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Article ; Online: Analysis of Nucleotide Variations in Human G-Quadruplex Forming Regions Associated with Disease States.

Neupane, Aryan / Chariker, Julia H / Rouchka, Eric C

2023 Volume 14, Issue 12

Abstract: While the role of G quadruplex (G4) structures has been identified in cancers and metabolic disorders, single nucleotide variations (SNVs) and their effect on G4s in disease contexts have not been extensively studied. The COSMIC and CLINVAR databases ... ...

Abstract	While the role of G quadruplex (G4) structures has been identified in cancers and metabolic disorders, single nucleotide variations (SNVs) and their effect on G4s in disease contexts have not been extensively studied. The COSMIC and CLINVAR databases were used to detect SNVs present in G4s to identify sequence level changes and their effect on the alteration of the G4 secondary structure. A total of 37,515 G4 SNVs in the COSMIC database and 2378 in CLINVAR were identified. Of those, 7236 COSMIC (19.3%) and 457 (19%) of the CLINVAR variants result in G4 loss, while 2728 (COSMIC) and 129 (CLINVAR) SNVs gain a G4 structure. The remaining variants potentially affect the folding energy without affecting the presence of a G4. Analysis of mutational patterns in the G4 structure shows a higher selective pressure (3-fold) in the coding region on the template strand compared to the reverse strand. At the same time, an equal proportion of SNVs were observed among intronic, promoter, and enhancer regions across strands.
MeSH term(s)	Humans ; Nucleotides ; Mutation ; G-Quadruplexes
Chemical Substances	Nucleotides
Language	English
Publishing date	2023-11-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14122125
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Analysis of nucleotide variations in human g-quadruplex forming regions associated with disease states.

Neupane, Aryan / Chariker, Julia H / Rouchka, Eric C

bioRxiv : the preprint server for biology

2023

Abstract: While the role of G4 G quadruplex structures has been identified in cancers and metabolic disorders, single nucleotide variations (SNVs) and their effect on G4s in disease contexts have not been extensively studied. The COSMIC and CLINVAR databases were ... ...

Abstract	While the role of G4 G quadruplex structures has been identified in cancers and metabolic disorders, single nucleotide variations (SNVs) and their effect on G4s in disease contexts have not been extensively studied. The COSMIC and CLINVAR databases were used to detect SNVs present in G4s to identify sequence level changes and their effect on alteration of G4 secondary structure. 37,515 G4 SNVs in the COSMIC database and 2,115 in CLINVAR were identified. Of those, 7,236 COSMIC (19.3%) and 416 (18%) of the CLINVAR variants result in G4 loss, while 2,728 (COSMIC) and 112 (CLINVAR) SNVs gain a G4 structure. The gene ontology term "GnRH (Gonadotropin-releasing hormone) secretion" is enriched in 21 genes in this pathway that have a G4 destabilizing SNV. Analysis of mutational patterns in the G4 structure show a higher selective pressure (3-fold) in the coding region on the template strand compared to the non-template strand. At the same time, an equal proportion of SNVs were observed among intronic, promoter and enhancer regions across strands. Using GO and pathway enrichment, genes with SNVs for G4 forming propensity in the coding region are enriched for Regulation of Ras protein signal transduction and Src homology 3 (SH3) domain binding.
Language	English
Publishing date	2023-02-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.01.30.526341
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Article ; Online: Structural and Functional Classification of G-Quadruplex Families within the Human Genome.

Neupane, Aryan / Chariker, Julia H / Rouchka, Eric C

Genes

2023 Volume 14, Issue 3

Abstract: G-quadruplexes (G4s) are short secondary DNA structures located throughout genomic DNA and transcribed RNA. Although G4 structures have been shown to form in vivo, no current search tools that examine these structures based on previously identified G- ... ...

