Browsing by Subject "Genome"

Now showing 1 - 12 of 12

Open Access
The bonobo genome compared with the chimpanzee and human genomes
(2012) Prüfer, K.; Munch, K.; Hellmann I.; Akagi, K.; Miller J.R.; Walenz, B.; Koren, S.; Sutton G.; Kodira, C.; Winer, R.; Knight J.R.; Mullikin J.C.; Meader, S.J.; Ponting, C.P.; Lunter G.; Higashino, S.; Hobolth, A.; Dutheil J.; Karakoç, E.; Alkan, C.; Sajjadian, S.; Catacchio, C.R.; Ventura, M.; Marques-Bonet, T.; Eichler, E.E.; André, C.; Atencia, R.; Mugisha L.; Junhold J.; Patterson, N.; Siebauer, M.; Good J.M.; Fischer, A.; Ptak, S.E.; Lachmann, M.; Symer, D.E.; Mailund, T.; Schierup, M.H.; Andrés, A.M.; Kelso J.; Pääbo, S.
Two African apes are the closest living relatives of humans: the chimpanzee (Pan troglodytes) and the bonobo (Pan paniscus). Although they are similar in many respects, bonobos and chimpanzees differ strikingly in key social and sexual behaviours, and for some of these traits they show more similarity with humans than with each other. Here we report the sequencing and assembly of the bonobo genome to study its evolutionary relationship with the chimpanzee and human genomes. We find that more than three per cent of the human genome is more closely related to either the bonobo or the chimpanzee genome than these are to each other. These regions allow various aspects of the ancestry of the two ape species to be reconstructed. In addition, many of the regions that overlap genes may eventually help us understand the genetic basis of phenotypes that humans share with one of the two apes to the exclusion of the other. © 2012 Macmillan Publishers Limited. All rights reserved.
Open Access
Characterization of local SARS-CoV-2 isolates and pathogenicity in IFNAR−/- mice
(Elsevier, 2020) Hanifehnezhad, A.; Kehribar, Ebru Şahin; Öztop, S.; Sheraz, Ali; Kasırga, Serkan; Ergünay, K.; Önder, S.; Yılmaz, E.; Engin, D.; Oğuzoğlu, T. Ç.; Şeker, Urartu Özgür Şafak; Yılmaz, E.; Özkul, A.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently a global pandemic with unprecedented public health, economic and social impact. The development of effective mitigation strategies, therapeutics and vaccines relies on detailed genomic and biological characterization of the regional viruses. This study was carried out to isolate SARS-CoV-2 viruses circulating in Anatolia, and to investigate virus propagation in frequently-used cells and experimental animals. We obtained two SARS-CoV-2 viruses from nasopharngeal swabs of confirmed cases in Vero E6 cells, visualized the virions using atomic force and scanning electron microscopy and determined size distribution of the particles. Viral cytopathic effects on Vero E6 cells were initially observed at 72 h post-inoculation and reached 90% of the cells on the 5th day. The isolates displayed with similar infectivity titers, time course and infectious progeny yields. Genome sequencing revealed the viruses to be well-conserved, with less than 1% diversity compared to the prototype virus. The analysis of the viral genomes, along with the available 62 complete genomes from Anatolia, showed limited diversity (up to 0.2% on deduced amino acids) and no evidence of recombination. The most prominent sequence variation was observed on the spike protein, resulting in the substitution D614G, with a prevalence of 56.2%. The isolates produced non-fatal infection in the transgenic type I interferon knockout (IFNAR−/-) mice, with varying neutralizing antibody titers. Hyperemia, regional consolidation and subpleural air accumulation was observed on necropsy, with similar histopathological and immunohistochemistry findings in the lungs, heart, stomach, intestines, liver, spleen and kidneys. Peak viral loads were detected in the lungs, with virus RNA present in the kidneys, jejunum, liver, spleen and heart. In conclusion, we characterized two local isolates, investigated in vitro growth dynamics in Vero E6 cells and identified IFNAR−/− mice as a potential animal model for SARS-CoV-2 experiments.
