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Article ; Online: The interplay of 3D genome organization with UV-induced DNA damage and repair.

Akköse, Ümit / Adebali, Ogün

2023 Volume 299, Issue 5, Page(s) 104679

Abstract: The 3D organization of the eukaryotic genome is crucial for various cellular processes such as gene expression and epigenetic regulation, as well as for maintaining genome integrity. However, the interplay between UV-induced DNA damage and repair with ... ...

Abstract	The 3D organization of the eukaryotic genome is crucial for various cellular processes such as gene expression and epigenetic regulation, as well as for maintaining genome integrity. However, the interplay between UV-induced DNA damage and repair with the 3D structure of the genome is not well understood. Here, we used state-of-the-art Hi-C, Damage-seq, and XR-seq datasets and in silico simulations to investigate the synergistic effects of UV damage and 3D genome organization. Our findings demonstrate that the peripheral 3D organization of the genome shields the central regions of genomic DNA from UV-induced damage. Additionally, we observed that potential damage sites of pyrimidine-pyrimidone (6-4) photoproducts are more prevalent in the nucleus center, possibly indicating an evolutionary pressure against those sites at the periphery. Interestingly, we found no correlation between repair efficiency and 3D structure after 12 min of irradiation, suggesting that UV radiation alters the genome's 3D organization in a short period of time. Interestingly, however, 2 h after UV induction, we observed more efficient repair levels in the center of the nucleus relative to the periphery. These results have implications for understanding the etiology of cancer and other diseases, as the interplay between UV radiation and the 3D genome may play a role in the development of genetic mutations and genomic instability.
MeSH term(s)	DNA Damage ; DNA Repair ; Epigenesis, Genetic ; Pyrimidine Dimers/metabolism ; Ultraviolet Rays/adverse effects
Chemical Substances	Pyrimidine Dimers
Language	English
Publishing date	2023-04-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2023.104679
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Article ; Online: Boquila: NGS read simulator to eliminate read nucleotide bias in sequence analysis.

Akköse, Ümit / Adebali, Ogün

Turkish journal of biology = Turk biyoloji dergisi

2023 Volume 47, Issue 2, Page(s) 158–163

Abstract: Sequence content is heterogeneous throughout genomes. Therefore, genome-wide next-generation sequencing (NGS) reads biased towards specific nucleotide profiles are affected by the genome-wide heterogeneous nucleotide distribution. Boquila generates ... ...

Abstract	Sequence content is heterogeneous throughout genomes. Therefore, genome-wide next-generation sequencing (NGS) reads biased towards specific nucleotide profiles are affected by the genome-wide heterogeneous nucleotide distribution. Boquila generates sequences that mimic the nucleotide profile of true reads, which can be used to correct the nucleotide-based bias of genome-wide distribution of NGS reads. Boquila can be configured to generate reads from only specified regions of the reference genome. It also allows the use of input DNA sequencing to correct the bias due to the copy number variations in the genome. Boquila uses standard file formats for input and output data, and it can be easily integrated into any workflow for high-throughput sequencing applications.
Language	English
Publishing date	2023-02-21
Publishing country	Turkey
Document type	Journal Article
ZDB-ID	2046470-8
ISSN	1303-6092 ; 1303-6092
ISSN (online)	1303-6092
ISSN	1303-6092
DOI	10.55730/1300-0152.2650
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Article ; Online: Global repair is the primary nucleotide excision repair subpathway for the removal of pyrimidine-pyrimidone (6-4) damage from the Arabidopsis genome.

Kaya, Sezgi / Erdogan, Dugcar Ebrar / Sancar, Aziz / Adebali, Ogun / Oztas, Onur

Scientific reports

2024 Volume 14, Issue 1, Page(s) 3308

Abstract: Ultraviolet (UV) component of solar radiation impairs genome stability by inducing the formation of pyrimidine-pyrimidone (6-4) photoproducts [(6-4)PPs] in plant genomes. (6-4)PPs disrupt growth and development by interfering with transcription and DNA ... ...

