LIVIVO - Search results -

Search results

Result 1 - 10 of total 159

Search options

Book ; Online ; Thesis: Following the trail of cellular signatures

Kehl, Tim [Verfasser] / Lenhof, Hans-Peter [Akademischer Betreuer]

computational methods for the analysis of molecular high-throughput profiles

2022

Author's details	Tim Kehl ; Betreuer: Hans-Peter Lenhof
Keywords	Biowissenschaften, Biologie ; Life Science, Biology
Subject code	sg570
Language	English
Publisher	Saarländische Universitäts- und Landesbibliothek
Publishing place	Saarbrücken
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Simultaneous regression and classification for drug sensitivity prediction using an advanced random forest method.

Lenhof, Kerstin / Eckhart, Lea / Gerstner, Nico / Kehl, Tim / Lenhof, Hans-Peter

Scientific reports

2022 Volume 12, Issue 1, Page(s) 13458

Abstract: Machine learning methods trained on cancer cell line panels are intensively studied for the prediction of optimal anti-cancer therapies. While classification approaches distinguish effective from ineffective drugs, regression approaches aim to quantify ... ...

Abstract	Machine learning methods trained on cancer cell line panels are intensively studied for the prediction of optimal anti-cancer therapies. While classification approaches distinguish effective from ineffective drugs, regression approaches aim to quantify the degree of drug effectiveness. However, the high specificity of most anti-cancer drugs induces a skewed distribution of drug response values in favor of the more drug-resistant cell lines, negatively affecting the classification performance (class imbalance) and regression performance (regression imbalance) for the sensitive cell lines. Here, we present a novel approach called SimultAneoUs Regression and classificatiON Random Forests (SAURON-RF) based on the idea of performing a joint regression and classification analysis. We demonstrate that SAURON-RF improves the classification and regression performance for the sensitive cell lines at the expense of a moderate loss for the resistant ones. Furthermore, our results show that simultaneous classification and regression can be superior to regression or classification alone.
MeSH term(s)	Machine Learning
Language	English
Publishing date	2022-08-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-17609-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: MERIDA: a novel Boolean logic-based integer linear program for personalized cancer therapy.

Lenhof, Kerstin / Gerstner, Nico / Kehl, Tim / Eckhart, Lea / Schneider, Lara / Lenhof, Hans-Peter

Bioinformatics (Oxford, England)

2021 Volume 37, Issue 21, Page(s) 3881–3888

Abstract: Motivation: A major goal of personalized medicine in oncology is the optimization of treatment strategies given measurements of the genetic and molecular profiles of cancer cells. To further our knowledge on drug sensitivity, machine learning techniques ...

Abstract	Motivation: A major goal of personalized medicine in oncology is the optimization of treatment strategies given measurements of the genetic and molecular profiles of cancer cells. To further our knowledge on drug sensitivity, machine learning techniques are commonly applied to cancer cell line panels. Results: We present a novel integer linear programming formulation, called MEthod for Rule Identification with multi-omics DAta (MERIDA), for predicting the drug sensitivity of cancer cells. The method represents a modified version of the LOBICO method and yields easily interpretable models amenable to a Boolean logic-based interpretation. Since the proposed altered logical rules lead to an enormous acceleration of the running times of MERIDA compared to LOBICO, we cannot only consider larger input feature sets integrated from genetic and molecular omics data but also build more comprehensive models that mirror the complexity of cancer initiation and progression. Moreover, we enable the inclusion of a priori knowledge that can either stem from biomarker databases or can also be newly acquired knowledge gathered iteratively by previous runs of MERIDA. Our results show that this approach does not only lead to an improved predictive performance but also identifies a variety of putative sensitivity and resistance biomarkers. We also compare our approach to state-of-the-art machine learning methods and demonstrate the superior performance of our method. Hence, MERIDA has great potential to deepen our understanding of the molecular mechanisms causing drug sensitivity or resistance. Availability and implementation: The corresponding code is available on github (https://github.com/unisb-bioinf/MERIDA.git). Supplementary information: Supplementary data are available at Bioinformatics online.
MeSH term(s)	Humans ; Programming, Linear ; Neoplasms/genetics ; Algorithms ; Precision Medicine/methods ; Biomarkers ; Logic
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-08-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btab546
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2374: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Book ; Online ; Thesis: Multi-omics integrative analyses for decision support systems in personalized cancer treatment

Schneider, Lara Kristina [Verfasser] / Lenhof, Hans-Peter [Akademischer Betreuer]

2020

Author's details	Lara Kristina Schneider ; Betreuer: Hans-Peter Lenhof
Keywords	Naturwissenschaften ; Science
Subject code	sg500
Language	English
Publisher	Saarländische Universitäts- und Landesbibliothek
Publishing place	Saarbrücken
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Time-resolved RNA signatures of CD4+ T cells in Parkinson's disease.