Open Access
Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication
(Proceedings of the National Academy of Sciences, 2014-12-02) Montague, M. J.; Li, G.; Gandolfi, B.; Khan, R.; Aken, B. L.; Marques Bonet, T.; Alkan C.; Thomas, G. W. C.; Warren, W. C.; Searle, S. M. J.; Minx, M.; Hilliera, LaDeana W.; Koboldt, D. C.; Davis, B. W.; Driscoll, C. A.; Barr, C. S.; Blackistone, K.; Quilez, J.; Lorente-Galdos, B.; Marques Bonet, T.; Hahnj, M. W.; Menotti-Raymond, M.; O’Brien, S. J.; Wilson, R. K.; Lyons, L. A.; Murphy, W. J.
Little is known about the genetic changes that distinguish domestic cat populations from their wild progenitors. Here we describe a high-quality domestic cat reference genome assembly and comparative inferences made with other cat breeds, wildcats, and other mammals. Based upon these comparisons, we identified positively selected genes enriched for genes involved in lipid metabolism that underpin adaptations to a hypercarnivorous diet. We also found positive selection signals within genes underlying sensory processes, especially those affecting vision and hearing in the carnivore lineage. We observed an evolutionary tradeoff between functional olfactory and vomeronasal receptor gene repertoires in the cat and dog genomes, with an expansion of the feline chemosensory system for detecting pheromones at the expense of odorant detection. Genomic regions harboring signatures of natural selection that distinguish domestic cats from their wild congeners are enriched in neural crest-related genes associated with behavior and reward in mouse models, as predicted by the domestication syndrome hypothesis. Our description of a previously unidentified allele for the gloving pigmentation pattern found in the Birman breed supports the hypothesis that cat breeds experienced strong selection on specific mutations drawn from random bred populations. Collectively, these findings provide insight into how the process of domestication altered the ancestral wildcat genome and build a resource for future disease mapping and phylogenomic studies across all members of the Felidae.
Open Access
Copy number variation of individual cattle genomes using next-generation sequencing
(2012) Bickhart, D.M.; Hou, Y.; Schroeder, S.G.; Alkan C.; Cardone, M.F.; Matukumalli L.K.; Song J.; Schnabel, R.D.; Ventura M.; Taylor J.F.; Garcia J.F.; Van Tassell, C.P.; Sonstegard, T.S.; Eichler, E. E.; Liu G.E.
Copy number variations (CNVs) affect a wide range of phenotypic traits; however, CNVs in or near segmental duplication regions are often intractable. Using a read depth approach based on next-generation sequencing, we examined genome - wide copy number differences among five taurine (three Angus, one Holstein, and one Hereford) and one indicine (Nelore) cattle. Within mapped chromosomal sequence, we identified 1265 CNV regions comprising ∼55.6-Mbp sequence-476 of which (~38%) have not previously been reported. We validated this sequence-based CNV call set with array comparative genomic hybridization (aCGH), quantitative PCR (qPCR), and fluorescent in situ hybridization (FISH), achieving a validation rate of 82% and a false positive rate of 8%. We further estimated absolute copy numbers for genomic segments and annotated genes in each individual. Surveys of the top 25 most variable genes revealed that the Nelore individual had the lowest copy numbers in 13 cases (∼52%, χ 2 test; P-value <0.05). In contrast, genes related to pathogen- and parasite-resistance, such as CATHL4 and ULBP17, were highly duplicated in the Nelore individual relative to the taurine cattle, while genes involved in lipid transport and metabolism, including APOL3 and FABP2, were highly duplicated in the beef breeds. These CNV regions also harbor genes like BPIFA2A (BSP30A) and WC1, suggesting that some CNVs may be associated with breed-specific differences in adaptation, health, and production traits. By providing the first individualized cattle CNV and segmental duplication maps and genome-wide gene copy number estimates, we enable future CNV studies into highly duplicated regions in the cattle genome. © 2012 by Cold Spring Harbor Laboratory Press.
