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1. CAGI, the Critical Assessment of Genome Interpretation, establishes progress and prospects for computational genetic variant interpretation methods

Author

Jain, Shantanu, Bakolitsa, Constantina, Brenner, Steven E, Radivojac, Predrag, Moult, John, Repo, Susanna, Hoskins, Roger A, Andreoletti, Gaia, Barsky, Daniel, Chellapan, Ajithavalli, Chu, Hoyin, Dabbiru, Navya, Kollipara, Naveen K, Ly, Melissa, Neumann, Andrew J, Pal, Lipika R, Odell, Eric, Pandey, Gaurav, Peters-Petrulewicz, Robin C, Srinivasan, Rajgopal, Yee, Stephen F, Yeleswarapu, Sri Jyothsna, Zuhl, Maya, Adebali, Ogun, Patra, Ayoti, Beer, Michael A, Hosur, Raghavendra, Peng, Jian, Bernard, Brady M, Berry, Michael, Dong, Shengcheng, Boyle, Alan P, Adhikari, Aashish, Chen, Jingqi, Hu, Zhiqiang, Wang, Robert, Wang, Yaqiong, Miller, Maximilian, Wang, Yanran, Bromberg, Yana, Turina, Paola, Capriotti, Emidio, Han, James J, Ozturk, Kivilcim, Carter, Hannah, Babbi, Giulia, Bovo, Samuele, Di Lena, Pietro, Martelli, Pier Luigi, Savojardo, Castrense, Casadio, Rita, Cline, Melissa S, De Baets, Greet, Bonache, Sandra, Díez, Orland, Gutiérrez-Enríquez, Sara, Fernández, Alejandro, Montalban, Gemma, Ootes, Lars, Özkan, Selen, Padilla, Natàlia, Riera, Casandra, De la Cruz, Xavier, Diekhans, Mark, Huwe, Peter J, Wei, Qiong, Xu, Qifang, Dunbrack, Roland L, Gotea, Valer, Elnitski, Laura, Margolin, Gennady, Fariselli, Piero, Kulakovskiy, Ivan V, Makeev, Vsevolod J, Penzar, Dmitry D, Vorontsov, Ilya E, Favorov, Alexander V, Forman, Julia R, Hasenahuer, Marcia, Fornasari, Maria S, Parisi, Gustavo, Avsec, Ziga, Çelik, Muhammed H, Nguyen, Thi Yen Duong, Gagneur, Julien, Shi, Fang-Yuan, Edwards, Matthew D, Guo, Yuchun, Tian, Kevin, Zeng, Haoyang, Gifford, David K, Göke, Jonathan, Zaucha, Jan, Gough, Julian, Ritchie, Graham RS, Frankish, Adam, Mudge, Jonathan M, Harrow, Jennifer, Young, Erin L, and Yu, Yao

Subjects
Biological Sciences, Genetics, Human Genome, 2.1 Biological and endogenous factors, Good Health and Well Being, Humans, Computational Biology, Mutation, Missense, Phenotype, Critical Assessment of Genome Interpretation Consortium, Environmental Sciences, Information and Computing Sciences, Bioinformatics
Abstract

BackgroundThe Critical Assessment of Genome Interpretation (CAGI) aims to advance the state-of-the-art for computational prediction of genetic variant impact, particularly where relevant to disease. The five complete editions of the CAGI community experiment comprised 50 challenges, in which participants made blind predictions of phenotypes from genetic data, and these were evaluated by independent assessors.ResultsPerformance was particularly strong for clinical pathogenic variants, including some difficult-to-diagnose cases, and extends to interpretation of cancer-related variants. Missense variant interpretation methods were able to estimate biochemical effects with increasing accuracy. Assessment of methods for regulatory variants and complex trait disease risk was less definitive and indicates performance potentially suitable for auxiliary use in the clinic.ConclusionsResults show that while current methods are imperfect, they have major utility for research and clinical applications. Emerging methods and increasingly large, robust datasets for training and assessment promise further progress ahead.