Diener, Caroline / Hart, Martin / Kehl, Tim / Becker-Dorison, Anouck / Tänzer, Tanja / Schub, David / Krammes, Lena / Sester, Martina / Keller, Andreas / Unger, Marcus / Walch-Rückheim, Barbara / Lenhof, Hans-Peter / Meese, Eckart

Cell death discovery

2023 Volume 9, Issue 1, Page(s) 18

Abstract: Parkinson's disease (PD) emerges as a complex, multifactorial disease. While there is increasing evidence that dysregulated T cells play a central role in PD pathogenesis, elucidation of the pathomechanical changes in related signaling is still in its ... ...

Abstract	Parkinson's disease (PD) emerges as a complex, multifactorial disease. While there is increasing evidence that dysregulated T cells play a central role in PD pathogenesis, elucidation of the pathomechanical changes in related signaling is still in its beginnings. We employed time-resolved RNA expression upon the activation of peripheral CD4+ T cells to track and functionally relate changes on cellular signaling in representative cases of patients at different stages of PD. While only few miRNAs showed time-course related expression changes in PD, we identified groups of genes with significantly altered expression for each different time window. Towards a further understanding of the functional consequences, we highlighted pathways with decreased or increased activity in PD, including the most prominent altered IL-17 pathway. Flow cytometric analyses showed not only an increased prevalence of Th17 cells but also a specific subtype of IL-17 producing γδ-T cells, indicating a previously unknown role in PD pathogenesis.
Language	English
Publishing date	2023-01-21
Publishing country	United States
Document type	Journal Article
ISSN	2058-7716
ISSN	2058-7716
DOI	10.1038/s41420-023-01333-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: The DGCR8 E518K mutation found in Wilms tumors leads to a partial miRNA processing defect that alters gene expression patterns and biological processes.

Vardapour, Romina / Kehl, Tim / Kneitz, Susanne / Ludwig, Nicole / Meese, Eckart / Lenhof, Hans-Peter / Gessler, Manfred

Carcinogenesis

2021 Volume 43, Issue 2, Page(s) 82–93

Abstract: Wilms tumor (WT) is the most common renal tumor in childhood. We and others have previously identified oncogenic driver mutations affecting the microprocessor genes DROSHA and DGCR8 that lead to altered miRNA expression patterns. In the case of DGCR8, a ... ...

Abstract	Wilms tumor (WT) is the most common renal tumor in childhood. We and others have previously identified oncogenic driver mutations affecting the microprocessor genes DROSHA and DGCR8 that lead to altered miRNA expression patterns. In the case of DGCR8, a single recurrent hotspot mutation (E518K) was found in the RNA binding domain. To functionally assess this mutation in vitro, we generated mouse Dgcr8-KO embryonic stem cell (mESC) lines with an inducible expression of wild-type or mutant DGCR8, mirroring the hemizygous mutant expression seen in WT. RNA-seq analysis revealed significant differences of miRNA expression profiles in DGCR8-E518K compared with DGCR8-wild-type mESCs. The E518K mutation only led to a partial rescue of the reported miRNA processing defect in Dgcr8-KO, with selectively reduced expression of numerous canonical miRNAs. Nevertheless, DGCR8-E518K retained significant activity given its ability to still process many miRNAs. Subsequent to altered miRNA levels, the expression of mRNA targets was likewise changed. Functional assays showed that DGCR8-E518K cells still have a partial proliferation and differentiation defect but were able to rescue critical biological processes in embryoid body development. The stem cell program could be shut down and all three germ layers were formed. These findings suggest that the E518K mutation leads to a partial reduction of microprocessor activity and altered specificity with selective impairment only in certain developmental contexts, apparently including nephrogenesis.
MeSH term(s)	Animals ; Biological Phenomena ; Female ; Gene Expression ; Humans ; Kidney Neoplasms/genetics ; Male ; Mice ; MicroRNAs/metabolism ; Mutation ; RNA-Binding Proteins/genetics ; RNA-Binding Proteins/metabolism ; Ribonuclease III/genetics ; Wilms Tumor/genetics
Chemical Substances	DGCR8 protein, human ; Dgcr8 protein, mouse ; MicroRNAs ; RNA-Binding Proteins ; Ribonuclease III (EC 3.1.26.3)
Language	English
Publishing date	2021-12-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603134-1
ISSN	1460-2180 ; 0143-3334
ISSN (online)	1460-2180
ISSN	0143-3334
DOI	10.1093/carcin/bgab110
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1558: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: CausalTrail: Testing hypothesis using causal Bayesian networks.

