LIVIVO - Search results -

Search results

Result 1 - 10 of total 56

Search options

Article ; Online: Functional stratification of cancer drugs through integrated network similarity.

Unsal-Beyge, Seyma / Tuncbag, Nurcan

NPJ systems biology and applications

2022 Volume 8, Issue 1, Page(s) 11

Abstract: Drugs not only perturb their immediate protein targets but also modulate multiple signaling pathways. In this study, we explored networks modulated by several drugs across multiple cancer cell lines by integrating their targets with transcriptomic and ... ...

Abstract	Drugs not only perturb their immediate protein targets but also modulate multiple signaling pathways. In this study, we explored networks modulated by several drugs across multiple cancer cell lines by integrating their targets with transcriptomic and phosphoproteomic data. As a result, we obtained 236 reconstructed networks covering five cell lines and 70 drugs. A rigorous topological and pathway analysis showed that chemically and functionally different drugs may modulate overlapping networks. Additionally, we revealed a set of tumor-specific hidden pathways with the help of drug network models that are not detectable from the initial data. The difference in the target selectivity of the drugs leads to disjoint networks despite sharing a similar mechanism of action, e.g., HDAC inhibitors. We also used the reconstructed network models to study potential drug combinations based on the topological separation and found literature evidence for a set of drug pairs. Overall, network-level exploration of drug-modulated pathways and their deep comparison may potentially help optimize treatment strategies and suggest new drug combinations.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Drug Combinations ; Humans ; Neoplasms/drug therapy ; Signal Transduction ; Transcriptome
Chemical Substances	Antineoplastic Agents ; Drug Combinations
Language	English
Publishing date	2022-04-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2056-7189
ISSN (online)	2056-7189
DOI	10.1038/s41540-022-00219-8
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.

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: Editorial overview: Artificial intelligence (AI) methodologies in structural biology.

Cheng, Feixiong / Tuncbag, Nurcan

Current opinion in structural biology

2022 Volume 74, Page(s) 102387

MeSH term(s)	Artificial Intelligence ; Molecular Biology
Language	English
Publishing date	2022-05-16
Publishing country	England
Document type	Editorial ; Research Support, N.I.H., Extramural
ZDB-ID	1068353-7
ISSN	1879-033X ; 0959-440X
ISSN (online)	1879-033X
ISSN	0959-440X
DOI	10.1016/j.sbi.2022.102387
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 3206: 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

Article ; Online: Structural coverage of the human interactome.

Kosoglu, Kayra / Aydin, Zeynep / Tuncbag, Nurcan / Gursoy, Attila / Keskin, Ozlem

Briefings in bioinformatics

2024 Volume 25, Issue 1

Abstract: Complex biological processes in cells are embedded in the interactome, representing the complete set of protein-protein interactions. Mapping and analyzing the protein structures are essential to fully comprehending these processes' molecular details. ... ...

Abstract	Complex biological processes in cells are embedded in the interactome, representing the complete set of protein-protein interactions. Mapping and analyzing the protein structures are essential to fully comprehending these processes' molecular details. Therefore, knowing the structural coverage of the interactome is important to show the current limitations. Structural modeling of protein-protein interactions requires accurate protein structures. In this study, we mapped all experimental structures to the reference human proteome. Later, we found the enrichment in structural coverage when complementary methods such as homology modeling and deep learning (AlphaFold) were included. We then collected the interactions from the literature and databases to form the reference human interactome, resulting in 117 897 non-redundant interactions. When we analyzed the structural coverage of the interactome, we found that the number of experimentally determined protein complex structures is scarce, corresponding to 3.95% of all binary interactions. We also analyzed known and modeled structures to potentially construct the structural interactome with a docking method. Our analysis showed that 12.97% of the interactions from HuRI and 73.62% and 32.94% from the filtered versions of STRING and HIPPIE could potentially be modeled with high structural coverage or accuracy, respectively. Overall, this paper provides an overview of the current state of structural coverage of the human proteome and interactome.
MeSH term(s)	Humans ; Proteome ; Databases, Factual
Chemical Substances	Proteome
Language	English
Publishing date	2024-01-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2068142-2
ISSN	1477-4054 ; 1467-5463
ISSN (online)	1477-4054
ISSN	1467-5463
DOI	10.1093/bib/bbad496
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 6262: Show issues

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

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Performance Assessment of the Network Reconstruction Approaches on Various Interactomes.