Open Access
Demographically-based evaluation of genomic regions under selection in domestic dogs
(Public Library of Science, 2016) Freedman, A. H.; Schweizer, R. M.; Vecchyo, D. Ortega-Del; Han, E.; Davis, B. W.; Gronau, I.; Silva, P. M.; Galaverni, M.; Fan, Z.; Marx, P.; Lorente-Galdos, B.; Ramirez, O.; Hormozdiari, F.; Alkan C.; Vilà, C.; Squire K.; Geffen, E.; Kusak, J.; Boyko, A. R.; Parker, H. G.; Lee C.; Tadigotla, V.; Siepel, A.; Bustamante, C. D.; Harkins, T. T.; Nelson, S. F.; Marques Bonet, T.; Ostrander, E. A.; Wayne, R. K.; Novembre, J.
Controlling for background demographic effects is important for accurately identifying loci that have recently undergone positive selection. To date, the effects of demography have not yet been explicitly considered when identifying loci under selection during dog domestication. To investigate positive selection on the dog lineage early in the domestication, we examined patterns of polymorphism in six canid genomes that were previously used to infer a demographic model of dog domestication. Using an inferred demographic model, we computed false discovery rates (FDR) and identified 349 outlier regions consistent with positive selection at a low FDR. The signals in the top 100 regions were frequently centered on candidate genes related to brain function and behavior, including LHFPL3, CADM2, GRIK3, SH3GL2, MBP, PDE7B, NTAN1, and GLRA1. These regions contained significant enrichments in behavioral ontology categories. The 3rdtop hit, CCRN4L, plays a major role in lipid metabolism, that is supported by additional metabolism related candidates revealed in our scan, including SCP2D1 and PDXC1. Comparing our method to an empirical outlier approach that does not directly account for demography, we found only modest overlaps between the two methods, with 60% of empirical outliers having no overlap with our demography-based outlier detection approach. Demography-aware approaches have lower-rates of false discovery. Our top candidates for selection, in addition to expanding the set of neurobehavioral candidate genes, include genes related to lipid metabolism, suggesting a dietary target of selection that was important during the period when proto-dogs hunted and fed alongside hunter-gatherers. © 2016, Public Library of Science. All Rights Reserved.
Open Access
The genome sequencing of an albino Western lowland gorilla reveals inbreeding in the wild
(BioMed Central Ltd., 2013-05-31) Prado-Martinez, J.; Hernando-Herraez, I.; Lorente-Galdos, B.; Dabad, M.; Ramirez, O.; Baeza-Delgado, C.; Morcillo-Suarez, C.; Alkan C.; Hormozdiari, F.; Raineri, E.; Estellé, J.; Fernandez-Callejo, M.; Valles, M.; Ritscher, L.; Schöneberg, T.; Calle-Mustienes, Elisa de la; Casillas, S.; Rubio-Acero, R.; Melé, M.; Engelken, J.; Caceres, M.; Gomez-Skarmeta, L. L.; Gut, M.; Bertranpetit, J.; Gut, I. G.; Abello, T.; Eichler, E. E.; Mingarro, I.; Lalueza-Fox, C.; Navarro, A.; Marques Bonet, T.
Background: The only known albino gorilla, named Snowflake, was a male wild born individual from Equatorial Guinea who lived at the Barcelona Zoo for almost 40 years. He was diagnosed with non-syndromic oculocutaneous albinism, i.e. white hair, light eyes, pink skin, photophobia and reduced visual acuity. Despite previous efforts to explain the genetic cause, this is still unknown. Here, we study the genetic cause of his albinism and making use of whole genome sequencing data we find a higher inbreeding coefficient compared to other gorillas. Results: We successfully identified the causal genetic variant for Snowflake’s albinism, a non-synonymous single nucleotide variant located in a transmembrane region of SLC45A2. This transporter is known to be involved in oculocutaneous albinism type 4 (OCA4) in humans. We provide experimental evidence that shows that this amino acid replacement alters the membrane spanning capability of this transmembrane region. Finally, we provide a comprehensive study of genome-wide patterns of autozygogosity revealing that Snowflake’s parents were related, being this the first report of inbreeding in a wild born Western lowland gorilla. Conclusions: In this study we demonstrate how the use of whole genome sequencing can be extended to link genotype and phenotype in non-model organisms and it can be a powerful tool in conservation genetics (e.g., inbreeding and genetic diversity) with the expected decrease in sequencing cost.
