Inferring viral quasispecies spectra from 454 pyrosequencing reads

<p>Abstract</p> <p>Background</p> <p>RNA viruses infecting a host usually exist as a set of closely related sequences, referred to as quasispecies. The genomic diversity of viral quasispecies is a subject of great interest, particularly for chronic infections, since it can lead to resistance to existing therapies. High-throughput sequencing is a promising approach to characterizing viral diversity, but unfortunately standard assembly software was originally designed for single genome assembly and cannot be used to simultaneously assemble and estimate the abundance of multiple closely related quasispecies sequences.</p> <p>Results</p> <p>In this paper, we introduce a new <b>Vi</b>ral <b>Sp</b>ectrum <b>A</b>ssembler (ViSpA) method for quasispecies spectrum reconstruction and compare it with the state-of-the-art ShoRAH tool on both simulated and real 454 pyrosequencing shotgun reads from HCV and HIV quasispecies. Experimental results show that ViSpA outperforms ShoRAH on simulated error-free reads, correctly assembling 10 out of 10 quasispecies and 29 sequences out of 40 quasispecies. While ShoRAH has a significant advantage over ViSpA on reads simulated with sequencing errors due to its advanced error correction algorithm, ViSpA is better at assembling the simulated reads after they have been corrected by ShoRAH. ViSpA also outperforms ShoRAH on real 454 reads. Indeed, 7 most frequent sequences reconstructed by ViSpA from a real HCV dataset are viable (do not contain internal stop codons), and the most frequent sequence was within 1% of the actual open reading frame obtained by cloning and Sanger sequencing. In contrast, only one of the sequences reconstructed by ShoRAH is viable. On a real HIV dataset, ShoRAH correctly inferred only 2 quasispecies sequences with at most 4 mismatches whereas ViSpA correctly reconstructed 5 quasispecies with at most 2 mismatches, and 2 out of 5 sequences were inferred without any mismatches. ViSpA source code is available at <url>http://alla.cs.gsu.edu/~software/VISPA/vispa.html</url>.</p> <p>Conclusions</p> <p>ViSpA enables accurate viral quasispecies spectrum reconstruction from 454 pyrosequencing reads. We are currently exploring extensions applicable to the analysis of high-throughput sequencing data from bacterial metagenomic samples and ecological samples of eukaryote populations.</p

DNA methylation at an enhancer of the three prime repair exonuclease 2 gene (TREX2) is linked to gene expression and survival in laryngeal cancer

Background: Genetic aberrations in DNA repair genes are linked to cancer, but less is reported about epigenetic regulation of DNA repair and functional consequences. We investigated the intragenic methylation loss at the three prime repair exonuclease 2 (TREX2) locus in laryngeal (n = 256) and colorectal cancer cases (n = 95) and in pan-cancer data from The Cancer Genome Atlas (TCGA). Results: Significant methylation loss at an intragenic site of TREX2 was a frequent trait in both patient cohorts (p = 0.016 and &lt; 0.001, respectively) and in 15 out of 22 TCGA studies. Methylation loss correlated with immunohistochemically staining for TREX2 (p &lt; 0.0001) in laryngeal tumors and improved overall survival of laryngeal cancer patients (p = 0.045). Chromatin immunoprecipitation, demethylation experiments, and reporter gene assays revealed that the region of methylation loss can function as a CCAAT/enhancer binding protein alpha (CEBPA)-responsive enhancer element regulating TREX2 expression. Conclusions: The data highlight a regulatory role of TREX2 DNA methylation for gene expression which might affect incidence and survival of laryngeal cancer. Altered TREX2 protein levels in tumors may affect drug-induced DNA damage repair and provide new tailored therapies

Tumour hypoxia causes DNA hypermethylation by reducing TET activity

Hypermethylation of the promoters of tumour suppressor genes represses transcription of these genes, conferring growth advantages to cancer cells. How these changes arise is poorly understood. Here we show that the activity of oxygen-dependent ten-eleven translocation (TET) enzymes is reduced by tumour hypoxia in human and mouse cells. TET enzymes catalyse DNA demethylation through 5-methylcytosine oxidation. This reduction in activity occurs independently of hypoxia-associated alterations in TET expression, proliferation, metabolism, hypoxia-inducible factor activity or reactive oxygen species, and depends directly on oxygen shortage. Hypoxia-induced loss of TET activity increases hypermethylation at gene promoters in vitro. In patients, tumour suppressor gene promoters are markedly more methylated in hypoxic tumour tissue, independent of proliferation, stromal cell infiltration and tumour characteristics. Our data suggest that up to half of hypermethylation events are due to hypoxia, with these events conferring a selective advantage. Accordingly, increased hypoxia in mouse breast tumours increases hypermethylation, while restoration of tumour oxygenation abrogates this effect. Tumour hypoxia therefore acts as a novel regulator of DNA methylatio

Polymer-coated compliant receivers for intact laser-induced forward transfer of thin films: experimental results and modelling

In this study, we investigate both experimentally and numerically laser-induced forward transfer (LIFT) of thin films to determine the role of a thin polymer layer coating the receiver with the aim of modifying the rate of deceleration and reduction of material stress preventing intact material transfer. A numerical model of the impact phase during LIFT shows that such a layer reduces the modelled stress. The evolution of stress within the transferred deposit and the substrate as a function of the thickness of the polymer layer, the transfer velocity and the elastic properties of the polymer are evaluated. The functionality of the polymer layer is verified experimentally by LIFT printing intact 1µm-thick bismuth telluride films and polymeric light-emitting diode pads onto a layer of 12µm-thick polydimethylsiloxane and 50-nm-thick poly(3,4-ethylenedioxythiophene) blended with poly(styrenesulfonate) (PEDOT:PSS), respectively. Furthermore, it is demonstrated experimentally that the introduction of such a compliant layer improves adhesion between the deposit and its substrate