Abstract	Ultraviolet (UV) component of solar radiation impairs genome stability by inducing the formation of pyrimidine-pyrimidone (6-4) photoproducts [(6-4)PPs] in plant genomes. (6-4)PPs disrupt growth and development by interfering with transcription and DNA replication. To resist UV stress, plants employ both photoreactivation and nucleotide excision repair that excises oligonucleotide containing (6-4)PPs through two subpathways: global and transcription-coupled excision repair (TCR). Here, we analyzed the genome-wide excision repair-mediated repair of (6-4)PPs in Arabidopsis thaliana and found that (6-4)PPs can be repaired by TCR; however, the main subpathway to remove (6-4)PPs from the genome is global repair. Our analysis showed that open chromatin genome regions are more rapidly repaired than heterochromatin regions, and the repair level peaks at the promoter, transcription start site and transcription end site of genes. Our study revealed that the repair of (6-4)PP in plants showed a distinct genome-wide repair profile compared to the repair of other major UV-induced DNA lesion called cyclobutane pyrimidine dimers (CPDs).
MeSH term(s)	DNA Repair ; Arabidopsis/genetics ; Pyrimidinones ; Excision Repair ; Pyrimidine Dimers ; DNA Damage ; Receptors, Antigen, T-Cell/genetics ; Ultraviolet Rays
Chemical Substances	Pyrimidinones ; Pyrimidine Dimers ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2024-02-08
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-53472-8
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Article ; Online: Discovering misannotated lncRNAs using deep learning training dynamics.

Nabi, Afshan / Dilekoglu, Berke / Adebali, Ogun / Tastan, Oznur

Bioinformatics (Oxford, England)

2022 Volume 39, Issue 1

Abstract: Motivation: Recent experimental evidence has shown that some long non-coding RNAs (lncRNAs) contain small open reading frames (sORFs) that are translated into functional micropeptides, suggesting that these lncRNAs are misannotated as non-coding. ... ...

Abstract	Motivation: Recent experimental evidence has shown that some long non-coding RNAs (lncRNAs) contain small open reading frames (sORFs) that are translated into functional micropeptides, suggesting that these lncRNAs are misannotated as non-coding. Current methods to detect misannotated lncRNAs rely on ribosome-profiling (Ribo-Seq) and mass-spectrometry experiments, which are cell-type dependent and expensive. Results: Here, we propose a computational method to identify possible misannotated lncRNAs from sequence information alone. Our approach first builds deep learning models to discriminate coding and non-coding transcripts and leverages these models' training dynamics to identify misannotated lncRNAs-i.e. lncRNAs with coding potential. The set of misannotated lncRNAs we identified significantly overlap with experimentally validated ones and closely resemble coding protein sequences as evidenced by significant BLAST hits. Our analysis on a subset of misannotated lncRNA candidates also shows that some ORFs they contain yield high confidence folded structures as predicted by AlphaFold2. This methodology offers promising potential for assisting experimental efforts in characterizing the hidden proteome encoded by misannotated lncRNAs and for curating better datasets for building coding potential predictors. Availability and implementation: Source code is available at https://github.com/nabiafshan/DetectingMisannotatedLncRNAs. Supplementary information: Supplementary data are available at Bioinformatics online.
MeSH term(s)	RNA, Long Noncoding/genetics ; Deep Learning ; Amino Acid Sequence ; Proteome/genetics ; Open Reading Frames ; Micropeptides
Chemical Substances	RNA, Long Noncoding ; Proteome
Language	English
Publishing date	2022-12-27
Publishing country	England
Document type	Journal Article
ZDB-ID	1422668-6
ISSN	1367-4811 ; 1367-4803
ISSN (online)	1367-4811
ISSN	1367-4803
DOI	10.1093/bioinformatics/btac821
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Article ; Online: Common and selective signal transduction mechanisms of GPCRs.

Selçuk, Berkay / Adebali, Ogün

Progress in molecular biology and translational science

2022 Volume 195, Page(s) 89–100

Abstract: G protein-coupled receptors (GPCRs) are coupled by four major subfamilies of G proteins. GPCR coupling is processed through a combination of common and selective activation mechanisms together. Common mechanisms are shared for a group of receptors. ... ...

Abstract	G protein-coupled receptors (GPCRs) are coupled by four major subfamilies of G proteins. GPCR coupling is processed through a combination of common and selective activation mechanisms together. Common mechanisms are shared for a group of receptors. Recently, researchers managed to identify shared activation pathways for the GPCRs belonging to the same subfamilies. On the other hand, selective mechanisms are responsible for the variations within activation mechanisms. Selective processes can regulate subfamily-specific interactions between the receptor and the G proteins, and intermediate receptor conformations are required to couple particular G proteins through G protein-specific activation mechanisms. Moreover, G proteins can also selectively interact with RGS (regulators of G protein signaling) proteins as well. Selective processes modulate the signaling profile of the receptor and the tissue they are present. This chapter summarizes the recent research conducted on common and selective signal transduction mechanisms within GPCRs from an evolutionary perspective.
MeSH term(s)	Humans ; RGS Proteins/metabolism ; Signal Transduction ; Receptors, G-Protein-Coupled/metabolism ; GTP-Binding Proteins/metabolism ; Carrier Proteins/metabolism
Chemical Substances	RGS Proteins ; Receptors, G-Protein-Coupled ; GTP-Binding Proteins (EC 3.6.1.-) ; Carrier Proteins
Language	English
Publishing date	2022-07-13
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2471995-X
ISSN	1878-0814 ; 0079-6603 ; 1877-1173
ISSN (online)	1878-0814
ISSN	0079-6603 ; 1877-1173
DOI	10.1016/bs.pmbts.2022.06.030
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Article ; Online: Downregulated NPAS4 in multiple brain regions is associated with major depressive disorder.