Published
2024

2. Matching phenotypes to whole genomes: Lessons learned from four iterations of the personal genome project community challenges

Author

Cai, Binghuang, Li, Biao, Kiga, Nikki, Thusberg, Janita, Bergquist, Timothy, Chen, Yun‐Ching, Niknafs, Noushin, Carter, Hannah, Tokheim, Collin, Beleva‐Guthrie, Violeta, Douville, Christopher, Bhattacharya, Rohit, Yeo, Hui Ting Grace, Fan, Jean, Sengupta, Sohini, Kim, Dewey, Cline, Melissa, Turner, Tychele, Diekhans, Mark, Zaucha, Jan, Pal, Lipika R, Cao, Chen, Yu, Chen‐Hsin, Yin, Yizhou, Carraro, Marco, Giollo, Manuel, Ferrari, Carlo, Leonardi, Emanuela, Tosatto, Silvio CE, Bobe, Jason, Ball, Madeleine, Hoskins, Roger A, Repo, Susanna, Church, George, Brenner, Steven E, Moult, John, Gough, Julian, Stanke, Mario, Karchin, Rachel, and Mooney, Sean D

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Biotechnology, Good Health and Well Being, Area Under Curve, Genetic Predisposition to Disease, High-Throughput Nucleotide Sequencing, Human Genome Project, Humans, Phenotype, Quantitative Trait Loci, Whole Genome Sequencing, biomedical informatics, community challenge, critical assessment, genome, genome interpretation, open consent, personal genome project, phenotype, Clinical Sciences, Genetics & Heredity, Clinical sciences
Abstract

The advent of next-generation sequencing has dramatically decreased the cost for whole-genome sequencing and increased the viability for its application in research and clinical care. The Personal Genome Project (PGP) provides unrestricted access to genomes of individuals and their associated phenotypes. This resource enabled the Critical Assessment of Genome Interpretation (CAGI) to create a community challenge to assess the bioinformatics community's ability to predict traits from whole genomes. In the CAGI PGP challenge, researchers were asked to predict whether an individual had a particular trait or profile based on their whole genome. Several approaches were used to assess submissions, including ROC AUC (area under receiver operating characteristic curve), probability rankings, the number of correct predictions, and statistical significance simulations. Overall, we found that prediction of individual traits is difficult, relying on a strong knowledge of trait frequency within the general population, whereas matching genomes to trait profiles relies heavily upon a small number of common traits including ancestry, blood type, and eye color. When a rare genetic disorder is present, profiles can be matched when one or more pathogenic variants are identified. Prediction accuracy has improved substantially over the last 6 years due to improved methodology and a better understanding of features.

Published
2017

3. The Release 6 reference sequence of the Drosophila melanogaster genome

Author

Hoskins, Roger A, Carlson, Joseph W, Wan, Kenneth H, Park, Soo, Mendez, Ivonne, Galle, Samuel E, Booth, Benjamin W, Pfeiffer, Barret D, George, Reed A, Svirskas, Robert, Krzywinski, Martin, Schein, Jacqueline, Accardo, Maria Carmela, Damia, Elisabetta, Messina, Giovanni, Méndez-Lago, María, de Pablos, Beatriz, Demakova, Olga V, Andreyeva, Evgeniya N, Boldyreva, Lidiya V, Marra, Marco, Carvalho, A Bernardo, Dimitri, Patrizio, Villasante, Alfredo, Zhimulev, Igor F, Rubin, Gerald M, Karpen, Gary H, and Celniker, Susan E

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Biotechnology, 1.1 Normal biological development and functioning, Animals, Chromosome Mapping, Chromosomes, Artificial, Bacterial, Computational Biology, Contig Mapping, Drosophila melanogaster, Genome, High-Throughput Nucleotide Sequencing, In Situ Hybridization, Fluorescence, Molecular Sequence Data, Polytene Chromosomes, Restriction Mapping, Medical and Health Sciences, Bioinformatics
Abstract

Drosophila melanogaster plays an important role in molecular, genetic, and genomic studies of heredity, development, metabolism, behavior, and human disease. The initial reference genome sequence reported more than a decade ago had a profound impact on progress in Drosophila research, and improving the accuracy and completeness of this sequence continues to be important to further progress. We previously described improvement of the 117-Mb sequence in the euchromatic portion of the genome and 21 Mb in the heterochromatic portion, using a whole-genome shotgun assembly, BAC physical mapping, and clone-based finishing. Here, we report an improved reference sequence of the single-copy and middle-repetitive regions of the genome, produced using cytogenetic mapping to mitotic and polytene chromosomes, clone-based finishing and BAC fingerprint verification, ordering of scaffolds by alignment to cDNA sequences, incorporation of other map and sequence data, and validation by whole-genome optical restriction mapping. These data substantially improve the accuracy and completeness of the reference sequence and the order and orientation of sequence scaffolds into chromosome arm assemblies. Representation of the Y chromosome and other heterochromatic regions is particularly improved. The new 143.9-Mb reference sequence, designated Release 6, effectively exhausts clone-based technologies for mapping and sequencing. Highly repeat-rich regions, including large satellite blocks and functional elements such as the ribosomal RNA genes and the centromeres, are largely inaccessible to current sequencing and assembly methods and remain poorly represented. Further significant improvements will require sequencing technologies that do not depend on molecular cloning and that produce very long reads.