Abstract	G-quadruplexes (G4s) are short secondary DNA structures located throughout genomic DNA and transcribed RNA. Although G4 structures have been shown to form in vivo, no current search tools that examine these structures based on previously identified G-quadruplexes and filter them based on similar sequence, structure, and thermodynamic properties are known to exist. We present a framework for clustering G-quadruplex sequences into families using the CD-HIT, MeShClust, and DNACLUST methods along with a combination of Starcode and BLAST. Utilizing this framework to filter and annotate clusters, 95 families of G-quadruplex sequences were identified within the human genome. Profiles for each family were created using hidden Markov models to allow for the identification of additional family members and generate homology probability scores. The thermodynamic folding energy properties, functional annotation of genes associated with the sequences, scores from different prediction algorithms, and transcription factor binding motifs within a family were used to annotate and compare the diversity within and across clusters. The resulting set of G-quadruplex families can be used to further understand how different regions of the genome are regulated by factors targeting specific structures common to members of a specific cluster.
MeSH term(s)	Humans ; G-Quadruplexes ; Genome, Human ; DNA/genetics ; Sequence Analysis, DNA ; RNA
Chemical Substances	DNA (9007-49-2) ; RNA (63231-63-0)
Language	English
Publishing date	2023-03-04
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14030645
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Article ; Online: Exposure to Fine Particulate Matter Air Pollution Disrupts Erythrocyte Turnover.

Asplund, Haley / Dreyer, Hector H / Singhal, Richa / Rouchka, Eric C / O'Toole, Timothy E / Haberzettl, Petra / Conklin, Daniel J / Sansbury, Brian E

Circulation research

2024 Volume 134, Issue 9, Page(s) 1224–1227

MeSH term(s)	Particulate Matter/adverse effects ; Erythrocytes/metabolism ; Erythrocytes/drug effects ; Humans ; Air Pollution/adverse effects ; Male ; Air Pollutants/adverse effects ; Air Pollutants/toxicity ; Female
Chemical Substances	Particulate Matter ; Air Pollutants
Language	English
Publishing date	2024-04-25
Publishing country	United States
Document type	Research Support, Non-U.S. Gov't ; Letter ; Research Support, N.I.H., Extramural
ZDB-ID	80100-8
ISSN	1524-4571 ; 0009-7330 ; 0931-6876
ISSN (online)	1524-4571
ISSN	0009-7330 ; 0931-6876
DOI	10.1161/CIRCRESAHA.124.324411
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Article ; Online: Structural and Functional Classification of G-Quadruplex Families within the Human Genome

Neupane, Aryan / Chariker, Julia H. / Rouchka, Eric C.

Genes (Basel). 2023 Mar. 04, v. 14, no. 3

2023

Abstract	G-quadruplexes (G4s) are short secondary DNA structures located throughout genomic DNA and transcribed RNA. Although G4 structures have been shown to form in vivo, no current search tools that examine these structures based on previously identified G-quadruplexes and filter them based on similar sequence, structure, and thermodynamic properties are known to exist. We present a framework for clustering G-quadruplex sequences into families using the CD-HIT, MeShClust, and DNACLUST methods along with a combination of Starcode and BLAST. Utilizing this framework to filter and annotate clusters, 95 families of G-quadruplex sequences were identified within the human genome. Profiles for each family were created using hidden Markov models to allow for the identification of additional family members and generate homology probability scores. The thermodynamic folding energy properties, functional annotation of genes associated with the sequences, scores from different prediction algorithms, and transcription factor binding motifs within a family were used to annotate and compare the diversity within and across clusters. The resulting set of G-quadruplex families can be used to further understand how different regions of the genome are regulated by factors targeting specific structures common to members of a specific cluster.
Keywords	DNA ; RNA ; energy ; genome ; humans ; prediction ; probability ; thermodynamics ; transcription factors
Language	English
Dates of publication	2023-0304
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14030645
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: What is the functional reach of wastewater surveillance for respiratory viruses, pathogenic viruses of concern, and bacterial antibiotic resistance genes of interest?

