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- Hasso-Plattner-Institut für Digital Engineering GmbH (22) (entfernen)
The transversal hypergraph problem asks to enumerate the minimal hitting sets of a hypergraph. If the solutions have bounded size, Eiter and Gottlob [SICOMP'95] gave an algorithm running in output-polynomial time, but whose space requirement also scales with the output. We improve this to polynomial delay and space. Central to our approach is the extension problem, deciding for a set X of vertices whether it is contained in any minimal hitting set. We show that this is one of the first natural problems to be W[3]-complete. We give an algorithm for the extension problem running in time O(m(vertical bar X vertical bar+1) n) and prove a SETH-lower bound showing that this is close to optimal. We apply our enumeration method to the discovery problem of minimal unique column combinations from data profiling. Our empirical evaluation suggests that the algorithm outperforms its worst-case guarantees on hypergraphs stemming from real-world databases.
The question if a given partial solution to a problem can be extended reasonably occurs in many algorithmic approaches for optimization problems.
For instance, when enumerating minimal vertex covers of a graph G = (V, E), one usually arrives at the problem to decide for a vertex set U subset of V (pre-solution), if there exists a minimal vertex cover S (i.e., a vertex cover S subset of V such that no proper subset of S is a vertex cover) with U subset of S (minimal extension of U).
We propose a general, partial-order based formulation of such extension problems which allows to model parameterization and approximation aspects of extension, and also highlights relationships between extension tasks for different specific problems.
As examples, we study a number of specific problems which can be expressed and related in this framework. In particular, we discuss extension variants of the problems dominating set and feedback vertex/edge set.
All these problems are shown to be NP-complete even when restricted to bipartite graphs of bounded degree, with the exception of our extension version of feedback edge set on undirected graphs which is shown to be solvable in polynomial time.
For the extension variants of dominating and feedback vertex set, we also show NP-completeness for the restriction to planar graphs of bounded degree.
As non-graph problem, we also study an extension version of the bin packing problem. We further consider the parameterized complexity of all these extension variants, where the parameter is a measure of the pre-solution as defined by our framework.
We present fully polynomial time approximation schemes for a broad class of Holant problems with complex edge weights, which we call Holant polynomials. We transform these problems into partition functions of abstract combinatorial structures known as polymers in statistical physics. Our method involves establishing zero-free regions for the partition functions of polymer models and using the most significant terms of the cluster expansion to approximate them. Results of our technique include new approximation and sampling algorithms for a diverse class of Holant polynomials in the low-temperature regime (i.e. small external field) and approximation algorithms for general Holant problems with small signature weights. Additionally, we give randomised approximation and sampling algorithms with faster running times for more restrictive classes. Finally, we improve the known zero-free regions for a perfect matching polynomial.
A path in an edge-colored graph is rainbow if no two edges of it are colored the same, and the graph is rainbow-connected if there is a rainbow path between each pair of its vertices. The minimum number of colors needed to rainbow-connect a graph G is the rainbow connection number of G, denoted by rc(G).& nbsp;A simple way to rainbow-connect a graph G is to color the edges of a spanning tree with distinct colors and then re-use any of these colors to color the remaining edges of G. This proves that rc(G) <= |V (G)|-1. We ask whether there is a stronger connection between tree-like structures and rainbow coloring than that is implied by the above trivial argument. For instance, is it possible to find an upper bound of t(G)-1 for rc(G), where t(G) is the number of vertices in the largest induced tree of G? The answer turns out to be negative, as there are counter-examples that show that even c .t(G) is not an upper bound for rc(G) for any given constant c.& nbsp;In this work we show that if we consider the forest number f(G), the number of vertices in a maximum induced forest of G, instead of t(G), then surprisingly we do get an upper bound. More specifically, we prove that rc(G) <= f(G) + 2. Our result indicates a stronger connection between rainbow connection and tree-like structures than that was suggested by the simple spanning tree based upper bound.
Law smells
(2022)
Building on the computer science concept of code smells, we initiate the study of law smells, i.e., patterns in legal texts that pose threats to the comprehensibility and maintainability of the law. With five intuitive law smells as running examples-namely, duplicated phrase, long element, large reference tree, ambiguous syntax, and natural language obsession-, we develop a comprehensive law smell taxonomy. This taxonomy classifies law smells by when they can be detected, which aspects of law they relate to, and how they can be discovered. We introduce text-based and graph-based methods to identify instances of law smells, confirming their utility in practice using the United States Code as a test case. Our work demonstrates how ideas from software engineering can be leveraged to assess and improve the quality of legal code, thus drawing attention to an understudied area in the intersection of law and computer science and highlighting the potential of computational legal drafting.
