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13 Publications visible to you, out of a total of 13
A liver digital twin for in silico testing of cellular and inter-cellular mechanisms in regeneration after drug-induced damage

Abstract

Not specified

Authors: Jieling Zhao, Ahmed Ghallab, Reham Hassan, Steven Dooley, Jan Georg Hengstler, Dirk Drasdo

Date Published: 1st Feb 2024

Publication Type: Journal

Gene regulatory network inference in the era of single-cell multi-omics

Abstract

Not specified

Authors: Pau Badia-i-Mompel, Lorna Wessels, Sophia Müller-Dott, Rémi Trimbour, Ricardo O. Ramirez Flores, Ricard Argelaguet, Julio Saez-Rodriguez

Date Published: 1st Nov 2023

Publication Type: Journal

Guided interactive image segmentation using machine learning and color-based image set clustering

Abstract (Expand)

Abstract Motivation Over the last decades, image processing and analysis have become one of the key technologies in systems biology and medicine. The quantification of anatomical structures and dynamic …The quantification of anatomical structures and dynamic processes in living systems is essential for understanding the complex underlying mechanisms and allows, i.e. the construction of spatio-temporal models that illuminate the interplay between architecture and function. Recently, deep learning significantly improved the performance of traditional image analysis in cases where imaging techniques provide large amounts of data. However, if only a few images are available or qualified annotations are expensive to produce, the applicability of deep learning is still limited. Results We present a novel approach that combines machine learning-based interactive image segmentation using supervoxels with a clustering method for the automated identification of similarly colored images in large image sets which enables a guided reuse of interactively trained classifiers. Our approach solves the problem of deteriorated segmentation and quantification accuracy when reusing trained classifiers which is due to significant color variability prevalent and often unavoidable in biological and medical images. This increase in efficiency improves the suitability of interactive segmentation for larger image sets, enabling efficient quantification or the rapid generation of training data for deep learning with minimal effort. The presented methods are applicable for almost any image type and represent a useful tool for image analysis tasks in general. Availability and implementation The presented methods are implemented in our image processing software TiQuant which is freely available at tiquant.hoehme.com. Supplementary information Supplementary data are available at Bioinformatics online.

Authors: Adrian Friebel, Tim Johann, Dirk Drasdo, Stefan Hoehme

Date Published: 1st Oct 2022

Publication Type: Journal

Non-Invasive Detection of Fibrotic NASH in NAFLD Patients with Low or Intermediate FIB-4

Abstract (Expand)

Background: Non-alcoholic steatohepatitis (NASH) and fibrosis are the main prognostic factors in non-alcoholic fatty liver disease (NAFLD). The FIB-4 score has been suggested as an initial test for the …l test for the exclusion of progressed fibrosis. However, increasing evidence suggests that also NASH patients with earlier fibrosis stages are at risk of disease progression, emphasizing the need for improved non-invasive risk stratification. Methods: We evaluated whether the apoptosis biomarker M30 can identify patients with fibrotic NASH despite low or intermediate FIB-4 values. Serum M30 levels were assessed by ELISA, and FIB-4 was calculated in an exploration (n = 103) and validation (n = 100) cohort of patients with histologically confirmed NAFLD. Results: The majority of patients with low FIB-4 (cut-off value < 1.3) in the exploration cohort revealed increased M30 levels (>200 U/L) and more than 80% of them had NASH, mostly with fibrosis. NASH was also detected in all patients with intermediate FIB-4 (1.3 to 2.67) and elevated M30, from which ~80% showed fibrosis. Importantly, in the absence of elevated M30, most patients with FIB-4 < 1.3 and NASH showed also no fibrosis. Similar results were obtained in the validation cohort. Conclusions: The combination of FIB-4 with M30 enables a more reliable identification of patients at risk for progressed NAFLD and might, therefore, improve patient stratification.