Arici, M Kaan / Tuncbag, Nurcan

Frontiers in molecular biosciences

2021 Volume 8, Page(s) 666705

Abstract: Beyond the list of molecules, there is a necessity to collectively consider multiple sets of omic data and to reconstruct the connections between the molecules. Especially, pathway reconstruction is crucial to understanding disease biology because ... ...

Abstract	Beyond the list of molecules, there is a necessity to collectively consider multiple sets of omic data and to reconstruct the connections between the molecules. Especially, pathway reconstruction is crucial to understanding disease biology because abnormal cellular signaling may be pathological. The main challenge is how to integrate the data together in an accurate way. In this study, we aim to comparatively analyze the performance of a set of network reconstruction algorithms on multiple reference interactomes. We first explored several human protein interactomes, including PathwayCommons, OmniPath, HIPPIE, iRefWeb, STRING, and ConsensusPathDB. The comparison is based on the coverage of each interactome in terms of cancer driver proteins, structural information of protein interactions, and the bias toward well-studied proteins. We next used these interactomes to evaluate the performance of network reconstruction algorithms including all-pair shortest path, heat diffusion with flux, personalized PageRank with flux, and prize-collecting Steiner forest (PCSF) approaches. Each approach has its own merits and weaknesses. Among them, PCSF had the most balanced performance in terms of precision and recall scores when 28 pathways from NetPath were reconstructed using the listed algorithms. Additionally, the reference interactome affects the performance of the network reconstruction approaches. The coverage and disease- or tissue-specificity of each interactome may vary, which may result in differences in the reconstructed networks.
Language	English
Publishing date	2021-10-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2814330-9
ISSN	2296-889X
ISSN	2296-889X
DOI	10.3389/fmolb.2021.666705
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: SETD3 regulates endoderm differentiation of mouse embryonic stem cells through canonical Wnt signaling pathway.

Alganatay, Ceren / Balbasi, Emre / Tuncbag, Nurcan / Sezginmert, Dersu / Terzi Cizmecioglu, Nihal

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2024 Volume 38, Issue 4, Page(s) e23463

Abstract: With self-renewal and pluripotency features, embryonic stem cells (ESCs) provide an invaluable tool to investigate early cell fate decisions. Pluripotency exit and lineage commitment depend on precise regulation of gene expression that requires ... ...

Abstract	With self-renewal and pluripotency features, embryonic stem cells (ESCs) provide an invaluable tool to investigate early cell fate decisions. Pluripotency exit and lineage commitment depend on precise regulation of gene expression that requires coordination between transcription (TF) and chromatin factors in response to various signaling pathways. SET domain-containing 3 (SETD3) is a methyltransferase that can modify histones in the nucleus and actin in the cytoplasm. Through an shRNA screen, we previously identified SETD3 as an important factor in the meso/endodermal lineage commitment of mouse ESCs (mESC). In this study, we identified SETD3-dependent transcriptomic changes during endoderm differentiation of mESCs using time-course RNA-seq analysis. We found that SETD3 is involved in the timely activation of the endoderm-related gene network. The canonical Wnt signaling pathway was one of the markedly altered signaling pathways in the absence of SETD3. The assessment of Wnt transcriptional activity revealed a significant reduction in Setd3-deleted (setd3∆) mESCs coincident with a decrease in the nuclear pool of the key TF β-catenin level, though no change was observed in its mRNA or total protein level. Furthermore, a proximity ligation assay (PLA) found an interaction between SETD3 and β-catenin. We were able to rescue the differentiation defect by stably re-expressing SETD3 or activating the canonical Wnt signaling pathway by changing mESC culture conditions. Our results suggest that alterations in the canonical Wnt pathway activity and subcellular localization of β-catenin might contribute to the endoderm differentiation defect of setd3∆ mESCs.
MeSH term(s)	Animals ; Mice ; beta Catenin/metabolism ; Cell Differentiation/genetics ; Endoderm ; Mouse Embryonic Stem Cells ; Wnt Signaling Pathway/physiology
Chemical Substances	beta Catenin ; Setd3 protein, mouse (EC 2.1.1.-)
Language	English
Publishing date	2024-02-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.202301883R
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2266: 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)
Zs.MO 296: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Pan-cancer clinical impact of latent drivers from double mutations.