Industry 4.0 is transforming how businesses innovate and, as a result, companies are spearheading the movement towards 'Digital Transformation'. While some scholars advocate the use of design thinking to identify new innovative behaviours, cognition experts emphasise the importance of top managers in supporting employees to develop these behaviours. However, there is a dearth of research in this domain and companies are struggling to implement the required behaviours. To address this gap, this study aims to identify and prioritise behavioural strategies conducive to design thinking to inform the creation of a managerial mental model. We identify 20 behavioural strategies from 45 interviewees with practitioners and educators and combine them with the concepts of 'paradigm-mindset-mental model' from cognition theory. The paper contributes to the body of knowledge by identifying and prioritising specific behavioural strategies to form a novel set of survival conditions aligned to the new industrial paradigm of Industry 4.0.
Piloting a Survey-Based Assessment of Transparency and Trustworthiness with Three Medical AI Tools
(2022)
Artificial intelligence (AI) offers the potential to support healthcare delivery, but poorly trained or validated algorithms bear risks of harm. Ethical guidelines stated transparency about model development and validation as a requirement for trustworthy AI. Abundant guidance exists to provide transparency through reporting, but poorly reported medical AI tools are common. To close this transparency gap, we developed and piloted a framework to quantify the transparency of medical AI tools with three use cases. Our framework comprises a survey to report on the intended use, training and validation data and processes, ethical considerations, and deployment recommendations. The transparency of each response was scored with either 0, 0.5, or 1 to reflect if the requested information was not, partially, or fully provided. Additionally, we assessed on an analogous three-point scale if the provided responses fulfilled the transparency requirement for a set of trustworthiness criteria from ethical guidelines. The degree of transparency and trustworthiness was calculated on a scale from 0% to 100%. Our assessment of three medical AI use cases pin-pointed reporting gaps and resulted in transparency scores of 67% for two use cases and one with 59%. We report anecdotal evidence that business constraints and limited information from external datasets were major obstacles to providing transparency for the three use cases. The observed transparency gaps also lowered the degree of trustworthiness, indicating compliance gaps with ethical guidelines. All three pilot use cases faced challenges to provide transparency about medical AI tools, but more studies are needed to investigate those in the wider medical AI sector. Applying this framework for an external assessment of transparency may be infeasible if business constraints prevent the disclosure of information. New strategies may be necessary to enable audits of medical AI tools while preserving business secrets.
Human observer net
(2022)
Background:
Current software applications for human observer studies of images lack flexibility in study design, platform independence, multicenter use, and assessment methods and are not open source, limiting accessibility and expandability.
Purpose:
To develop a user-friendly software platform that enables efficient human observer studies in medical imaging with flexibility of study design.
Materials and Methods:
Software for human observer imaging studies was designed as an open-source web application to facilitate access, platform-independent usability, and multicenter studies. Different interfaces for study creation, participation, and management of results were implemented. The software was evaluated in human observer experiments between May 2019 and March 2021, in which duration of observer responses was tracked. Fourteen radiologists evaluated and graded software usability using the 100-point system usability scale. The application was tested in Chrome, Firefox, Safari, and Edge browsers.
Results:
Software function was designed to allow visual grading analysis (VGA), multiple-alternative forced-choice (m-AFC), receiver operating characteristic (ROC), localization ROC, free-response ROC, and customized designs. The mean duration of reader responses per image or per image set was 6.2 seconds 6 4.8 (standard deviation), 5.8 seconds 6 4.7, 8.7 seconds 6 5.7, and 6.0 seconds 6 4.5 in four-AFC with 160 image quartets per reader, four-AFC with 640 image quartets per reader, localization ROC, and experimental studies, respectively. The mean system usability scale score was 83 6 11 (out of 100). The documented code and a demonstration of the application are available online (https://github.com/genskeu/HON, https://hondemo.pythonanywhere.com/).
Conclusion:
A user-friendly and efficient open-source application was developed for human reader experiments that enables study design versatility, as well as platform-independent and multicenter usability.