Open Access
A global reference for human genetic variation
(Nature Publishing Group, 2015) Auton, A.; Abecasis, G. R.; Altshuler, D. M.; Durbin, R. M.; Bentley, D. R.; Chakravarti, A.; Clark, A. G.; Donnelly, P.; Eichler, E. E.; Flicek, P.; Gabriel, S. B.; Gibbs, R. A.; Green, E. D.; Hurles, M. E.; Knoppers, B. M.; Korbel, J. O.; Lander, E. S.; Lee, C.; Lehrach, H.; Mardis, E. R.; Marth, G. T.; McVean, G. A.; Nickerson, D. A.; Schmidt, J. P.; Sherry, S. T.; Wang, J.; Wilson, R. K.; Boerwinkle, E.; Doddapaneni, H.; Han, Y.; Korchina, V.; Kovar, C.; Lee, S.; Muzny, D.; Reid, J. G.; Zhu, Y.; Chang, Y.; Feng, Q.; Fang, X.; Guo, X.; Jian, M.; Jiang, H.; Jin, X.; Lan, T.; Li, G.; Li, J.; Li, Y.; Liu, S.; Liu, X.; Lu, Y.; Ma, X.; Tang, M.; Wang, B.; Wang, G.; Wu, H.; Wu, R.; Xu, X.; Yin, Y.; Zhang, D.; Zhang, W.; Zhao, J.; Zhao, M.; Zheng, X.; Gupta, N.; Gharani, N.; Toji, L. H.; Gerry, N. P.; Resch, A. M.; Barker, J.; Clarke, L.; Gil, L.; Hunt, S. E.; Kelman, G.; Kulesha, E.; Leinonen, R.; McLaren, W. M.; Radhakrishnan, R.; Roa, A.; Smirnov, D.; Smith, R. E.; Streeter, I.; Thormann, A.; Toneva, I.; Vaughan, B.; Zheng-Bradley, X.; Grocock, R.; Humphray, S.; James, T.; Kingsbury, Z.; Sudbrak, R.; Albrecht, M. W.; Amstislavskiy, V. S.; Borodina, T. A.; Lienhard, M.; Mertes, F.; Sultan, M.; Timmermann, B.; Yaspo, Marie-Laure; Fulton, L.; Ananiev, V.; Belaia, Z.; Beloslyudtsev, D.; Bouk, N.; Chen, C.; Church, D.; Cohen, R.; Cook, C.; Garner, J.; Hefferon, T.; Kimelman, M.; Liu, C.; Lopez, J.; Meric, P.; O'Sullivan, C.; Ostapchuk, Y.; Phan, L.; Ponomarov, S.; Schneider, V.; Shekhtman, E.; Sirotkin, K.; Slotta, D.; Zhang, H.; Balasubramaniam, S.; Burton, J.; Danecek, P.; Keane, T. M.; Kolb-Kokocinski, A.; McCarthy, S.; Stalker, J.; Quail, M.; Davies, C. J.; Gollub, J.; Webster, T.; Wong, B.; Zhan, Y.; Campbell, C. L.; Kong, Y.; Marcketta, A.; Yu, F.; Antunes, L.; Bainbridge, M.; Sabo, A.; Huang, Z.; Coin, L. J. M.; Fang, L.; Li, Q.; Li, Z.; Lin, H.; Liu, B.; Luo, R.; Shao, H.; Xie, Y.; Ye, C.; Yu, C.; Zhang, F.; Zheng, H.; Zhu, H.; Alkan, C.; Dal, E.; Kahveci, F.; Garrison, E. P.; Kural, D.; Lee, W. P.; Leong, W. F.; Stromberg, M.; Ward, A. N.; Wu, J.; Zhang, M.; Daly, M. J.; DePristo, M. A.; Handsaker, R. E.; Banks, E.; Bhatia, G.; Del