Yavuz, Bengi Ruken / Tsai, Chung-Jung / Nussinov, Ruth / Tuncbag, Nurcan

Communications biology

2023 Volume 6, Issue 1, Page(s) 202

Abstract: Here, we discover potential 'latent driver' mutations in cancer genomes. Latent drivers have low frequencies and minor observable translational potential. As such, to date they have escaped identification. Their discovery is important, since when paired ... ...

Abstract	Here, we discover potential 'latent driver' mutations in cancer genomes. Latent drivers have low frequencies and minor observable translational potential. As such, to date they have escaped identification. Their discovery is important, since when paired in cis, latent driver mutations can drive cancer. Our comprehensive statistical analysis of the pan-cancer mutation profiles of ~60,000 tumor sequences from the TCGA and AACR-GENIE cohorts identifies significantly co-occurring potential latent drivers. We observe 155 same gene double mutations of which 140 individual components are cataloged as latent drivers. Evaluation of cell lines and patient-derived xenograft response data to drug treatment indicate that in certain genes double mutations may have a prominent role in increasing oncogenic activity, hence obtaining a better drug response, as in PIK3CA. Taken together, our comprehensive analyses indicate that same-gene double mutations are exceedingly rare phenomena but are a signature for some cancer types, e.g., breast, and lung cancers. The relative rarity of doublets can be explained by the likelihood of strong signals resulting in oncogene-induced senescence, and by doublets consisting of non-identical single residue components populating the background mutational load, thus not identified.
MeSH term(s)	Humans ; Mutation ; Lung Neoplasms ; Proteomics
Language	English
Publishing date	2023-02-20
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-023-04519-5
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: Computational approaches leveraging integrated connections of multi-omic data toward clinical applications.

Demirel, Habibe Cansu / Arici, Muslum Kaan / Tuncbag, Nurcan

Molecular omics

2022 Volume 18, Issue 1, Page(s) 7–18

Abstract: In line with the advances in high-throughput technologies, multiple omic datasets have accumulated to study biological systems and diseases coherently. No single omics data type is capable of fully representing cellular activity. The complexity of the ... ...

Abstract	In line with the advances in high-throughput technologies, multiple omic datasets have accumulated to study biological systems and diseases coherently. No single omics data type is capable of fully representing cellular activity. The complexity of the biological processes arises from the interactions between omic entities such as genes, proteins, and metabolites. Therefore, multi-omic data integration is crucial but challenging. The impact of the molecular alterations in multi-omic data is not local in the neighborhood of the altered gene or protein; rather, the impact diffuses in the network and changes the functionality of multiple signaling pathways and regulation of the gene expression. Additionally, multi-omic data is high-dimensional and has background noise. Several integrative approaches have been developed to accurately interpret the multi-omic datasets, including machine learning, network-based methods, and their combination. In this review, we overview the most recent integrative approaches and tools with a focus on network-based methods. We then discuss these approaches according to their specific applications, from disease-network and biomarker identification to patient stratification, drug discovery, and repurposing.
MeSH term(s)	Genomics/methods ; Humans ; Machine Learning
Language	English
Publishing date	2022-01-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	2515-4184
ISSN (online)	2515-4184
DOI	10.1039/d1mo00158b
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: Comparative biological network analysis for differentially expressed proteins as a function of bacilysin biosynthesis in Bacillus subtilis.