Stöckel, Daniel / Schmidt, Florian / Trampert, Patrick / Lenhof, Hans-Peter

F1000Research

2015 Volume 4

Abstract: Summary Causal Bayesian Networks are a special class of Bayesian networks in which the hierarchy directly encodes the causal relationships between the variables. This allows to compute the effect of interventions, which are external changes to the system, ...

Abstract	Summary Causal Bayesian Networks are a special class of Bayesian networks in which the hierarchy directly encodes the causal relationships between the variables. This allows to compute the effect of interventions, which are external changes to the system, caused by e.g. gene knockouts or an administered drug. Whereas numerous packages for constructing causal Bayesian networks are available, hardly any program targeted at downstream analysis exists. In this paper we present CausalTrail, a tool for performing reasoning on causal Bayesian networks using the do-calculus. CausalTrail's features include multiple data import methods, a flexible query language for formulating hypotheses, as well as an intuitive graphical user interface. The program is able to account for missing data and thus can be readily applied in multi-omics settings where it is common that not all measurements are performed for all samples. Availability and Implementation CausalTrail is implemented in C++ using the Boost and Qt5 libraries. It can be obtained from https://github.com/dstoeckel/causaltrail.
Language	English
Publishing date	2015
Publishing country	England
Document type	Journal Article
ZDB-ID	2699932-8
ISSN	2046-1402 ; 2046-1402
ISSN (online)	2046-1402
ISSN	2046-1402
DOI	10.12688/f1000research.7647.1
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Full text

Order via subito

Details ▾
- Full text online
- Order with fees

Article: Changes of Protein Expression after CRISPR/Cas9 Knockout of miRNA-142 in Cell Lines Derived from Diffuse Large B-Cell Lymphoma.

Menegatti, Jennifer / Nakel, Jacqueline / Stepanov, Youli K / Caban, Karolina M / Ludwig, Nicole / Nord, Ruth / Pfitzner, Thomas / Yazdani, Maryam / Vilimova, Monika / Kehl, Tim / Lenhof, Hans-Peter / Philipp, Stephan E / Meese, Eckart / Fröhlich, Thomas / Grässer, Friedrich A / Hart, Martin

Cancers

2022 Volume 14, Issue 20

Abstract: Background: As microRNA-142 (miR-142) is the only human microRNA gene where mutations have consistently been found in about 20% of all cases of diffuse large B-cell lymphoma (DLBCL), we wanted to determine the impact of miR-142 inactivation on protein ... ...

Abstract	Background: As microRNA-142 (miR-142) is the only human microRNA gene where mutations have consistently been found in about 20% of all cases of diffuse large B-cell lymphoma (DLBCL), we wanted to determine the impact of miR-142 inactivation on protein expression of DLBCL cell lines. Methods: miR-142 was deleted by CRISPR/Cas9 knockout in cell lines from DLBCL. Results: By proteome analyses, miR-142 knockout resulted in a consistent up-regulation of 52 but also down-regulation of 41 proteins in GC-DLBCL lines BJAB and SUDHL4. Various mitochondrial ribosomal proteins were up-regulated in line with their pro-tumorigenic properties, while proteins necessary for MHC-I presentation were down-regulated in accordance with the finding that miR-142 knockout mice have a defective immune response. CFL2, CLIC4, STAU1, and TWF1 are known targets of miR-142, and we could additionally confirm AKT1S1, CCNB1, LIMA1, and TFRC as new targets of miR-142-3p or -5p. Conclusions: Seed-sequence mutants of miR-142 confirmed potential targets and novel targets of miRNAs can be identified in miRNA knockout cell lines. Due to the complex contribution of miRNAs within cellular regulatory networks, in particular when miRNAs highly present in RISC complexes are replaced by other miRNAs, primary effects on gene expression may be covered by secondary layers of regulation.
Language	English
Publishing date	2022-10-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14205031
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Wrinkle in the plan: miR-34a-5p impacts chemokine signaling by modulating CXCL10/CXCL11/CXCR3-axis in CD4