In discrete manufacturing, the knowledge about causal relationships makes it possible to avoid unforeseen production downtimes by identifying their root causes. Learning causal structures from real-world settings remains challenging due to high-dimensional data, a mix of discrete and continuous variables, and requirements for preprocessing log data under the causal perspective. In our work, we address these challenges proposing a process for causal reasoning based on raw machine log data from production monitoring. Within this process, we define a set of transformation rules to extract independent and identically distributed observations. Further, we incorporate a variable selection step to handle high-dimensionality and a discretization step to include continuous variables. We enrich a commonly used causal structure learning algorithm with domain-related orientation rules, which provides a basis for causal reasoning. We demonstrate the process on a real-world dataset from a globally operating precision mechanical engineering company. The dataset contains over 40 million log data entries from production monitoring of a single machine. In this context, we determine the causal structures embedded in operational processes. Further, we examine causal effects to support machine operators in avoiding unforeseen production stops, i.e., by detaining machine operators from drawing false conclusions on impacting factors of unforeseen production stops based on experience.
Quantifying neurological disorders from voice is a rapidly growing field of research and holds promise for unobtrusive and large-scale disorder monitoring. The data recording setup and data analysis pipelines are both crucial aspects to effectively obtain relevant information from participants. Therefore, we performed a systematic review to provide a high-level overview of practices across various neurological disorders and highlight emerging trends. PRISMA-based literature searches were conducted through PubMed, Web of Science, and IEEE Xplore to identify publications in which original (i.e., newly recorded) datasets were collected. Disorders of interest were psychiatric as well as neurodegenerative disorders, such as bipolar disorder, depression, and stress, as well as amyotrophic lateral sclerosis amyotrophic lateral sclerosis, Alzheimer's, and Parkinson's disease, and speech impairments (aphasia, dysarthria, and dysphonia). Of the 43 retrieved studies, Parkinson's disease is represented most prominently with 19 discovered datasets. Free speech and read speech tasks are most commonly used across disorders. Besides popular feature extraction toolkits, many studies utilise custom-built feature sets. Correlations of acoustic features with psychiatric and neurodegenerative disorders are presented. In terms of analysis, statistical analysis for significance of individual features is commonly used, as well as predictive modeling approaches, especially with support vector machines and a small number of artificial neural networks. An emerging trend and recommendation for future studies is to collect data in everyday life to facilitate longitudinal data collection and to capture the behavior of participants more naturally. Another emerging trend is to record additional modalities to voice, which can potentially increase analytical performance.
In liquid-chromatography-tandem-mass-spectrometry-based proteomics, information about the presence and stoichiometry ofprotein modifications is not readily available. To overcome this problem,we developed multiFLEX-LF, a computational tool that builds uponFLEXIQuant, which detects modified peptide precursors and quantifiestheir modification extent by monitoring the differences between observedand expected intensities of the unmodified precursors. multiFLEX-LFrelies on robust linear regression to calculate the modification extent of agiven precursor relative to a within-study reference. multiFLEX-LF cananalyze entire label-free discovery proteomics data sets in a precursor-centric manner without preselecting a protein of interest. To analyzemodification dynamics and coregulated modifications, we hierarchicallyclustered the precursors of all proteins based on their computed relativemodification scores. We applied multiFLEX-LF to a data-independent-acquisition-based data set acquired using the anaphase-promoting complex/cyclosome (APC/C) isolated at various time pointsduring mitosis. The clustering of the precursors allows for identifying varying modification dynamics and ordering the modificationevents. Overall, multiFLEX-LF enables the fast identification of potentially differentially modified peptide precursors and thequantification of their differential modification extent in large data sets using a personal computer. Additionally, multiFLEX-LF candrive the large-scale investigation of the modification dynamics of peptide precursors in time-series and case-control studies.multiFLEX-LF is available athttps://gitlab.com/SteenOmicsLab/multiflex-lf.
As resources are valuable assets, organizations have to decide which resources to allocate to business process tasks in a way that the process is executed not only effectively but also efficiently. Traditional role-based resource allocation leads to effective process executions, since each task is performed by a resource that has the required skills and competencies to do so. However, the resulting allocations are typically not as efficient as they could be, since optimization techniques have yet to find their way in traditional business process management scenarios. On the other hand, operations research provides a rich set of analytical methods for supporting problem-specific decisions on resource allocation. This paper provides a novel framework for creating transparency on existing tasks and resources, supporting individualized allocations for each activity in a process, and the possibility to integrate problem-specific analytical methods of the operations research domain. To validate the framework, the paper reports on the design and prototypical implementation of a software architecture, which extends a traditional process engine with a dedicated resource management component. This component allows us to define specific resource allocation problems at design time, and it also facilitates optimized resource allocation at run time. The framework is evaluated using a real-world parcel delivery process. The evaluation shows that the quality of the allocation results increase significantly with a technique from operations research in contrast to the traditional applied rule-based approach.
