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Pressure overload in patients with aortic valve stenosis and volume overload in mitral valve regurgitation trigger specific forms of cardiac remodeling; however, little is known about similarities and differences in myocardial proteome regulation. We performed proteome profiling of 75 human left ventricular myocardial biopsies (aortic stenosis = 41, mitral regurgitation = 17, and controls = 17) using high-resolution tandem mass spectrometry next to clinical and hemodynamic parameter acquisition. In patients of both disease groups, proteins related to ECM and cytoskeleton were more abundant, whereas those related to energy metabolism and proteostasis were less abundant compared with controls. In addition, disease group-specific and sex-specific differences have been observed. Male patients with aortic stenosis showed more proteins related to fibrosis and less to energy metabolism, whereas female patients showed strong reduction in proteostasis-related proteins. Clinical imaging was in line with proteomic findings, showing elevation of fibrosis in both patient groups and sex differences. Disease-and sex-specific proteomic profiles provide insight into cardiac remodeling in patients with heart valve disease and might help improve the understanding of molecular mechanisms and the development of individualized treatment strategies.
High annotation costs are a substantial bottleneck in applying deep learning architectures to clinically relevant use cases, substantiating the need for algorithms to learn from unlabeled data.
In this work, we propose employing self-supervised methods. To that end, we trained with three self-supervised algorithms on a large corpus of unlabeled dental images, which contained 38K bitewing radiographs (BWRs). We then applied the learned neural network representations on tooth-level dental caries classification, for which we utilized labels extracted from electronic health records (EHRs). Finally, a holdout test-set was established, which consisted of 343 BWRs and was annotated by three dental professionals and approved by a senior dentist.
This test-set was used to evaluate the fine-tuned caries classification models. Our experimental results demonstrate the obtained gains by pretraining models using self-supervised algorithms. These include improved caries classification performance (6 p.p. increase in sensitivity) and, most importantly, improved label-efficiency.
In other words, the resulting models can be fine-tuned using few labels (annotations).
Our results show that using as few as 18 annotations can produce >= 45% sensitivity, which is comparable to human-level diagnostic performance.
This study shows that self-supervision can provide gains in medical image analysis, particularly when obtaining labels is costly and expensive.
Fragmentation of peptides leaves characteristic patterns in mass spectrometry data, which can be used to identify protein sequences, but this method is challenging for mutated or modified sequences for which limited information exist. Altenburg et al. use an ad hoc learning approach to learn relevant patterns directly from unannotated fragmentation spectra.
Mass spectrometry-based proteomics provides a holistic snapshot of the entire protein set of living cells on a molecular level. Currently, only a few deep learning approaches exist that involve peptide fragmentation spectra, which represent partial sequence information of proteins.
Commonly, these approaches lack the ability to characterize less studied or even unknown patterns in spectra because of their use of explicit domain knowledge.
Here, to elevate unrestricted learning from spectra, we introduce 'ad hoc learning of fragmentation' (AHLF), a deep learning model that is end-to-end trained on 19.2 million spectra from several phosphoproteomic datasets. AHLF is interpretable, and we show that peak-level feature importance values and pairwise interactions between peaks are in line with corresponding peptide fragments.
We demonstrate our approach by detecting post-translational modifications, specifically protein phosphorylation based on only the fragmentation spectrum without a database search. AHLF increases the area under the receiver operating characteristic curve (AUC) by an average of 9.4% on recent phosphoproteomic data compared with the current state of the art on this task.
Furthermore, use of AHLF in rescoring search results increases the number of phosphopeptide identifications by a margin of up to 15.1% at a constant false discovery rate. To show the broad applicability of AHLF, we use transfer learning to also detect cross-linked peptides, as used in protein structure analysis, with an AUC of up to 94%.
Modern data analysis tasks often involve control flow statements, such as the iterations in PageRank and K-means. To achieve scalability, developers usually implement these tasks in distributed dataflow systems, such as Spark and Flink. Designers of such systems have to choose between providing imperative or functional control flow constructs to users. Imperative constructs are easier to use, but functional constructs are easier to compile to an efficient dataflow job. We propose Mitos, a system where control flow is both easy to use and efficient. Mitos relies on an intermediate representation based on the static single assignment form. This allows us to abstract away from specific control flow constructs and treat any imperative control flow uniformly both when building the dataflow job and when coordinating the distributed execution.
N-of-1 trials are the gold standard study design to evaluate individual treatment effects and derive personalized treatment strategies. Digital tools have the potential to initiate a new era of N-of-1 trials in terms of scale and scope, but fully functional platforms are not yet available.
Here, we present the open source StudyU platform, which includes the StudyU Designer and StudyU app.
With the StudyU Designer, scientists are given a collaborative web application to digitally specify, publish, and conduct N-of-1 trials.