Selçuk, Berkay / Aksu, Tuana / Dereli, Onur / Adebali, Ogün

Scientific reports

2023 Volume 13, Issue 1, Page(s) 21596

Abstract: Major Depressive Disorder (MDD) is a commonly observed psychiatric disorder that affects more than 2% of the world population with a rising trend. However, disease-associated pathways and biomarkers are yet to be fully comprehended. In this study, we ... ...

Abstract	Major Depressive Disorder (MDD) is a commonly observed psychiatric disorder that affects more than 2% of the world population with a rising trend. However, disease-associated pathways and biomarkers are yet to be fully comprehended. In this study, we analyzed previously generated RNA-seq data across seven different brain regions from three distinct studies to identify differentially and co-expressed genes for patients with MDD. Differential gene expression (DGE) analysis revealed that NPAS4 is the only gene downregulated in three different brain regions. Furthermore, co-expressing gene modules responsible for glutamatergic signaling are negatively enriched in these regions. We used the results of both DGE and co-expression analyses to construct a novel MDD-associated pathway. In our model, we propose that disruption in glutamatergic signaling-related pathways might be associated with the downregulation of NPAS4 and many other immediate-early genes (IEGs) that control synaptic plasticity. In addition to DGE analysis, we identified the relative importance of KEGG pathways in discriminating MDD phenotype using a machine learning-based approach. We anticipate that our study will open doors to developing better therapeutic approaches targeting glutamatergic receptors in the treatment of MDD.
MeSH term(s)	Humans ; Brain/metabolism ; Depressive Disorder, Major/genetics ; Depressive Disorder, Major/metabolism ; Gene Regulatory Networks ; Genes, Immediate-Early ; Signal Transduction
Chemical Substances	NPAS4 protein, human
Language	English
Publishing date	2023-12-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-48646-9
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Article ; Online: Genome-wide Excision Repair Map of Cyclobutane Pyrimidine Dimers in Arabidopsis and the Roles of CSA1 and CSA2 Proteins in Transcription-coupled Repair.

Kaya, Sezgi / Adebali, Ogun / Oztas, Onur / Sancar, Aziz

Photochemistry and photobiology

2021 Volume 98, Issue 3, Page(s) 707–712

Abstract: Plants depend on light for energy production. However, the UV component in sunlight also inflicts DNA damage, mostly in the form of cyclobutane pyrimidine dimers (CPD) and (6-4) pyrimidine-pyrimidone photoproducts, which are mutagenic and lethal to the ... ...

Abstract	Plants depend on light for energy production. However, the UV component in sunlight also inflicts DNA damage, mostly in the form of cyclobutane pyrimidine dimers (CPD) and (6-4) pyrimidine-pyrimidone photoproducts, which are mutagenic and lethal to the plant cells. These lesions are repaired by blue-light-dependent photolyases and the nucleotide excision repair enzymatic systems. Here, we characterize nucleotide excision repair in Arabidopsis thaliana genome-wide and at single nucleotide resolution with special focus on transcription-coupled repair and the role of the CSA1 and CSA2 genes/proteins in dictating the efficiency and the strand preference of repair of transcribed genes. We demonstrate that CSA1 is the dominant protein in coupling repair to transcription with minor contribution from CSA2.
MeSH term(s)	Arabidopsis/genetics ; Arabidopsis/metabolism ; DNA Damage ; DNA Repair ; Deoxyribodipyrimidine Photo-Lyase/genetics ; Deoxyribodipyrimidine Photo-Lyase/metabolism ; Pyrimidine Dimers/metabolism ; Ultraviolet Rays
Chemical Substances	Pyrimidine Dimers ; Deoxyribodipyrimidine Photo-Lyase (EC 4.1.99.3)
Language	English
Publishing date	2021-10-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	123540-0
ISSN	1751-1097 ; 0031-8655
ISSN (online)	1751-1097
ISSN	0031-8655
DOI	10.1111/php.13519
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Article ; Online: Downregulated NPAS4 in multiple brain regions is associated with major depressive disorder

Berkay Selçuk / Tuana Aksu / Onur Dereli / Ogün Adebali

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 11

Abstract: Abstract Major Depressive Disorder (MDD) is a commonly observed psychiatric disorder that affects more than 2% of the world population with a rising trend. However, disease-associated pathways and biomarkers are yet to be fully comprehended. In this ... ...