Kutnu, Meltem / İşlerel, Elif Tekin / Tunçbağ, Nurcan / Özcengiz, Gülay

Integrative biology : quantitative biosciences from nano to macro

2022 Volume 14, Issue 5, Page(s) 99–110

Abstract: The Gram-positive bacterium Bacillus subtilis produces a diverse range of secondary metabolites with different structures and activities. Among them, bacilysin is an enzymatically synthesized dipeptide that consists of L-alanine and L-anticapsin. ... ...

Abstract	The Gram-positive bacterium Bacillus subtilis produces a diverse range of secondary metabolites with different structures and activities. Among them, bacilysin is an enzymatically synthesized dipeptide that consists of L-alanine and L-anticapsin. Previous research by our group has suggested bacilysin's role as a pleiotropic molecule in its producer, B. subtilis PY79. However, the nature of protein interactions in the absence of bacilysin has not been defined. In the present work, we constructed a protein-protein interaction subnetwork by using Omics Integrator based on our recent comparative proteomics data obtained from a bacilysin-silenced strain, OGU1. Functional enrichment analyses on the resulting networks pointed to certain putatively perturbed pathways such as citrate cycle, quorum sensing and secondary metabolite biosynthesis. Various molecules, which were absent from the experimental data, were included in the final network. We believe that this study can guide further experiments in the identification and confirmation of protein-protein interactions in B. subtilis.
MeSH term(s)	Bacillus subtilis ; Bacterial Proteins/metabolism ; Dipeptides/metabolism ; Quorum Sensing
Chemical Substances	Bacterial Proteins ; Dipeptides ; bacilysin (90R5Q4BW17)
Language	English
Publishing date	2022-07-28
Publishing country	England
Document type	Comparative Study ; Journal Article
ZDB-ID	2480063-6
ISSN	1757-9708 ; 1757-9694
ISSN (online)	1757-9708
ISSN	1757-9694
DOI	10.1093/intbio/zyac010
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Structural analysis of mammalian protein phosphorylation at a proteome level.

Kamacioglu, Altug / Tuncbag, Nurcan / Ozlu, Nurhan

Structure (London, England : 1993)

2021 Volume 29, Issue 11, Page(s) 1219–1229.e3

Abstract: Phosphorylation is an essential post-translational modification for almost all cellular processes. Several global phosphoproteomics analyses have revealed phosphorylation profiles under different conditions. Beyond identification of phospho-sites, ... ...

Abstract	Phosphorylation is an essential post-translational modification for almost all cellular processes. Several global phosphoproteomics analyses have revealed phosphorylation profiles under different conditions. Beyond identification of phospho-sites, protein structures add another layer of information about their functionality. In this study, we systematically characterize phospho-sites based on their 3D locations in the protein and establish a location map for phospho-sites. More than 250,000 phospho-sites have been analyzed, of which 8,686 sites match at least one structure and are stratified based on their respective 3D positions. Core phospho-sites possess two distinct groups based on their dynamicity. Dynamic core phosphorylations are significantly more functional compared with static ones. The dynamic core and the interface phospho-sites are the most functional among all 3D phosphorylation groups. Our analysis provides global characterization and stratification of phospho-sites from a structural perspective that can be utilized for predicting functional relevance and filtering out false positives in phosphoproteomic studies.
MeSH term(s)	Humans ; Phosphoproteins/metabolism ; Phosphorylation ; Protein Conformation ; Proteome/metabolism ; Proteomics
Chemical Substances	Phosphoproteins ; Proteome
Language	English
Publishing date	2021-06-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1213087-4
ISSN	1878-4186 ; 0969-2126
ISSN (online)	1878-4186
ISSN	0969-2126
DOI	10.1016/j.str.2021.06.008
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4141: 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

Article ; Online: Context dependent isoform specific PI3K inhibition confers drug resistance in hepatocellular carcinoma cells.