The StudyU app is a smartphone app with innovative user-centric elements for participants to partake in trials published through the StudyU Designer to assess the effects of different interventions on their health.
Thereby, the StudyU platform allows clinicians and researchers worldwide to easily design and conduct digital N-of-1 trials in a safe manner.
We envision that StudyU can change the landscape of personalized treatments both for patients and healthy individuals, democratize and personalize evidence generation for self-optimization and medicine, and can be integrated in clinical practice.
The investigation of metabolic fluxes and metabolite distributions within cells by means of tracer molecules is a valuable tool to unravel the complexity of biological systems. Technological advances in mass spectrometry (MS) technology such as atmospheric pressure chemical ionization (APCI) coupled with high resolution (HR), not only allows for highly sensitive analyses but also broadens the usefulness of tracer-based experiments, as interesting signals can be annotated de novo when not yet present in a compound library. However, several effects in the APCI ion source, i.e., fragmentation and rearrangement, lead to superimposed mass isotopologue distributions (MID) within the mass spectra, which need to be corrected during data evaluation as they will impair enrichment calculation otherwise. Here, we present and evaluate a novel software tool to automatically perform such corrections. We discuss the different effects, explain the implemented algorithm, and show its application on several experimental datasets. This adjustable tool is available as an R package from CRAN.
Ion-mobility spectrometry shows great promise to tackle analytically challenging research questions by adding another separation dimension to liquid chromatography-mass spectrometry.
The understanding of how analyte properties influence ion mobility has increased through recent studies, but no clear rationale for the design of customized experimental settings has emerged.
Here, we leverage machine learning to deepen our understanding of field asymmetric waveform ion-mobility spectrometry for the analysis of cross-linked peptides.
Knowing that predominantly m/z and then the size and charge state of an analyte influence the separation, we found ideal compensation voltages correlating with the size exclusion chromatography fraction number.
The effect of this relationship on the analytical depth can be substantial as exploiting it allowed us to almost double unique residue pair detections in a proteome-wide cross-linking experiment.
Other applications involving liquid- and gas-phase separation may also benefit from considering such parameter dependencies.
Modern data analysis tasks often involve control flow statements, such as the iterations in PageRank and K-means. To achieve scalability, developers usually implement these tasks in distributed dataflow systems, such as Spark and Flink. Designers of such systems have to choose between providing imperative or functional control flow constructs to users. Imperative constructs are easier to use, but functional constructs are easier to compile to an efficient dataflow job. We propose Mitos, a system where control flow is both easy to use and efficient. Mitos relies on an intermediate representation based on the static single assignment form. This allows us to abstract away from specific control flow constructs and treat any imperative control flow uniformly both when building the dataflow job and when coordinating the distributed execution.
In his article, 'Social constructionism and climate science denial', Hansson claims to present empirical evidence that the cultural theory developed by Dame Mary Douglas, Aaron Wildavsky and ourselves (among others) leads to (climate) science denial. In this reply, we show that there is no validity to these claims. First, we show that Hansson's empirical evidence that cultural theory has led to climate science denial falls apart under closer inspection. Contrary to Hansson's claims, cultural theory has made significant contributions to understanding and addressing climate change. Second, we discuss various features of Douglas' cultural theory that differentiate it from other constructivist approaches and make it compatible with the scientific method. Thus, we also demonstrate that cultural theory cannot be accused of epistemic relativism.
Data encoding has been applied to database systems for decades as it mitigates bandwidth bottlenecks and reduces storage requirements. But even in the presence of these advantages, most in-memory database systems use data encoding only conservatively as the negative impact on runtime performance can be severe. Real-world systems with large parts being infrequently accessed and cost efficiency constraints in cloud environments require solutions that automatically and efficiently select encoding techniques, including heavy-weight compression. In this paper, we introduce workload-driven approaches to automaticaly determine memory budget-constrained encoding configurations using greedy heuristics and linear programming. We show for TPC-H, TPC-DS, and the Join Order Benchmark that optimized encoding configurations can reduce the main memory footprint significantly without a loss in runtime performance over state-of-the-art dictionary encoding. To yield robust selections, we extend the linear programming-based approach to incorporate query runtime constraints and mitigate unexpected performance regressions.
How inclusive are we?
(2022)
ACM SIGMOD, VLDB and other database organizations have committed to fostering an inclusive and diverse community, as do many other scientific organizations. Recently, different measures have been taken to advance these goals, especially for underrepresented groups. One possible measure is double-blind reviewing, which aims to hide gender, ethnicity, and other properties of the authors. <br /> We report the preliminary results of a gender diversity analysis of publications of the database community across several peer-reviewed venues, and also compare women's authorship percentages in both single-blind and double-blind venues along the years. We also obtained a cross comparison of the obtained results in data management with other relevant areas in Computer Science.