Process mining techniques are valuable to gain insights into and help improve (work) processes. Many of these techniques focus on the sequential order in which activities are performed. Few of these techniques consider the statistical relations within processes. In particular, existing techniques do not allow insights into how responses to an event (action) result in desired or undesired outcomes (effects). We propose and formalize the ARE miner, a novel technique that allows us to analyze and understand these action-response-effect patterns. We take a statistical approach to uncover potential dependency relations in these patterns. The goal of this research is to generate processes that are: (1) appropriately represented, and (2) effectively filtered to show meaningful relations. We evaluate the ARE miner in two ways. First, we use an artificial data set to demonstrate the effectiveness of the ARE miner compared to two traditional process-oriented approaches. Second, we apply the ARE miner to a real-world data set from a Dutch healthcare institution. We show that the ARE miner generates comprehensible representations that lead to informative insights into statistical relations between actions, responses, and effects.
Here we present an exome-wide rare genetic variant association study for 30 blood biomarkers in 191,971 individuals in the UK Biobank. We compare gene- based association tests for separate functional variant categories to increase interpretability and identify 193 significant gene-biomarker associations. Genes associated with biomarkers were ~ 4.5-fold enriched for conferring Mendelian disorders. In addition to performing weighted gene-based variant collapsing tests, we design and apply variant-category-specific kernel-based tests that integrate quantitative functional variant effect predictions for mis- sense variants, splicing and the binding of RNA-binding proteins. For these tests, we present a computationally efficient combination of the likelihood- ratio and score tests that found 36% more associations than the score test alone while also controlling the type-1 error. Kernel-based tests identified 13% more associations than their gene-based collapsing counterparts and had advantages in the presence of gain of function missense variants. We introduce local collapsing by amino acid position for missense variants and use it to interpret associations and identify potential novel gain of function variants in PIEZO1. Our results show the benefits of investigating different functional mechanisms when performing rare-variant association tests, and demonstrate pervasive rare-variant contribution to biomarker variability.
Omics and male infertility
(2022)
Male infertility is a multifaceted disorder affecting approximately 50% of male partners in infertile couples.
Over the years, male infertility has been diagnosed mainly through semen analysis, hormone evaluations, medical records and physical examinations, which of course are fundamental, but yet inefficient, because 30% of male infertility cases remain idiopathic. This dilemmatic status of the unknown needs to be addressed with more sophisticated and result-driven technologies and/or techniques.
Genetic alterations have been linked with male infertility, thereby unveiling the practicality of investigating this disorder from the "omics" perspective.
Omics aims at analyzing the structure and functions of a whole constituent of a given biological function at different levels, including the molecular gene level (genomics), transcript level (transcriptomics), protein level (proteomics) and metabolites level (metabolomics). In the current study, an overview of the four branches of omics and their roles in male infertility are briefly discussed; the potential usefulness of assessing transcriptomic data to understand this pathology is also elucidated.
After assessing the publicly obtainable transcriptomic data for datasets on male infertility, a total of 1385 datasets were retrieved, of which 10 datasets met the inclusion criteria and were used for further analysis.
These datasets were classified into groups according to the disease or cause of male infertility.
The groups include non-obstructive azoospermia (NOA), obstructive azoospermia (OA), non-obstructive and obstructive azoospermia (NOA and OA), spermatogenic dysfunction, sperm dysfunction, and Y chromosome microdeletion.
Findings revealed that 8 genes (LDHC, PDHA2, TNP1, TNP2, ODF1, ODF2, SPINK2, PCDHB3) were commonly differentially expressed between all disease groups.
Likewise, 56 genes were common between NOA versus NOA and OA (ADAD1, BANF2, BCL2L14, C12orf50, C20orf173, C22orf23, C6orf99, C9orf131, C9orf24, CABS1, CAPZA3, CCDC187, CCDC54, CDKN3, CEP170, CFAP206, CRISP2, CT83, CXorf65, FAM209A, FAM71F1, FAM81B, GALNTL5, GTSF1, H1FNT, HEMGN, HMGB4, KIF2B, LDHC, LOC441601, LYZL2, ODF1, ODF2, PCDHB3, PDHA2, PGK2, PIH1D2, PLCZ1, PROCA1, RIMBP3, ROPN1L, SHCBP1L, SMCP, SPATA16, SPATA19, SPINK2, TEX33, TKTL2, TMCO2, TMCO5A, TNP1, TNP2, TSPAN16, TSSK1B, TTLL2, UBQLN3).