Sokoloski, Kevin J / Holm, Rochelle H / Smith, Melissa / Ford, Easton E / Rouchka, Eric C / Smith, Ted

Human genomics

2023 Volume 17, Issue 1, Page(s) 114

Abstract: Background: Despite a clear appreciation of the impact of human pathogens on community health, efforts to understand pathogen dynamics within populations often follow a narrow-targeted approach and rely on the deployment of specific molecular probes for ...

Abstract	Background: Despite a clear appreciation of the impact of human pathogens on community health, efforts to understand pathogen dynamics within populations often follow a narrow-targeted approach and rely on the deployment of specific molecular probes for quantitative detection or rely on clinical detection and reporting. Main text: Genomic analysis of wastewater samples for the broad detection of viruses, bacteria, fungi, and antibiotic resistance genes of interest/concern is inherently difficult, and while deep sequencing of wastewater provides a wealth of information, a robust and cooperative foundation is needed to support healthier communities. In addition to furthering the capacity of high-throughput sequencing wastewater-based epidemiology to detect human pathogens in an unbiased and agnostic manner, it is critical that collaborative networks among public health agencies, researchers, and community stakeholders be fostered to prepare communities for future public health emergencies or for the next pandemic. A more inclusive public health infrastructure must be built for better data reporting where there is a global human health risk burden. Conclusions: As wastewater platforms continue to be developed and refined, high-throughput sequencing of human pathogens in wastewater samples will emerge as a gold standard for understanding community health.
MeSH term(s)	Humans ; Wastewater ; Wastewater-Based Epidemiological Monitoring ; Viruses/genetics ; Bacteria/genetics ; Drug Resistance, Microbial/genetics
Chemical Substances	Wastewater
Language	English
Publishing date	2023-12-18
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2147618-4
ISSN	1479-7364 ; 1479-7364
ISSN (online)	1479-7364
ISSN	1479-7364
DOI	10.1186/s40246-023-00563-8
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Article ; Online: Author Correction: HNRNPA2/B1 is upregulated in endocrine-resistant LCC9 breast cancer cells and alters the miRNA transcriptome when overexpressed in MCF-7 cells.

Klinge, Carolyn M / Piell, Kellianne M / Tooley, Christine Schaner / Rouchka, Eric C

Scientific reports

2021 Volume 11, Issue 1, Page(s) 9235

Language	English
Publishing date	2021-04-23
Publishing country	England
Document type	Published Erratum
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-87869-6
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Article ; Online: Variant analysis of 1,040 SARS-CoV-2 genomes.

Rouchka, Eric C / Chariker, Julia H / Chung, Donghoon

PloS one

2020 Volume 15, Issue 11, Page(s) e0241535

Abstract: The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) viral genome is an RNA virus consisting of approximately 30,000 bases. As part of testing efforts, whole genome sequencing of human isolates has resulted in over 1,600 complete genomes ... ...

Abstract	The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) viral genome is an RNA virus consisting of approximately 30,000 bases. As part of testing efforts, whole genome sequencing of human isolates has resulted in over 1,600 complete genomes publicly available from GenBank. We have performed a comparative analysis of the sequences, in order to detect common mutations within the population. Analysis of variants occurring within the assembled genomes yields 417 variants occurring in at least 1% of the completed genomes, including 229 within the 5' untranslated region (UTR), 152 within the 3'UTR, 2 within intergenic regions and 34 within coding sequences.
MeSH term(s)	3' Untranslated Regions ; 5' Untranslated Regions ; Betacoronavirus/genetics ; Genetic Linkage ; Genome, Viral ; Linkage Disequilibrium ; Lod Score ; Mutation ; SARS-CoV-2 ; Sequence Analysis, RNA ; Whole Genome Sequencing
Chemical Substances	3' Untranslated Regions ; 5' Untranslated Regions
Keywords	covid19
Language	English
Publishing date	2020-11-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0241535
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Article: Enhanced oxidative phosphorylation, re-organized intracellular signaling, and epigenetic de-silencing as revealed by oligodendrocyte translatome analysis after contusive spinal cord injury.