Fast style transfer methods have recently gained popularity in art-related applications as they make a generalized real-time stylization of images practicable. However, they are mostly limited to one-shot stylizations concerning the interactive adjustment of style elements. In particular, the expressive control over stroke sizes or stroke orientations remains an open challenge. To this end, we propose a novel stroke-adjustable fast style transfer network that enables simultaneous control over the stroke size and intensity, and allows a wider range of expressive editing than current approaches by utilizing the scale-variance of convolutional neural networks. Furthermore, we introduce a network-agnostic approach for style-element editing by applying reversible input transformations that can adjust strokes in the stylized output. At this, stroke orientations can be adjusted, and warping-based effects can be applied to stylistic elements, such as swirls or waves. To demonstrate the real-world applicability of our approach, we present StyleTune, a mobile app for interactive editing of neural style transfers at multiple levels of control. Our app allows stroke adjustments on a global and local level. It furthermore implements an on-device patch-based upsampling step that enables users to achieve results with high output fidelity and resolutions of more than 20 megapixels. Our approach allows users to art-direct their creations and achieve results that are not possible with current style transfer applications.
Correction to: Knowledge bases and software support for variant interpretation in precision oncology
(2021)
Precision oncology is a rapidly evolving interdisciplinary medical specialty. Comprehensive cancer panels are becoming increasingly available at pathology departments worldwide, creating the urgent need for scalable cancer variant annotation and molecularly informed treatment recommendations. A wealth of mainly academia-driven knowledge bases calls for software tools supporting the multi-step diagnostic process. We derive a comprehensive list of knowledge bases relevant for variant interpretation by a review of existing literature followed by a survey among medical experts from university hospitals in Germany. In addition, we review cancer variant interpretation tools, which integrate multiple knowledge bases. We categorize the knowledge bases along the diagnostic process in precision oncology and analyze programmatic access options as well as the integration of knowledge bases into software tools. The most commonly used knowledge bases provide good programmatic access options and have been integrated into a range of software tools. For the wider set of knowledge bases, access options vary across different parts of the diagnostic process. Programmatic access is limited for information regarding clinical classifications of variants and for therapy recommendations. The main issue for databases used for biological classification of pathogenic variants and pathway context information is the lack of standardized interfaces. There is no single cancer variant interpretation tool that integrates all identified knowledge bases. Specialized tools are available and need to be further developed for different steps in the diagnostic process.
In clinical practice, only a few reliable measurement instruments are available for monitoring knee joint rehabilitation. Advances to replace motion capturing with sensor data measurement have been made in the last years. Thus, a systematic review of the literature was performed, focusing on the implementation, diagnostic accuracy, and facilitators and barriers of integrating wearable sensor technology in clinical practices based on a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. For critical appraisal, the COSMIN Risk of Bias tool for reliability and measurement of error was used. PUBMED, Prospero, Cochrane database, and EMBASE were searched for eligible studies. Six studies reporting reliability aspects in using wearable sensor technology at any point after knee surgery in humans were included. All studies reported excellent results with high reliability coefficients, high limits of agreement, or a few detectable errors. They used different or partly inappropriate methods for estimating reliability or missed reporting essential information. Therefore, a moderate risk of bias must be considered. Further quality criterion studies in clinical settings are needed to synthesize the evidence for providing transparent recommendations for the clinical use of wearable movement sensors in knee joint rehabilitation.
FIBER
(2021)
Objectives:
The development of clinical predictive models hinges upon the availability of comprehensive clinical data. Tapping into such resources requires considerable effort from clinicians, data scientists, and engineers. Specifically, these efforts are focused on data extraction and preprocessing steps required prior to modeling, including complex database queries. A handful of software libraries exist that can reduce this complexity by building upon data standards. However, a gap remains concerning electronic health records (EHRs) stored in star schema clinical data warehouses, an approach often adopted in practice. In this article, we introduce the FlexIBle EHR Retrieval (FIBER) tool: a Python library built on top of a star schema (i2b2) clinical data warehouse that enables flexible generation of modeling-ready cohorts as data frames.
Materials and Methods:
FIBER was developed on top of a large-scale star schema EHR database which contains data from 8 million patients and over 120 million encounters. To illustrate FIBER's capabilities, we present its application by building a heart surgery patient cohort with subsequent prediction of acute kidney injury (AKI) with various machine learning models.
Results:
Using FIBER, we were able to build the heart surgery cohort (n = 12 061), identify the patients that developed AKI (n = 1005), and automatically extract relevant features (n = 774). Finally, we trained machine learning models that achieved area under the curve values of up to 0.77 for this exemplary use case.
Conclusion:
FIBER is an open-source Python library developed for extracting information from star schema clinical data warehouses and reduces time-to-modeling, helping to streamline the clinical modeling process.