Authors: Katharina John, Martin Franck, Sherin Al Aoua, Monika Rau, Yvonne Huber, Joern M. Schattenberg, Andreas Geier, Matthias J. Bahr, Heiner Wedemeyer, Klaus Schulze-Osthoff, Heike Bantel

Date Published: 1st Aug 2022

Publication Type: Journal

Comparison of Three Xylose Pathways in Pseudomonas putida KT2440 for the Synthesis of Valuable Products

Abstract (Expand)

Pseudomonas putida KT2440 is a well-established chassis in industrial biotechnology. To increase the substrate spectrum, we implemented three alternative xylose utilization pathways, namely the Isomerase, … Weimberg, and Dahms pathways. The synthetic operons contain genes from Escherichia coli and Pseudomonas taiwanensis. For isolating the Dahms pathway in P. putida KT2440 two genes (PP_2836 and PP_4283), encoding an endogenous enzyme of the Weimberg pathway and a regulator for glycolaldehyde degradation, were deleted. Before and after adaptive laboratory evolution, these strains were characterized in terms of growth and synthesis of mono-rhamnolipids and pyocyanin. The engineered strain using the Weimberg pathway reached the highest maximal growth rate of 0.30 h−1. After adaptive laboratory evolution the lag phase was reduced significantly. The highest titers of 720mg L−1 mono-rhamnolipids and 30mg L−1 pyocyanin were reached by the evolved strain using the Weimberg or an engineered strain using the Isomerase pathway, respectively. The different stoichiometries of the three xylose utilization pathways may allow engineering of tailored chassis for valuable bioproduct synthesis.

Authors: Isabel Bator, Andreas Wittgens, Frank Rosenau, Till Tiso, Lars M. Blank

Date Published: 17th Jan 2020

Publication Type: Not specified

Data management and data enrichment for systems biology projects.

Abstract (Expand)

Collecting, curating, interlinking, and sharing high quality data are central to de.NBI-SysBio, the systems biology data management service center within the de.NBI network (German Network for … Bioinformatics Infrastructure). The work of the center is guided by the FAIR principles for scientific data management and stewardship. FAIR stands for the four foundational principles Findability, Accessibility, Interoperability, and Reusability which were established to enhance the ability of machines to automatically find, access, exchange and use data. Within this overview paper we describe three tools (SABIO-RK, Excemplify, SEEK) that exemplify the contribution of de.NBI-SysBio services to FAIR data, models, and experimental methods storage and exchange. The interconnectivity of the tools and the data workflow within systems biology projects will be explained. For many years we are the German partner in the FAIRDOM initiative (http://fair-dom.org) to establish a European data and model management service facility for systems biology.

Authors: U. Wittig, M. Rey, A. Weidemann, W. Muller

Date Published: 10th Nov 2017

Publication Type: Journal

Competing G protein-coupled receptor kinases balance G protein and beta-arrestin signaling.

Abstract (Expand)

Seven-transmembrane receptors (7TMRs) are involved in nearly all aspects of chemical communications and represent major drug targets. 7TMRs transmit their signals not only via heterotrimeric G proteins … but also through beta-arrestins, whose recruitment to the activated receptor is regulated by G protein-coupled receptor kinases (GRKs). In this paper, we combined experimental approaches with computational modeling to decipher the molecular mechanisms as well as the hidden dynamics governing extracellular signal-regulated kinase (ERK) activation by the angiotensin II type 1A receptor (AT(1A)R) in human embryonic kidney (HEK)293 cells. We built an abstracted ordinary differential equations (ODE)-based model that captured the available knowledge and experimental data. We inferred the unknown parameters by simultaneously fitting experimental data generated in both control and perturbed conditions. We demonstrate that, in addition to its well-established function in the desensitization of G-protein activation, GRK2 exerts a strong negative effect on beta-arrestin-dependent signaling through its competition with GRK5 and 6 for receptor phosphorylation. Importantly, we experimentally confirmed the validity of this novel GRK2-dependent mechanism in both primary vascular smooth muscle cells naturally expressing the AT(1A)R, and HEK293 cells expressing other 7TMRs.

Authors: D. Heitzler, G. Durand, N. Gallay, A. Rizk, S. Ahn, J. Kim, J. D. Violin, L. Dupuy, C. Gauthier, V. Piketty, P. Crepieux, A. Poupon, F. Clement, F. Fages, R. J. Lefkowitz, E. Reiter

Date Published: 26th Jun 2012

Publication Type: Journal

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