Narci, Kubra / Kahraman, Deniz Cansen / Koyas, Altay / Ersahin, Tulin / Tuncbag, Nurcan / Atalay, Rengul Cetin

BMC cancer

2022 Volume 22, Issue 1, Page(s) 320

Abstract: Background: Targeted therapies for Primary liver cancer (HCC) is limited to the multi-kinase inhibitors, and not fully effective due to the resistance to these agents because of the heterogeneous molecular nature of HCC developed during chronic liver ... ...

Abstract	Background: Targeted therapies for Primary liver cancer (HCC) is limited to the multi-kinase inhibitors, and not fully effective due to the resistance to these agents because of the heterogeneous molecular nature of HCC developed during chronic liver disease stages and cirrhosis. Although combinatorial therapy can increase the efficiency of targeted therapies through synergistic activities, isoform specific effects of the inhibitors are usually ignored. This study concentrated on PI3K/Akt/mTOR pathway and the differential combinatory bioactivities of isoform specific PI3K-α inhibitor (PIK-75) or PI3K-β inhibitor (TGX-221) with Sorafenib dependent on PTEN context. Methods: The bioactivities of inhibitors on PTEN adequate Huh7 and deficient Mahlavu cells were investigated with real time cell growth, cell cycle and cell migration assays. Differentially expressed genes from RNA-Seq were identified by edgeR tool. Systems level network analysis of treatment specific pathways were performed with Prize Collecting Steiner Tree (PCST) on human interactome and enriched networks were visualized with Cytoscape platform. Results: Our data from combinatory treatment of Sorafenib and PIK-75 and TGX-221 showed opposite effects; while PIK-75 displays synergistic effects on Huh7 cells leading to apoptotic cell death, Sorafenib with TGX-221 display antagonistic effects and significantly promotes cell growth in PTEN deficient Mahlavu cells. Signaling pathways were reconstructed and analyzed in-depth from RNA-Seq data to understand mechanism of differential synergistic or antagonistic effects of PI3K-α (PIK-75) and PI3K-β (TGX-221) inhibitors with Sorafenib. PCST allowed as to identify AOX1 and AGER as targets in PI3K/Akt/mTOR pathway for this combinatory effect. The siRNA knockdown of AOX1 and AGER significantly reduced cell proliferation in HCC cells. Conclusions: Simultaneously constructed and analyzed differentially expressed cellular networks presented in this study, revealed distinct consequences of isoform specific PI3K inhibition in PTEN adequate and deficient liver cancer cells. We demonstrated the importance of context dependent and isoform specific PI3K/Akt/mTOR signaling inhibition in drug resistance during combination therapies. ( https://github.com/cansyl/Isoform-spesific-PI3K-inhibitor-analysis ).
MeSH term(s)	Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/metabolism ; Cell Line, Tumor ; Drug Resistance ; Humans ; Liver Neoplasms/drug therapy ; Liver Neoplasms/genetics ; Liver Neoplasms/metabolism ; Niacinamide/therapeutic use ; Phenylurea Compounds/therapeutic use ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Isoforms/genetics ; Proto-Oncogene Proteins c-akt/metabolism
Chemical Substances	Phenylurea Compounds ; Protein Isoforms ; Niacinamide (25X51I8RD4) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2022-03-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2041352-X
ISSN	1471-2407 ; 1471-2407
ISSN (online)	1471-2407
ISSN	1471-2407
DOI	10.1186/s12885-022-09357-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

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

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

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

More links

Kategorien

Order via subito