Angel, G.; Genovese, G.; Li, H.; Kashin, S.; McCarroll, S. A.; Nemesh, J. C.; Poplin, R. E.; Yoon, S. C.; Lihm, J.; Makarov, V.; Gottipati, S.; Keinan, A.; Rodriguez-Flores, J. L.; Rausch, T.; Fritz, M. H.; Stütz, A. M.; Beal, K.; Datta, A.; Herrero, J.; Ritchie, G. R. S.; Zerbino, D.; Sabeti, P. C.; Shlyakhter, I.; Schaffner, S. F.; Vitti, J.; Cooper, D. N.; Ball, E. V.; Stenson, P. D.; Barnes, B.; Bauer, M.; Cheetham, R. K.; Cox, A.; Eberle, M.; Kahn, S.; Murray, L.; Peden, J.; Shaw, R.; Kenny, E. E.; Batzer, M. A.; Konkel, M. K.; Walker, J. A.; MacArthur, D. G.; Lek, M.; Herwig, R.; Ding, L.; Koboldt, D. C.; Larson, D.; Ye, K.; Gravel, S.; Swaroop, A.; Chew, E.; Lappalainen, T.; Erlich, Y.; Gymrek, M.; Willems, T. F.; Simpson, J. T.; Shriver, M. D.; Rosenfeld, J. A.; Bustamante, C. D.; Montgomery, S. B.; De La Vega, F. M.; Byrnes, J. K.; Carroll, A. W.; DeGorter, M. K.; Lacroute, P.; Maples, B. K.; Martin, A. R.; Moreno-Estrada, A.; Shringarpure, S. S.; Zakharia, F.; Halperin, E.; Baran, Y.; Cerveira, E.; Hwang, J.; Malhotra, A.; Plewczynski, D.; Radew, K.; Romanovitch, M.; Zhang, C.; Hyland, F. C. L.; Craig, D. W.; Christoforides, A.; Homer, N.; Izatt, T.; Kurdoglu, A. A.; Sinari, S. A.; Squire, K.; Xiao, C.; Sebat, J.; Antaki, D.; Gujral, M.; Noor, A.; Ye, K.; Burchard, E. G.; Hernandez, R. D.; Gignoux, C. R.; Haussler, D.; Katzman, S. J.; Kent, W. J.; Howie, B.; Ruiz-Linares, A.; Dermitzakis, E. T.; Devine, S. E.; Kang, H. M.; Kidd, J. M.; Blackwell, T.; Caron, S.; Chen, W.; Emery, S.; Fritsche, L.; Fuchsberger, C.; Jun, G.; Li, B.; Lyons, R.; Scheller, C.; Sidore, C.; Song, S.; Sliwerska, E.; Taliun, D.; Tan, A.; Welch, R.; Wing, M. K.; Zhan, X.; Awadalla, P.; Hodgkinson, A.; Li, Y.; Shi, X.; Quitadamo, A.; Lunter, G.; Marchini, J. L.; Myers, S.; Churchhouse, C.; Delaneau, O.; Gupta-Hinch, A.; Kretzschmar, W.; Iqbal, Z.; Mathieson, I.; Menelaou, A.; Rimmer, A.; Xifara, D. K.; Oleksyk, T. K.; Fu, Y.; Liu, X.; Xiong, M.; Jorde, L.; Witherspoon, D.; Xing, J.; Browning, B. L.; Browning, S. R.; Hormozdiari, F.; Sudmant, P. H.; Khurana, E.; Tyler-Smith, C.; Albers, C. A.; Ayub, Q.; Chen, Y.; Colonna, V.; Jostins, L.; Walter, K.; Xue, Y.; Gerstein, M. B.; Abyzov, A.; Balasubramanian, S.; Chen, J.; Clarke, D.; Fu, Y.; Harmanci, A. O.; Jin, M.; Lee, D.; Liu, J.; Mu, X. J.; Zhang, J.; Zhang, Y.; Hartl, C.; Shakir, K.; Degenhardt, J.; Meiers, S.; Raeder, B.; Casale, F. P.; Stegle, O.; Lameijer, E. W.; Hall, I.; Bafna, V.; Michaelson, J.; Gardner, E. J.; Mills, R. E.; Dayama, G.; Chen, K.; Fan, X.; Chong, Z.; Chen, T.; Chaisson, M. J.; Huddleston, J.; Malig, M.; Nelson, B. J.; Parrish, N. F.; Blackburne, B.; Lindsay, S. J.; Ning, Z.; Zhang, Y.; Lam, H.; Sisu, C.; Challis, D.; Evani, U. S.; Lu, J.; Nagaswamy, U.; Yu, J.; Li, W.; Habegger, L.; Yu, H.; Cunningham, F.; Dunham, I.; Lage, K.; Jespersen, J. B.; Horn, H.