phenotypic consideration to arrive at clinical diagnosis is discussed. Conclusions.-It is critical that clinical laboratories planning to implement whole-exome and whole-genome sequencing design and validate the assay to specifications and ensure adequate performance prior to implementation. Test design specifications, including variant filtering and annotation, phenotypic consideration, guidance on consenting options, and reporting of incidental findings, are provided. These are important steps a laboratory must take to validate and implement whole-exome and whole-genome sequencing in a clinical setting for germline variants in inherited disorders

Development and Validation of Targeted Next-Generation Sequencing Panels for Detection of Germline Variants in Inherited Diseases.

Context.-The number of targeted next-generation sequencing (NGS) panels for genetic diseases offered by clinical laboratories is rapidly increasing. Before an NGS-based test is implemented in a clinical laboratory, appropriate validation studies are needed to determine the performance characteristics of the test. Objective.-To provide examples of assay design and validation of targeted NGS gene panels for the detection of germline variants associated with inherited disorders. Data Sources.-The approaches used by 2 clinical laboratories for the development and validation of targeted NGS gene panels are described. Important design and validation considerations are examined. Conclusions.-Clinical laboratories must validate performance specifications of each test prior to implementation. Test design specifications and validation data are provided, outlining important steps in validation of targeted NGS panels by clinical diagnostic laboratories

Spectroscopy of very hot plasma in non-flaring parts of a solar limb active region: spatial and temporal properties

In this work we investigate the thermal structure of an off-limb active region in various non-flaring areas, as it provides key information on the way these structures are heated. In particular, we concentrate in the very hot component (>3 MK) as it is a crucial element to discriminate between different heating mechanisms. We present an analysis using Fe and Ca emission lines from both SOHO/SUMER and HINODE/EIS. A dataset covering all ionization stages from Fe X to Fe XIX has been used for the thermal analysis (both DEM and EM). Ca XIV is used for the SUMER-EIS radiometric cross-calibration. We show how the very hot plasma is present and persistent almost everywhere in the core of the limb AR. The off-limb AR is clearly structured in Fe XVIII. Almost everywhere, the EM analysis reveals plasma at 10 MK (visible in Fe XIX emission) which is down to 0.1% of EM of the main 3 MK plasma. We estimate the power law index of the hot tail of the EM to be between -8.5 and -4.4. However, we leave an open question on the possible existence of a small minor peak at around 10 MK. The absence in some part of the AR of Fe XIX and Fe XXIII lines (which fall into our spectral range) enables us to determine an upper limit on the EM at such temperatures. Our results include a new Ca XIV 943.59 \AA~ atomic model

College of American Pathologists\u27 Laboratory Standards for Next-Generation Sequencing Clinical Tests

Context.-The higher throughput and lower per-base cost of next-generation sequencing (NGS) as compared to Sanger sequencing has led to its rapid adoption in clinical testing. The number of laboratories offering NGS-based tests has also grown considerably in the past few years, despite the fact that specific Clinical Laboratory Improvement Amendments of 1988/College of American Pathologists (CAP) laboratory standards had not yet been developed to regulate this technology. Objective.-To develop a checklist for clinical testing using NGS technology that sets standards for the analytic wet bench process and for bioinformatics or \u27\u27 dry bench\u27\u27 analyses. As NGS-based clinical tests are new to diagnostic testing and are of much greater complexity than traditional Sanger sequencing-based tests, there is an urgent need to develop new regulatory standards for laboratories offering these tests. Design.-To develop the necessary regulatory framework for NGS and to facilitate appropriate adoption of this technology for clinical testing, CAP formed a committee in 2011, the NGS Work Group, to deliberate upon the contents to be included in the checklist. Results.-A total of 18 laboratory accreditation checklist requirements for the analytic wet bench process and bioinformatics analysis processes have been included within CAP\u27s molecular pathology checklist (MOL). Conclusions.-This report describes the important issues considered by the CAP committee during the development of the new checklist requirements, which address documentation, validation, quality assurance, confirmatory testing, exception logs, monitoring of upgrades, variant interpretation and reporting, incidental findings, data storage, version traceability, and data transfer confidentiality

Enhanced mitochondrial genome analysis: bioinformatic and long-read sequencing advances and their diagnostic implications

Introduction: Primary mitochondrial diseases (PMDs) comprise a large and heterogeneous group of genetic diseases that result from pathogenic variants in either nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). Widespread adoption of next-generation sequencing (NGS) has improved the efficiency and accuracy of mtDNA diagnoses; however, several challenges remain. Areas covered: In this review, we briefly summarize the current state of the art in molecular diagnostics for mtDNA and consider the implications of improved whole genome sequencing (WGS), bioinformatic techniques, and the adoption of long-read sequencing, for PMD diagnostics. Expert opinion: We anticipate that the application of PCR-free WGS from blood DNA will increase in diagnostic laboratories, while for adults with myopathic presentations, WGS from muscle DNA may become more widespread. Improved bioinformatic strategies will enhance WGS data interrogation, with more accurate delineation of mtDNA and NUMTs (nuclear mitochondrial DNA segments) in WGS data, superior coverage uniformity, indirect measurement of mtDNA copy number, and more accurate interpretation of heteroplasmic large-scale rearrangements (LSRs). Separately, the adoption of diagnostic long-read sequencing could offer greater resolution of complex LSRs and the opportunity to phase heteroplasmic variants