Reply to comment by Zhao et al. on “Hydrothermal events in the Linzizong Group: Implications for Paleogene exhumation and paleoaltimetry of the southern Tibetan Plateau”

In their comment on our publication about the discovery of two hydrothermal events in the Linzizong Group (Huang et al., 2022), Zhao et al. question the reliability of our thermochronologic data and the existence of hydrothermal events experienced by these rocks. They argue that their field and microscopic observations, as well as paleomagnetic studies, indicate that the lower Linzizong volcanic rocks preserve primary igneous textures and paleomagnetic signals. In this reply, we address these issues raised by Zhao et al., provide more field evidence, and conduct additional analyses that show that their assertions are not supported. We emphasize that hydrothermal events related to magmatism and deformation have systematically induced resetting of thermochronologic, stable isotopic, and paleomagnetic records of the lower Linzizong Group in the Linzhou basin of southern Tibet

Hydrothermal events in the Linzizong Group: Implications for Paleogene exhumation and paleoaltimetry of the southern Tibetan Plateau

Knowledge of the thermal history of the Linzizong Group (69–47 Ma) within the Gangdese arc is critical for interpreting the geologic evolution and isotope-based paleoaltimetric results of the southern Lhasa terrane of the Tibetan Plateau. Here, we combine results from geochronologic and thermochronologic studies of this group (divided into Dianzhong, Nianbo, and Pana formations upsection) and the structurally overlying Qianggeren granite (∼52 Ma) in the Linzhou basin. Whole rock 40Ar/39Ar ages of volcanic rocks from the stratigraphically lower Dianzhong and Nianbo formations are ∼10 Myr younger than their corresponding zircon U-Pb ages, suggesting a thermal disturbance of the argon system. Zircon (U-Th)/He ages (ZHe, 63 dates) range from 54 to 24 Ma, and apatite (U-Th-Sm)/He ages (AHe, 43 dates) range from 27 to 4 Ma. Inverse modeling of the thermochronologic data from the Qianggeren granite indicates rapid cooling between 42 and 26 Ma, possibly induced by movement of the Gulu-Hamu thrust. Positive correlations between ZHe ages and effective uranium and other geologic observations provide evidence that the Dianzhong and Nianbo formations were heated 300 °C at 54–50 Ma, and that the entire Linzizong Group was variably heated to 130–170 °C at 42–27 Ma. These findings, together with published geochronologic and thermochronologic data, suggest that abundant 50–45 Ma zircon fission track and ZHe ages from the Gangdese arc likely reflect conductive cooling of the Gangdese arc after a ∼52 Ma magmatic flare-up episode rather than rapid regional exhumation. Areas far from Cenozoic faults and deeply incised river valleys in southern Tibet have experienced only ∼3 km of exhumation since 45 Ma, consistent with the establishment of a low-relief, plateau-like physiography by Eocene time. The (hydro)thermal events are also manifested by widespread calcite recrystallization and δ18O and Δ47 alteration in most carbonates from the Linzizong Group, which must be taken into account in past and future carbonate-based paleoaltimetric studies

Synthesis and pharmacological characterization of Disila-AM80 (Disila-tamibarotene) and Disila-AM580, silicon analogues of the RARalpha-selective retinoid agonists AM80 (Tamibarotene) and AM580.

International audienc

Hydrothermal events in the Linzizong Group: Implications for Paleogene exhumation and paleoaltimetry of the southern Tibetan Plateau

Knowledge of the thermal history of the Linzizong Group (69–47 Ma) within the Gangdese arc is critical for interpreting the geologic evolution and isotope-based paleoaltimetric results of the southern Lhasa terrane of the Tibetan Plateau. Here, we combine results from geochronologic and thermochronologic studies of this group (divided into Dianzhong, Nianbo, and Pana formations upsection) and the structurally overlying Qianggeren granite (∼52 Ma) in the Linzhou basin. Whole rock 40Ar/39Ar ages of volcanic rocks from the stratigraphically lower Dianzhong and Nianbo formations are ∼10 Myr younger than their corresponding zircon U-Pb ages, suggesting a thermal disturbance of the argon system. Zircon (U-Th)/He ages (ZHe, 63 dates) range from 54 to 24 Ma, and apatite (U-Th-Sm)/He ages (AHe, 43 dates) range from 27 to 4 Ma. Inverse modeling of the thermochronologic data from the Qianggeren granite indicates rapid cooling between 42 and 26 Ma, possibly induced by movement of the Gulu-Hamu thrust. Positive correlations between ZHe ages and effective uranium and other geologic observations provide evidence that the Dianzhong and Nianbo formations were heated 300 °C at 54–50 Ma, and that the entire Linzizong Group was variably heated to 130–170 °C at 42–27 Ma. These findings, together with published geochronologic and thermochronologic data, suggest that abundant 50–45 Ma zircon fission track and ZHe ages from the Gangdese arc likely reflect conductive cooling of the Gangdese arc after a ∼52 Ma magmatic flare-up episode rather than rapid regional exhumation. Areas far from Cenozoic faults and deeply incised river valleys in southern Tibet have experienced only ∼3 km of exhumation since 45 Ma, consistent with the establishment of a low-relief, plateau-like physiography by Eocene time. The (hydro)thermal events are also manifested by widespread calcite recrystallization and δ18O and Δ47 alteration in most carbonates from the Linzizong Group, which must be taken into account in past and future carbonate-based paleoaltimetric studies.24 month embargo; available online 2 March 2022This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]