; Kim, D.; Desalle, R.; Narechania, A.; Sayres, M. A. W.; Mendez, F. L.; Poznik, G. D.; Underhill, P. A.; Mittelman, D.; Banerjee, R.; Cerezo, M.; Fitzgerald, T. W.; Louzada, S.; Massaia, A.; Yang, F.; Kalra, D.; Hale, W.; Dan, X.; Barnes, K. C.; Beiswanger, C.; Cai, H.; Cao, H.; Henn, B.; Jones, D.; Kaye, J. S.; Kent, A.; Kerasidou, A.; Mathias, R.; Ossorio, P. N.; Parker, M.; Rotimi, C. N.; Royal, C. D.; Sandoval, K.; Su, Y.; Tian, Z.; Tishkoff, S.; Via, M.; Wang, Y.; Yang, H.; Yang, L.; Zhu, J.; Bodmer, W.; Bedoya, G.; Cai, Z.; Gao, Y.; Chu, J.; Peltonen, L.; Garcia-Montero, A.; Orfao, A.; Dutil, J.; Martinez-Cruzado, J. C.; Mathias, R. A.; Hennis, A.; Watson, H.; McKenzie, C.; Qadri, F.; LaRocque, R.; Deng, X.; Asogun, D.; Folarin, O.; Happi, C.; Omoniwa, O.; Stremlau, M.; Tariyal, R.; Jallow, M.; Joof, F. S.; Corrah, T.; Rockett, K.; Kwiatkowski, D.; Kooner, J.; Hien, T. T.; Dunstan, S. J.; ThuyHang, N.; Fonnie, R.; Garry, R.; Kanneh, L.; Moses, L.; Schieffelin, J.; Grant, D. S.; Gallo, C.; Poletti, G.; Saleheen, D.; Rasheed, A.; Brooks, L. D.; Felsenfeld, A. L.; McEwen, J. E.; Vaydylevich, Y.; Duncanson, A.; Dunn, M.; Schloss, J. A.
The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies. © 2015 Macmillan Publishers Limited. All rights reserved.
Open Access
A high-coverage genome sequence from an archaic Denisovan individual
(American Association for the Advancement of Science (A A A S), 2012-10-12) Meyer, M.; Kircher, M.; Gansauge, Marie-Theres; Li, H.; Racimo, F.; Mallick, S.; Schraiber, J. G.; Jay, F.; Prüfer, K.; Filippo, Cesare de; Sudmant, P. H.; Alkan C.; Fu, Q.; Do, R.; Rohland, N.; Tandon, A.; Siebauer, M.; Green, R. E.; Bryc, K.; Briggs, A. W.; Stenzel, U.; Dabney, J.; Shendure, J.; Kitzman, J.; Hammer, M. F.; Shunkov, M. V.; Derevianko, A. P.; Patterson, N.; Andrés, A. M.; Eichler, E. E.; Slatkin, M.; Reich, D.; Kelso, J.; Pääbo, S.
We present a DNA library preparation method that has allowed us to reconstruct a high-coverage (30x) genome sequence of a Denisovan, an extinct relative of Neandertals. The quality of this genome allows a direct estimation of Denisovan heterozygosity indicating that genetic diversity in these archaic hominins was extremely low. It also allows tentative dating of the specimen on the basis of "missing evolution" in its genome, detailed measurements of Denisovan and Neandertal admixture into present-day human populations, and the generation of a near-complete catalog of genetic changes that swept to high frequency in modern humans since their divergence from Denisovans.
