TY - JOUR A1 - Nordmeyer, Sarah A1 - Kraus, Milena A1 - Ziehm, Matthias A1 - Kirchner, Marieluise A1 - Schafstedde, Marie A1 - Kelm, Marcus A1 - Niquet, Sylvia A1 - Stephen, Mariet Mathew A1 - Baczko, Istvan A1 - Knosalla, Christoph A1 - Schapranow, Matthieu-Patrick A1 - Dittmar, Gunnar A1 - Gotthardt, Michael A1 - Falcke, Martin A1 - Regitz-Zagrosek, Vera A1 - Kuehne, Titus A1 - Mertins, Philipp T1 - Disease- and sex-specific differences in patients with heart valve disease BT - a proteome study JF - Life Science Alliance N2 - 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. Y1 - 2023 U6 - https://doi.org/10.26508/lsa.202201411 SN - 2575-1077 VL - 6 IS - 3 PB - EMBO Press CY - Heidelberg ER - TY - JOUR A1 - Taleb, Aiham A1 - Rohrer, Csaba A1 - Bergner, Benjamin A1 - De Leon, Guilherme A1 - Rodrigues, Jonas Almeida A1 - Schwendicke, Falk A1 - Lippert, Christoph A1 - Krois, Joachim T1 - Self-supervised learning methods for label-efficient dental caries classification JF - Diagnostics : open access journal N2 - 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. KW - unsupervised methods KW - self-supervised learning KW - representation learning KW - dental caries classification KW - data driven approaches KW - annotation KW - efficient deep learning Y1 - 2022 U6 - https://doi.org/10.3390/diagnostics12051237 SN - 2075-4418 VL - 12 IS - 5 PB - MDPI CY - Basel ER - TY - GEN A1 - Tang, Mitchell A1 - Nakamoto, Carter H. A1 - Stern, Ariel Dora A1 - Mehrotra, Ateev T1 - Trends in remote patient monitoring use in traditional medicare T2 - JAMA internal medicine Y1 - 2022 U6 - https://doi.org/10.1001/jamainternmed.2022.3043 SN - 2168-6106 SN - 2168-6114 VL - 182 IS - 9 SP - 1005 EP - 1006 PB - American Medical Association CY - Chicago, Ill. ER - TY - JOUR A1 - Altenburg, Tom A1 - Giese, Sven Hans-Joachim A1 - Wang, Shengbo A1 - Muth, Thilo A1 - Renard, Bernhard Y. T1 - Ad hoc learning of peptide fragmentation from mass spectra enables an interpretable detection of phosphorylated and cross-linked peptides JF - Nature machine intelligence N2 - 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%. Y1 - 2022 U6 - https://doi.org/10.1038/s42256-022-00467-7 SN - 2522-5839 VL - 4 IS - 4 SP - 378 EP - 388 PB - Springer Nature Publishing CY - London ER - TY - JOUR A1 - Gévay, Gábor E. A1 - Rabl, Tilmann A1 - Breß, Sebastian A1 - Madai-Tahy, Loránd A1 - Quiané-Ruiz, Jorge-Arnulfo A1 - Markl, Volker T1 - Imperative or functional control flow handling BT - why not the best of both worlds? JF - SIGMOD record / Association for Computing Machinery, Special Interest Group on Management of Data N2 - 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. Y1 - 2022 U6 - https://doi.org/10.1145/3542700.3542715 SN - 0163-5808 VL - 51 IS - 1 SP - 60 EP - 67 PB - Association for Computing Machinery CY - New York ER - TY - JOUR A1 - Konigorski, Stefan A1 - Wernicke, Sarah A1 - Slosarek, Tamara A1 - Zenner, Alexander M. A1 - Strelow, Nils A1 - Ruether, Darius F. A1 - Henschel, Florian A1 - Manaswini, Manisha A1 - Pottbäcker, Fabian A1 - Edelman, Jonathan A. A1 - Owoyele, Babajide A1 - Danieletto, Matteo A1 - Golden, Eddye A1 - Zweig, Micol A1 - Nadkarni, Girish N. A1 - Böttinger, Erwin T1 - StudyU: a platform for designing and conducting innovative digital N-of-1 trials JF - Journal of medical internet research N2 - 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. KW - digital interventions KW - N-of-1 trial KW - SCED KW - single-case experimental design KW - web application KW - mobile application KW - app KW - digital health Y1 - 2022 U6 - https://doi.org/10.2196/35884 SN - 1439-4456 SN - 1438-8871 VL - 24 IS - 7 PB - Healthcare World CY - Richmond, Va. ER - TY - GEN A1 - Dellepiane, Sergio A1 - Vaid, Akhil A1 - Jaladanki, Suraj K. A1 - Coca, Steven A1 - Fayad, Zahi A. A1 - Charney, Alexander W. A1 - Böttinger, Erwin A1 - He, John Cijiang A1 - Glicksberg, Benjamin S. A1 - Chan, Lili A1 - Nadkarni, Girish T1 - Acute kidney injury in patients hospitalized with COVID-19 in New York City BT - Temporal Trends From March 2020 to April 2021 T2 - Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät T3 - Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät - 21 Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-585415 SN - 2590-0595 IS - 5 ER - TY - JOUR A1 - Langenhan, Jennifer A1 - Jaeger, Carsten A1 - Baum, Katharina A1 - Simon, Mareike A1 - Lisec, Jan T1 - A flexible tool to correct superimposed mass isotopologue distributions in GC-APCI-MS flux experiments JF - Metabolites N2 - 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. KW - mass isotopologue distribution KW - enrichment calculation KW - flux KW - experiments KW - atmospheric pressure chemical ionization KW - R package KW - CorMID Y1 - 2022 U6 - https://doi.org/10.3390/metabo12050408 SN - 2218-1989 VL - 12 IS - 5 PB - MDPI CY - Basel ER - TY - JOUR A1 - Sinn, Ludwig R. A1 - Giese, Sven Hans-Joachim A1 - Stuiver, Marchel A1 - Rappsilber, Juri T1 - Leveraging parameter dependencies in high-field asymmetric waveform ion-mobility spectrometry and size exclusion chromatography for proteome-wide cross-linking mass spectrometry JF - Analytical chemistry : the authoritative voice of the analytical community N2 - 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. Y1 - 2022 U6 - https://doi.org/10.1021/acs.analchem.1c04373 SN - 0003-2700 SN - 1520-6882 VL - 94 IS - 11 SP - 4627 EP - 4634 PB - American Chemical Society CY - Columbus, Ohio ER - TY - JOUR A1 - Gevay, Gabor E. A1 - Rabl, Tilmann A1 - Bress, Sebastian A1 - Maclai-Tahy, Lorand A1 - Quiane-Ruiz, Jorge-Arnulfo A1 - Markl, Volker T1 - Imperative or Functional Control Flow Handling: Why not the Best of Both Worlds? JF - SIGMOD record N2 - 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. Y1 - 2022 U6 - https://doi.org/10.1109/ICDE51399.2021.00127 SN - 0163-5808 SN - 1943-5835 VL - 51 IS - 1 SP - 60 EP - 67 PB - Association for Computing Machinery CY - New York ER -