These genes, particularly the above-mentioned 8 genes, are involved in diverse biological processes such as germ cell development, spermatid development, spermatid differentiation, regulation of proteolysis, spermatogenesis and metabolic processes.
Owing to the stage-specific expression of these genes, any mal-expression can ultimately lead to male infertility.
Therefore, currently available data on all branches of omics relating to male fertility can be used to identify biomarkers for diagnosing male infertility, which can potentially help in unravelling some idiopathic cases.
Based on the performance requirements of modern spatio-temporal data mining applications, in-memory database systems are often used to store and process the data. To efficiently utilize the scarce DRAM capacities, modern database systems support various tuning possibilities to reduce the memory footprint (e.g., data compression) or increase performance (e.g., additional indexes). However, the selection of cost and performance balancing configurations is challenging due to the vast number of possible setups consisting of mutually dependent individual decisions. In this paper, we introduce a novel approach to jointly optimize the compression, sorting, indexing, and tiering configuration for spatio-temporal workloads. Further, we consider horizontal data partitioning, which enables the independent application of different tuning options on a fine-grained level. We propose different linear programming (LP) models addressing cost dependencies at different levels of accuracy to compute optimized tuning configurations for a given workload and memory budgets. To yield maintainable and robust configurations, we extend our LP-based approach to incorporate reconfiguration costs as well as a worst-case optimization for potential workload scenarios. Further, we demonstrate on a real-world dataset that our models allow to significantly reduce the memory footprint with equal performance or increase the performance with equal memory size compared to existing tuning heuristics.
Many participants in Massive Open Online Courses are full-time employees seeking greater flexibility in their time commitment and the available learning paths. We recently addressed these requirements by splitting up our 6-week courses into three 2-week modules followed by a separate exam. Modularizing courses offers many advantages: Shorter modules are more sustainable and can be combined, reused, and incorporated into learning paths more easily. Time flexibility for learners is also improved as exams can now be offered multiple times per year, while the learning content is available independently. In this article, we answer the question of which impact this modularization has on key learning metrics, such as course completion rates, learning success, and no-show rates. Furthermore, we investigate the influence of longer breaks between modules on these metrics. According to our analysis, course modules facilitate more selective learning behaviors that encourage learners to focus on topics they are the most interested in. At the same time, participation in overarching exams across all modules seems to be less appealing compared to an integrated exam of a 6-week course. While breaks between the modules increase the distinctive appearance of individual modules, a break before the final exam further reduces initial interest in the exams. We further reveal that participation in self-paced courses as a preparation for the final exam is unlikely to attract new learners to the course offerings, even though learners' performance is comparable to instructor-paced courses. The results of our long-term study on course modularization provide a solid foundation for future research and enable educators to make informed decisions about the design of their courses.
ReadBouncer
(2022)
Motivation:
Nanopore sequencers allow targeted sequencing of interesting nucleotide sequences by rejecting other sequences from individual pores. This feature facilitates the enrichment of low-abundant sequences by depleting overrepresented ones in-silico. Existing tools for adaptive sampling either apply signal alignment, which cannot handle human-sized reference sequences, or apply read mapping in sequence space relying on fast graphical processing units (GPU) base callers for real-time read rejection. Using nanopore long-read mapping tools is also not optimal when mapping shorter reads as usually analyzed in adaptive sampling applications.
Results:
Here, we present a new approach for nanopore adaptive sampling that combines fast CPU and GPU base calling with read classification based on Interleaved Bloom Filters. ReadBouncer improves the potential enrichment of low abundance sequences by its high read classification sensitivity and specificity, outperforming existing tools in the field. It robustly removes even reads belonging to large reference sequences while running on commodity hardware without GPUs, making adaptive sampling accessible for in-field researchers. Readbouncer also provides a user-friendly interface and installer files for end-users without a bioinformatics background.
CovRadar
(2022)
The ongoing pandemic caused by SARS-CoV-2 emphasizes the importance of genomic surveillance to understand the evolution of the virus, to monitor the viral population, and plan epidemiological responses. Detailed analysis, easy visualization and intuitive filtering of the latest viral sequences are powerful for this purpose. We present CovRadar, a tool for genomic surveillance of the SARS-CoV-2 Spike protein. CovRadar consists of an analytical pipeline and a web application that enable the analysis and visualization of hundreds of thousand sequences. First, CovRadar extracts the regions of interest using local alignment, then builds a multiple sequence alignment, infers variants and consensus and finally presents the results in an interactive app, making accessing and reporting simple, flexible and fast.