Hart, Martin / Nickl, Laura / Walch-Rueckheim, Barbara / Krammes, Lena / Rheinheimer, Stefanie / Diener, Caroline / Taenzer, Tanja / Kehl, Tim / Sester, Martina / Lenhof, Hans-Peter / Keller, Andreas / Meese, Eckart

Journal for immunotherapy of cancer

2021 Volume 8, Issue 2

Abstract: Background: In 2016 the first-in-human phase I study of a miRNA-based cancer therapy with a liposomal mimic of microRNA-34a-5p (miR-34a-5p) was closed due to five immune related serious adverse events (SAEs) resulting in four patient deaths. For future ... ...

Abstract	Background: In 2016 the first-in-human phase I study of a miRNA-based cancer therapy with a liposomal mimic of microRNA-34a-5p (miR-34a-5p) was closed due to five immune related serious adverse events (SAEs) resulting in four patient deaths. For future applications of miRNA mimics in cancer therapy it is mandatory to unravel the miRNA effects both on the tumor tissue and on immune cells. Here, we set out to analyze the impact of miR-34a-5p over-expression on the CXCL10/CXCL11/CXCR3 axis, which is central for the development of an effective cancer control. Methods: We performed a whole genome expression analysis of miR-34a-5p transfected M1 macrophages followed by an over-representation and a protein-protein network analysis. In-silico miRNA target prediction and dual luciferase assays were used for target identification and verification. Target genes involved in chemokine signaling were functionally analyzed in M1 macrophages, CD4 Results: A whole genome expression analysis of M1 macrophages with induced miR-34a-5p over-expression revealed an interaction network of downregulated target mRNAs including Conclusions: MiR-34a-5p mimic administered by intravenous administration will likely not only be up-taken by the tumor cells but also by the immune cells. Our results indicate that miR-34a-5p over-expression leads in M1 macrophages to a reduced secretion of CXCL10 and CXCL11 chemokines and in CD4
MeSH term(s)	CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Chemokine CXCL10/genetics ; Chemokine CXCL10/immunology ; Chemokine CXCL10/metabolism ; Chemokine CXCL11/genetics ; Chemokine CXCL11/immunology ; Chemokine CXCL11/metabolism ; HEK293 Cells ; Humans ; Macrophages/immunology ; MicroRNAs/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/immunology ; RNA, Messenger/metabolism ; Receptors, CXCR3/genetics ; Receptors, CXCR3/immunology ; Receptors, CXCR3/metabolism ; Signal Transduction
Chemical Substances	CXCL10 protein, human ; CXCL11 protein, human ; CXCR3 protein, human ; Chemokine CXCL10 ; Chemokine CXCL11 ; MIRN34 microRNA, human ; MicroRNAs ; RNA, Messenger ; Receptors, CXCR3
Language	English
Publishing date	2021-01-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2020-001617
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: GeneTrail: A Framework for the Analysis of High-Throughput Profiles.

Gerstner, Nico / Kehl, Tim / Lenhof, Kerstin / Eckhart, Lea / Schneider, Lara / Stöckel, Daniel / Backes, Christina / Meese, Eckart / Keller, Andreas / Lenhof, Hans-Peter

Frontiers in molecular biosciences

2021 Volume 8, Page(s) 716544

Abstract: Experimental high-throughput techniques, like next-generation sequencing or microarrays, are nowadays routinely applied to create detailed molecular profiles of cells. In general, these platforms generate high-dimensional and noisy data sets. For their ... ...

Abstract	Experimental high-throughput techniques, like next-generation sequencing or microarrays, are nowadays routinely applied to create detailed molecular profiles of cells. In general, these platforms generate high-dimensional and noisy data sets. For their analysis, powerful bioinformatics tools are required to gain novel insights into the biological processes under investigation. Here, we present an overview of the GeneTrail tool suite that offers rich functionality for the analysis and visualization of (epi-)genomic, transcriptomic, miRNomic, and proteomic profiles. Our framework enables the analysis of standard bulk, time-series, and single-cell measurements and includes various state-of-the-art methods to identify potentially deregulated biological processes and to detect driving factors within those deregulated processes. We highlight the capabilities of our web service with an analysis of a single-cell COVID-19 data set that demonstrates its potential for uncovering complex molecular mechanisms. GeneTrail can be accessed freely and without login requirements at http://genetrail.bioinf.uni-sb.de.
Language	English
Publishing date	2021-09-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2021.716544
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito