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Article ; Online: Repeat expression is linked to patient survival and exhibits single nucleotide variation in pancreatic cancer revealing LTR70:r.879A>G.

Yandım, Cihangir / Karakülah, Gökhan

2022 Volume 822, Page(s) 146344

Abstract: Despite an overwhelming number of cancer literature reporting the links between patient survival and the expression levels of genes or mutations/single nucleotide variations (SNVs) on them, there is only limited information on repeat elements, which make ...

Abstract	Despite an overwhelming number of cancer literature reporting the links between patient survival and the expression levels of genes or mutations/single nucleotide variations (SNVs) on them, there is only limited information on repeat elements, which make at least half the human genome. Here, we analysed RNA-seq data obtained from primary pancreatic cancer tissues of 51 patients and revealed that two transposons, HERVI-int and X6A_LINE, showed an upregulation trend in the patients who lived shorter, along with 56 other potential repeats which were linked to survival. We also detected expressed single nucleotide variations (SNVs) on repeats, among which LTR70:r.879A>G stands out with the effect of its presence on this particular repeat's expression levels and a significant link to overall patient survival. Interestingly, the expression of LTR70:r.879A>G correlated with different cancer genes in comparison to its reference version highlighting the involvement of BRAF and Fumerate Hydratase with this expressed SNV. This is one of the first studies revealing possible links between repeat expression and survival in cancer and it warrants further research in this avenue.
MeSH term(s)	DNA Transposable Elements ; Databases, Genetic ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Humans ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/mortality ; Polymorphism, Single Nucleotide ; RNA-Seq ; Sequence Analysis, RNA/methods ; Up-Regulation
Chemical Substances	DNA Transposable Elements
Language	English
Publishing date	2022-02-17
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	391792-7
ISSN	1879-0038 ; 0378-1119
ISSN (online)	1879-0038
ISSN	0378-1119
DOI	10.1016/j.gene.2022.146344
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Article: Repeat expression is linked to patient survival and exhibits single nucleotide variation in pancreatic cancer revealing LTR70:r.879A>G

Yandım, Cihangir / Karakülah, Gökhan

Gene. 2022 May 15, v. 822

2022

Abstract	Despite an overwhelming number of cancer literature reporting the links between patient survival and the expression levels of genes or mutations/single nucleotide variations (SNVs) on them, there is only limited information on repeat elements, which make at least half the human genome. Here, we analysed RNA-seq data obtained from primary pancreatic cancer tissues of 51 patients and revealed that two transposons, HERVI-int and X6A_LINE, showed an upregulation trend in the patients who lived shorter, along with 56 other potential repeats which were linked to survival. We also detected expressed single nucleotide variations (SNVs) on repeats, among which LTR70:r.879A>G stands out with the effect of its presence on this particular repeat’s expression levels and a significant link to overall patient survival. Interestingly, the expression of LTR70:r.879A>G correlated with different cancer genes in comparison to its reference version highlighting the involvement of BRAF and Fumerate Hydratase with this expressed SNV. This is one of the first studies revealing possible links between repeat expression and survival in cancer and it warrants further research in this avenue.
Keywords	genes ; genetic variation ; humans ; pancreatic neoplasms ; patients ; sequence analysis ; transposons
Language	English
Dates of publication	2022-0515
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	391792-7
ISSN	1879-0038 ; 0378-1119
ISSN (online)	1879-0038
ISSN	0378-1119
DOI	10.1016/j.gene.2022.146344
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Article ; Online: Discovery and Annotation of Plant Endogenous Target Mimicry Sequences from Public Transcriptome Libraries: A Case Study of Prunus persica.

Karakülah, Gökhan

Journal of integrative bioinformatics

2017 Volume 14, Issue 4

Abstract: Novel transcript discovery through RNA sequencing has substantially improved our understanding of the transcriptome dynamics of biological systems. Endogenous target mimicry (eTM) transcripts, a novel class of regulatory molecules, bind to their target ... ...

Abstract	Novel transcript discovery through RNA sequencing has substantially improved our understanding of the transcriptome dynamics of biological systems. Endogenous target mimicry (eTM) transcripts, a novel class of regulatory molecules, bind to their target microRNAs (miRNAs) by base pairing and block their biological activity. The objective of this study was to provide a computational analysis framework for the prediction of putative eTM sequences in plants, and as an example, to discover previously un-annotated eTMs in Prunus persica (peach) transcriptome. Therefore, two public peach transcriptome libraries downloaded from Sequence Read Archive (SRA) and a previously published set of long non-coding RNAs (lncRNAs) were investigated with multi-step analysis pipeline, and 44 putative eTMs were found. Additionally, an eTM-miRNA-mRNA regulatory network module associated with peach fruit organ development was built via integration of the miRNA target information and predicted eTM-miRNA interactions. My findings suggest that one of the most widely expressed miRNA families among diverse plant species, miR156, might be potentially sponged by seven putative eTMs. Besides, the study indicates eTMs potentially play roles in the regulation of development processes in peach fruit via targeting specific miRNAs. In conclusion, by following the step-by step instructions provided in this study, novel eTMs can be identified and annotated effectively in public plant transcriptome libraries.
MeSH term(s)	Base Sequence ; Gene Library ; Gene Regulatory Networks ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Molecular Sequence Annotation ; Prunus persica/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Transcriptome/genetics
Chemical Substances	MicroRNAs ; RNA, Messenger
Language	English
Publishing date	2017-06-28
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2147212-9
ISSN	1613-4516 ; 1432-4385
ISSN (online)	1613-4516
ISSN	1432-4385
DOI	10.1515/jib-2017-0009
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Article ; Online: "In the light of evolution:" keratins as exceptional tumor biomarkers.

Takan, Işıl / Karakülah, Gökhan / Louka, Aikaterini / Pavlopoulou, Athanasia

PeerJ

2023 Volume 11, Page(s) e15099

Abstract: Keratins (KRTs) are the intermediate filament-forming proteins of epithelial cells, classified, according to their physicochemical properties, into "soft" and "hard" keratins. They have a key role in several aspects of cancer pathophysiology, including ... ...

Abstract	Keratins (KRTs) are the intermediate filament-forming proteins of epithelial cells, classified, according to their physicochemical properties, into "soft" and "hard" keratins. They have a key role in several aspects of cancer pathophysiology, including cancer cell invasion and metastasis, and several members of the KRT family serve as diagnostic or prognostic markers. The human genome contains both, functional
MeSH term(s)	Humans ; Keratins/genetics ; Phylogeny ; Biomarkers, Tumor/genetics ; Intermediate Filament Proteins/genetics ; Biological Evolution
Chemical Substances	Keratins (68238-35-7) ; Biomarkers, Tumor ; Intermediate Filament Proteins
Language	English
Publishing date	2023-03-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2703241-3
ISSN	2167-8359 ; 2167-8359
ISSN (online)	2167-8359
ISSN	2167-8359
DOI	10.7717/peerj.15099
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Article ; Online: StemnesScoRe: an R package to estimate the stemness of glioma cancer cells at single-cell resolution.

Koçhan, Necla / Oktay, Yavuz / Karakülah, Gökhan

Turkish journal of biology = Turk biyoloji dergisi

2023 Volume 47, Issue 6, Page(s) 383–392

Abstract: Background/aim: Glioblastoma is the most heterogeneous and the most difficult-to-treat type of brain tumor and one of the deadliest among all cancers. The high plasticity of glioma cancer stem cells and the resistance they develop against multiple ... ...

Abstract	Background/aim: Glioblastoma is the most heterogeneous and the most difficult-to-treat type of brain tumor and one of the deadliest among all cancers. The high plasticity of glioma cancer stem cells and the resistance they develop against multiple modalities of therapy, along with their high heterogeneity, are the main challenges faced during treatment of glioblastoma. Therefore, a better understanding of the stemness characteristics of glioblastoma cells is needed. With the development of various single-cell technologies and increasing applications of machine learning, indices based on transcriptomic and/or epigenomic data have been developed to quantitatively measure cellular states and stemness. In this study, we aimed to develop a glioma-specific stemness score model using scATAC-seq data for the first time. Materials and methods: We first applied three powerful machine-learning algorithms, i.e. random forest, gradient boosting, and extreme gradient boosting, to glioblastoma scRNA-seq data to discover the most important genes associated with cellular states. We then identified promoter and enhancer regions associated with these genes. After downloading the scATAC-seq peaks and their read counts for each patient, we identified the overlapping regions between the single-cell peaks and the peaks of genes obtained through machine-learning algorithms. Then we calculated read counts that were mapped to these overlapping regions. We finally developed a model capable of estimating the stemness score for each glioma cell using overlapping regions and the importance of genes predictive of glioblastoma cellular states. We also created an R package, accessible to all researchers regardless of their coding proficiency. Results: Our results showed that mesenchymal-like stem cells display higher stemness scores compared to neural-progenitor-, oligodendrocyte-progenitor-, and astrocyte-like cells. Conclusion: scATAC-seq can be used to assess heterogeneity in glioblastoma and identify cells with high stemness characteristics. The package is publicly available at https://github.com/Necla/StemnesScoRe and includes documentation with implementation of a real-data experiment.
Language	English
Publishing date	2023-12-15
Publishing country	Turkey
Document type	Journal Article
ZDB-ID	2046470-8
ISSN	1303-6092 ; 1303-6092
ISSN (online)	1303-6092
ISSN	1303-6092
DOI	10.55730/1300-0152.2672
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Article ; Online: PlanTEnrichment: A How-to Guide on Rapid Identification of Transposable Elements Associated with Regions of Interest in Select Plant Genomes.

Eskier, Doğa / Arıbaş, Alirıza / Karakülah, Gökhan

Methods in molecular biology (Clifton, N.J.)

2023 Volume 2703, Page(s) 59–70

Abstract: Transposable elements (TEs) are repeat elements that can relocate or create novel copies of themselves in the genome and contribute to genomic complexity and expansion, via events such as chromosome recombination or regulation of gene expression. However, ...

Abstract	Transposable elements (TEs) are repeat elements that can relocate or create novel copies of themselves in the genome and contribute to genomic complexity and expansion, via events such as chromosome recombination or regulation of gene expression. However, given the large number of such repeats across the genome, identifying repeats of interest can be a challenge in even well-annotated genomes, especially in more complex, TE-rich plant genomes. Here, we describe a protocol for PlanTEnrichment, a database we created comprising information on 11 plant genomes to analyze stress-associated TEs using publicly available data. By selecting a genome and providing a list of genes or genomic regions whose TE associations the user wants to identify, the user can rapidly obtain TE subfamilies found near the provided regions, as well as their superfamily and class, and the enrichment values of the repeats. The results also provide the locations of individual repeat instances found, alongside the input regions or genes they are associated with, and a bar graph of the top ten most significant repeat subfamilies identified. PlanTEnrichment is freely available at http://tools.ibg.deu.edu.tr/plantenrichment/ and can be used by researchers with rudimentary or no proficiency in computational analysis of TE elements, allowing for expedience in the identification of TEs of interest and helping further our understanding of the potential contributions of TEs in plant genomes.
MeSH term(s)	Humans ; DNA Transposable Elements/genetics ; Genome, Plant ; Databases, Factual ; Genomics ; Research Personnel ; Tellurium
Chemical Substances	DNA Transposable Elements ; Tellurium (NQA0O090ZJ)
Language	English
Publishing date	2023-08-18
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-3389-2_5
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Article ; Online: RTFAdb: A database of computationally predicted associations between retrotransposons and transcription factors in the human and mouse genomes.

Karakülah, Gökhan

Genomics

2017 Volume 110, Issue 5, Page(s) 257–262

Abstract: In recent years, retrotransposons have gained increasing attention as a source of binding motifs for transcription factors (TFs). Despite the substantial roles of these mobile genetic elements in the regulation of gene expression, a comprehensive ... ...

Abstract	In recent years, retrotransposons have gained increasing attention as a source of binding motifs for transcription factors (TFs). Despite the substantial roles of these mobile genetic elements in the regulation of gene expression, a comprehensive resource enabling the investigation of retrotransposon species that are bound by TFs is still lacking. Herein, I introduce for the first time a novel database called RTFAdb, which allows exploring computationally predicted associations between retrotransposons and TFs in diverse cell lines and tissues of human and mouse. My database, using over 3.000 TF ChIP-seq binding profiles collected from human and mouse samples, makes possible searching more than 1.500 retrotransposon species in the binding sites of a total of 596 TFs. RTFAdb is freely available at http://tools.ibg.deu.edu.tr/rtfa/ and has the potential to offer novel insights into mammalian transcriptional networks by providing an additional layer of information regarding the regulatory roles of retrotransposons.
MeSH term(s)	Animals ; Databases, Genetic ; Gene Regulatory Networks ; Genome, Human ; Humans ; Mice ; Protein Binding ; Retroelements ; Software ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	Retroelements ; Transcription Factors
Language	English
Publishing date	2017-11-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	356334-0
ISSN	1089-8646 ; 0888-7543
ISSN (online)	1089-8646
ISSN	0888-7543
DOI	10.1016/j.ygeno.2017.11.002
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Article ; Online: Identification of differentially expressed genomic repeats in primary hepatocellular carcinoma and their potential links to biological processes and survival.

Karakülah, Gökhan / Yandim, Cihangir

Turkish journal of biology = Turk biyoloji dergisi

2021 Volume 45, Issue 5, Page(s) 599–612

Abstract: Hepatocellular carcinoma (HCC) is one of the deadliest cancers. Research on HCC so far primarily focused on genes and provided limited information on genomic repeats, which constitute more than half of the human genome and contribute to genomic stability. ...

Abstract	Hepatocellular carcinoma (HCC) is one of the deadliest cancers. Research on HCC so far primarily focused on genes and provided limited information on genomic repeats, which constitute more than half of the human genome and contribute to genomic stability. In line with this, repeat dysregulation was significantly shown to be pathological in various cancers and other diseases. In this study, we aimed to determine the full repeat expression profile of HCC for the first time. We utilised two independent RNA-seq datasets obtained from primary HCC tumours with matched normal tissues of 20 and 17 HCC patients, respectively. We quantified repeat expressions and analysed their differential expression. We also identified repeats that are cooperatively expressed with genes by constructing a gene coexpression network. Our results indicated that HCC tumours in both datasets harbour 24 differentially expressed repeats and even more elements were coexpressed with genes involved in various metabolic pathways. We discovered that two L1 elements (L1M3b, L1M3de) were downregulated and a handful of HERV subfamily repeats (HERV-Fc1-int, HERV3-int, HERVE_a-int, HERVK11D-int, HERVK14C-int, HERVL18-int) were upregulated with the exception of HERV1_LTRc, which was downregulated. Various LTR elements (LTR32, LTR9, LTR4, LTR52-int, LTR70) and MER elements (MER11C, MER11D, MER57C1, MER9a1, MER74C) were implicated along with few other subtypes including Charlie12, MLT2A2, Tigger15a, Tigger 17b. The only satellite repeat differentially expressed in both datasets was GSATII, whose expression was upregulated in 33 (>90%) out of 37 patients. Notably, GSATII expression correlated with HCC survival genes. Elements discovered here promise future studies to be considered for biomarker and HCC therapy research. The coexpression pattern of the GSATII satellite with HCC survival genes and the fact that it has been upregulated in the vast majority of patients make this repeat particularly stand out for HCC.
Language	English
Publishing date	2021-10-18
Publishing country	Turkey
Document type	Journal Article
ZDB-ID	2046470-8
ISSN	1303-6092 ; 1300-0152
ISSN (online)	1303-6092
ISSN	1300-0152
DOI	10.3906/biy-2104-13
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Article ; Online: In Silico Identification of Stress-Associated Transposable Elements in Arabidopsis thaliana Using Public Transcriptome Data.

Eskier, Doğa / Karakülah, Gökhan

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2250, Page(s) 15–30

Abstract: Transposable elements (TEs) have been associated with stress response in many plants, making them a key target of study. However, the high variability, genomic repeat-heavy nature, and widely noncoding character of TEs have made them difficult to study ... ...

Abstract	Transposable elements (TEs) have been associated with stress response in many plants, making them a key target of study. However, the high variability, genomic repeat-heavy nature, and widely noncoding character of TEs have made them difficult to study using non-specialized methods, whether experimental or computational. In this chapter, we introduce two computational workflows to analyze transposable elements using publicly available transcriptome data. In the first of these methods, we identify TEs, which show differential expression under salt stress using sample transcriptome libraries that includes noncoding transcripts. In the second, we identify protein-coding genes with differential expression under the same conditions, and determine which TEs are enriched in the promoter regions of these stress-related genes.
MeSH term(s)	Arabidopsis/genetics ; Computational Biology/methods ; Computer Simulation ; DNA Transposable Elements ; Databases, Genetic ; Gene Expression Profiling/methods ; Gene Expression Regulation, Plant ; Molecular Sequence Annotation ; Salt Stress ; Sequence Analysis, RNA ; Transcriptome
Chemical Substances	DNA Transposable Elements
Language	English
Publishing date	2021-04-26
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1134-0_2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: RTFAdb: A database of computationally predicted associations between retrotransposons and transcription factors in the human and mouse genomes

Karakülah, Gökhan

Genomics. 2018 Sept., v. 110, no. 5

2018

Abstract	In recent years, retrotransposons have gained increasing attention as a source of binding motifs for transcription factors (TFs). Despite the substantial roles of these mobile genetic elements in the regulation of gene expression, a comprehensive resource enabling the investigation of retrotransposon species that are bound by TFs is still lacking. Herein, I introduce for the first time a novel database called RTFAdb, which allows exploring computationally predicted associations between retrotransposons and TFs in diverse cell lines and tissues of human and mouse. My database, using over 3.000 TF ChIP-seq binding profiles collected from human and mouse samples, makes possible searching more than 1.500 retrotransposon species in the binding sites of a total of 596 TFs. RTFAdb is freely available at http://tools.ibg.deu.edu.tr/rtfa/ and has the potential to offer novel insights into mammalian transcriptional networks by providing an additional layer of information regarding the regulatory roles of retrotransposons.
Keywords	binding sites ; cell lines ; databases ; gene expression regulation ; gene regulatory networks ; genome ; humans ; mice ; retrotransposons ; transcription (genetics) ; transcription factors
Language	English
Dates of publication	2018-09
Size	p. 257-262.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	356334-0
ISSN	1089-8646 ; 0888-7543
ISSN (online)	1089-8646
ISSN	0888-7543
DOI	10.1016/j.ygeno.2017.11.002
Database	NAL-Catalogue (AGRICOLA)

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