Abstract	Abstract Major Depressive Disorder (MDD) is a commonly observed psychiatric disorder that affects more than 2% of the world population with a rising trend. However, disease-associated pathways and biomarkers are yet to be fully comprehended. In this study, we analyzed previously generated RNA-seq data across seven different brain regions from three distinct studies to identify differentially and co-expressed genes for patients with MDD. Differential gene expression (DGE) analysis revealed that NPAS4 is the only gene downregulated in three different brain regions. Furthermore, co-expressing gene modules responsible for glutamatergic signaling are negatively enriched in these regions. We used the results of both DGE and co-expression analyses to construct a novel MDD-associated pathway. In our model, we propose that disruption in glutamatergic signaling-related pathways might be associated with the downregulation of NPAS4 and many other immediate-early genes (IEGs) that control synaptic plasticity. In addition to DGE analysis, we identified the relative importance of KEGG pathways in discriminating MDD phenotype using a machine learning-based approach. We anticipate that our study will open doors to developing better therapeutic approaches targeting glutamatergic receptors in the treatment of MDD.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
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Article ; Online: Evolutionary association of receptor-wide amino acids with G protein-coupling selectivity in aminergic GPCRs.

Selçuk, Berkay / Erol, Ismail / Durdağı, Serdar / Adebali, Ogün

Life science alliance

2022 Volume 5, Issue 10

Abstract: G protein-coupled receptors (GPCRs) induce signal transduction pathways through coupling to four main subtypes of G proteins ( ... ...

Abstract	G protein-coupled receptors (GPCRs) induce signal transduction pathways through coupling to four main subtypes of G proteins (G
MeSH term(s)	Amino Acids ; GTP-Binding Proteins/metabolism ; Phylogeny ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction/physiology
Chemical Substances	Amino Acids ; Receptors, G-Protein-Coupled ; GTP-Binding Proteins (EC 3.6.1.-)
Language	English
Publishing date	2022-05-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2575-1077
ISSN (online)	2575-1077
DOI	10.26508/lsa.202201439
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Article ; Online: The Mutation Profile of SARS-CoV-2 Is Primarily Shaped by the Host Antiviral Defense.

Azgari, Cem / Kilinc, Zeynep / Turhan, Berk / Circi, Defne / Adebali, Ogun

Viruses

2021 Volume 13, Issue 3

Abstract: Understanding SARS-CoV-2 evolution is a fundamental effort in coping with the COVID-19 pandemic. The virus genomes have been broadly evolving due to the high number of infected hosts world-wide. Mutagenesis and selection are two inter-dependent ... ...

Abstract	Understanding SARS-CoV-2 evolution is a fundamental effort in coping with the COVID-19 pandemic. The virus genomes have been broadly evolving due to the high number of infected hosts world-wide. Mutagenesis and selection are two inter-dependent mechanisms of virus diversification. However, which mechanisms contribute to the mutation profiles of SARS-CoV-2 remain under-explored. Here, we delineate the contribution of mutagenesis and selection to the genome diversity of SARS-CoV-2 isolates. We generated a comprehensive phylogenetic tree with representative genomes. Instead of counting mutations relative to the reference genome, we identified each mutation event at the nodes of the phylogenetic tree. With this approach, we obtained the mutation events that are independent of each other and generated the mutation profile of SARS-CoV-2 genomes. The results suggest that the heterogeneous mutation patterns are mainly reflections of host (i) antiviral mechanisms that are achieved through APOBEC, ADAR, and ZAP proteins, and (ii) probable adaptation against reactive oxygen species.
MeSH term(s)	Base Sequence ; COVID-19/genetics ; COVID-19/immunology ; COVID-19/virology ; Codon/genetics ; Evolution, Molecular ; Genome, Viral ; Humans ; Mutation ; Pandemics ; Phylogeny ; SARS-CoV-2/classification ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology
Chemical Substances	Codon
Language	English
Publishing date	2021-03-02
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13030394
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