Forston, Michael D / Wei, George / Chariker, Julia H / Stephenson, Tyler / Andres, Kariena / Glover, Charles / Rouchka, Eric C / Whittemore, Scott R / Hetman, Michal

Research square

2023

Abstract: Reducing the loss of oligodendrocytes (OLs) is a major goal for neuroprotection after spinal cord injury (SCI). Therefore, the OL translatome was determined in Ribotag:Plp1-CreERT2 mice at 2, 10, and 42 days after moderate contusive T9 SCI. At 2 and 42 ... ...

Abstract	Reducing the loss of oligodendrocytes (OLs) is a major goal for neuroprotection after spinal cord injury (SCI). Therefore, the OL translatome was determined in Ribotag:Plp1-CreERT2 mice at 2, 10, and 42 days after moderate contusive T9 SCI. At 2 and 42 days, mitochondrial respiration- or actin cytoskeleton/cell junction/cell adhesion mRNAs were upregulated or downregulated, respectively. The latter effect suggests myelin sheath loss/morphological simplification which is consistent with downregulation of cholesterol biosynthesis transcripts on days 10 and 42. Various regulators of pro-survival-, cell death-, and/or oxidative stress response pathways showed peak expression acutely, on day 2. Many acutely upregulated OL genes are part of the repressive SUZ12/PRC2 operon suggesting that epigenetic de-silencing contributes to SCI effects on OL gene expression. Acute OL upregulation of the iron oxidoreductase
Language	English
Publishing date	2023-07-28
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-3164618/v1
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Article ; Online: Reactive myelopoiesis and FX-expressing macrophages triggered by chemotherapy promote cancer lung metastasis.

Wu, Caijun / Zhong, Qian / Shrestha, Rejeena / Wang, Jingzhi / Hu, Xiaoling / Li, Hong / Rouchka, Eric C / Yan, Jun / Ding, Chuanlin

JCI insight

2023 Volume 8, Issue 9

Abstract: Several preclinical studies have demonstrated that certain cytotoxic drugs enhance metastasis, but the importance of host responses triggered by chemotherapy in regulating cancer metastasis has not been fully explored. Here, we showed that multidose ... ...

Abstract	Several preclinical studies have demonstrated that certain cytotoxic drugs enhance metastasis, but the importance of host responses triggered by chemotherapy in regulating cancer metastasis has not been fully explored. Here, we showed that multidose gemcitabine (GEM) treatment promoted breast cancer lung metastasis in a transgenic spontaneous breast cancer model. GEM treatment significantly increased accumulation of CCR2+ macrophages and monocytes in the lungs of tumor-bearing as well as tumor-free mice. These changes were largely caused by chemotherapy-induced reactive myelopoiesis biased toward monocyte development. Mechanistically, enhanced production of mitochondrial ROS was observed in GEM-treated BM Lin-Sca1+c-Kit+ cells and monocytes. Treatment with the mitochondria targeted antioxidant abrogated GEM-induced hyperdifferentiation of BM progenitors. In addition, GEM treatment induced upregulation of host cell-derived CCL2, and knockout of CCR2 signaling abrogated the pro-metastatic host response induced by chemotherapy. Furthermore, chemotherapy treatment resulted in the upregulation of coagulation factor X (FX) in lung interstitial macrophages. Targeting activated FX (FXa) using FXa inhibitor or F10 gene knockdown reduced the pro-metastatic effect of chemotherapy. Together, these studies suggest a potentially novel mechanism for chemotherapy-induced metastasis via the host response-induced accumulation of monocytes/macrophages and interplay between coagulation and inflammation in the lungs.
MeSH term(s)	Mice ; Animals ; Factor X ; Myelopoiesis ; Macrophages/pathology ; Monocytes/pathology ; Lung Neoplasms/pathology ; Gemcitabine
Chemical Substances	Factor X (9001-29-0) ; Gemcitabine
Language	English
Publishing date	2023-05-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.167499
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