Open Access
Inter-varietal structural variation in grapevine genomes
(Wiley-Blackwell Publishing Ltd., 2016) Cardone, M. F.; D'Addabbo, P.; Alkan C.; Bergamini, C.; Catacchio, C. R.; Anaclerio, F.; Chiatante, G.; Marra, A.; Giannuzzi, G.; Perniola, R.; Ventura M.; Antonacci, D.
Grapevine (Vitis vinifera L.) is one of the world's most important crop plants, which is of large economic value for fruit and wine production. There is much interest in identifying genomic variations and their functional effects on inter-varietal, phenotypic differences. Using an approach developed for the analysis of human and mammalian genomes, which combines high-throughput sequencing, array comparative genomic hybridization, fluorescent inï¿½situ hybridization and quantitative PCR, we created an inter-varietal atlas of structural variations and single nucleotide variants (SNVs) for the grapevine genome analyzing four economically and genetically relevant table grapevine varieties. We found 4.8 million SNVs and detected 8% of the grapevine genome to be affected by genomic variations. We identified more than 700 copy number variation (CNV) regions and more than 2000 genes subjected to CNV as potential candidates for phenotypic differences between varieties
Open Access
On genomic repeats and reproducibility
(Oxford University Press, 2016) Firtina, C.; Alkan C.
Results: Here, we present a comprehensive analysis on the reproducibility of computational characterization of genomic variants using high throughput sequencing data. We reanalyzed the same datasets twice, using the same tools with the same parameters, where we only altered the order of reads in the input (i.e. FASTQ file). Reshuffling caused the reads from repetitive regions being mapped to different locations in the second alignment, and we observed similar results when we only applied a scatter/gather approach for read mapping - without prior shuffling. Our results show that, some of the most common variation discovery algorithms do not handle the ambiguous read mappings accurately when random locations are selected. In addition, we also observed that even when the exact same alignment is used, the GATK HaplotypeCaller generates slightly different call sets, which we pinpoint to the variant filtration step. We conclude that, algorithms at each step of genomic variation discovery and characterization need to treat ambiguous mappings in a deterministic fashion to ensure full replication of results. Availability and Implementation: Code, scripts and the generated VCF files are available at DOI:10.5281/zenodo.32611.
Open Access
PATIKA: an integrated visual environment for collaborative construction and analysis of cellular pathways
(Oxford University Press, 2002-06) Demir, Emek; Babur, Özgün; Doğrusöz, Uğur; Gürsoy, Atilla; Nişancı, Gürkan; Çetin Atalay, Rengül; Öztürk, Mehmet
Motivation: Availability of the sequences of entire genomes shifts the scientific curiosity towards the identification of function of the genomes in large scale as in genome studies. In the near future, data produced about cellular processes at molecular level will accumulate with an accelerating rate as a result of proteomics studies. In this regard, it is essential to develop tools for storing, integrating, accessing, and analyzing this data effectively. Results: We define an ontology for a comprehensive representation of cellular events. The ontology presented here enables integration of fragmented or incomplete pathway information and supports manipulation and incorporation of the stored data, as well as multiple levels of abstraction. Based on this ontology, we present the architecture of an integrated environment named PATIKA (Pathway Analysis Tool for Integration and Knowledge Acquisition). PATIKA is composed of a server-side, scalable, object-oriented database and client-side editors to provide an integrated, multi-user environment for visualizing and manipulating network of cellular events. This tool features automated pathway layout, functional computation support, advanced querying and a user-friendly graphical interface. We expect that PATIKA will be a valuable tool for rapid knowledge acquisition, microarray generated large-scale data interpretation, disease gene identification, and drug development.
Open Access
PATIKA: an integrated visual environment for collaborative construction and analysis of cellular pathways
(American Society for Biochemistry and Molecular Biology(ASBMB), 2002-09) Demir, Emek; Babur, Özgün; Doğrusöz, Uğur; Gürsoy, Atilla; Nişancı, Gürkan; Çetin Atalay, Rengül; Öztürk, Mehmet