Published
2015

4. Comparative analysis of the transcriptome across distant species.

Author

Gerstein, Mark B, Rozowsky, Joel, Yan, Koon-Kiu, Wang, Daifeng, Cheng, Chao, Brown, James B, Davis, Carrie A, Hillier, LaDeana, Sisu, Cristina, Li, Jingyi Jessica, Pei, Baikang, Harmanci, Arif O, Duff, Michael O, Djebali, Sarah, Alexander, Roger P, Alver, Burak H, Auerbach, Raymond, Bell, Kimberly, Bickel, Peter J, Boeck, Max E, Boley, Nathan P, Booth, Benjamin W, Cherbas, Lucy, Cherbas, Peter, Di, Chao, Dobin, Alex, Drenkow, Jorg, Ewing, Brent, Fang, Gang, Fastuca, Megan, Feingold, Elise A, Frankish, Adam, Gao, Guanjun, Good, Peter J, Guigó, Roderic, Hammonds, Ann, Harrow, Jen, Hoskins, Roger A, Howald, Cédric, Hu, Long, Huang, Haiyan, Hubbard, Tim JP, Huynh, Chau, Jha, Sonali, Kasper, Dionna, Kato, Masaomi, Kaufman, Thomas C, Kitchen, Robert R, Ladewig, Erik, Lagarde, Julien, Lai, Eric, Leng, Jing, Lu, Zhi, MacCoss, Michael, May, Gemma, McWhirter, Rebecca, Merrihew, Gennifer, Miller, David M, Mortazavi, Ali, Murad, Rabi, Oliver, Brian, Olson, Sara, Park, Peter J, Pazin, Michael J, Perrimon, Norbert, Pervouchine, Dmitri, Reinke, Valerie, Reymond, Alexandre, Robinson, Garrett, Samsonova, Anastasia, Saunders, Gary I, Schlesinger, Felix, Sethi, Anurag, Slack, Frank J, Spencer, William C, Stoiber, Marcus H, Strasbourger, Pnina, Tanzer, Andrea, Thompson, Owen A, Wan, Kenneth H, Wang, Guilin, Wang, Huaien, Watkins, Kathie L, Wen, Jiayu, Wen, Kejia, Xue, Chenghai, Yang, Li, Yip, Kevin, Zaleski, Chris, Zhang, Yan, Zheng, Henry, Brenner, Steven E, Graveley, Brenton R, Celniker, Susan E, Gingeras, Thomas R, and Waterston, Robert

Subjects
Chromatin, Animals, Humans, Drosophila melanogaster, Caenorhabditis elegans, Histones, RNA, Untranslated, Cluster Analysis, Gene Expression Profiling, Sequence Analysis, RNA, Gene Expression Regulation, Developmental, Larva, Pupa, Models, Genetic, Promoter Regions, Genetic, Molecular Sequence Annotation, Transcriptome, Genetics, Human Genome, Generic health relevance, General Science & Technology
Abstract

The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly. Uniform processing and comprehensive annotation of these data allow comparison across metazoan phyla, extending beyond earlier within-phylum transcriptome comparisons and revealing ancient, conserved features. Specifically, we discover co-expression modules shared across animals, many of which are enriched in developmental genes. Moreover, we use expression patterns to align the stages in worm and fly development and find a novel pairing between worm embryo and fly pupae, in addition to the embryo-to-embryo and larvae-to-larvae pairings. Furthermore, we find that the extent of non-canonical, non-coding transcription is similar in each organism, per base pair. Finally, we find in all three organisms that the gene-expression levels, both coding and non-coding, can be quantitatively predicted from chromatin features at the promoter using a 'universal model' based on a single set of organism-independent parameters.

Published
2014

5. Comparative validation of the D. melanogaster modENCODE transcriptome annotation

Author

Chen, Zhen-Xia, Sturgill, David, Qu, Jiaxin, Jiang, Huaiyang, Park, Soo, Boley, Nathan, Suzuki, Ana Maria, Fletcher, Anthony R, Plachetzki, David C, FitzGerald, Peter C, Artieri, Carlo G, Atallah, Joel, Barmina, Olga, Brown, James B, Blankenburg, Kerstin P, Clough, Emily, Dasgupta, Abhijit, Gubbala, Sai, Han, Yi, Jayaseelan, Joy C, Kalra, Divya, Kim, Yoo-Ah, Kovar, Christie L, Lee, Sandra L, Li, Mingmei, Malley, James D, Malone, John H, Mathew, Tittu, Mattiuzzo, Nicolas R, Munidasa, Mala, Muzny, Donna M, Ongeri, Fiona, Perales, Lora, Przytycka, Teresa M, Pu, Ling-Ling, Robinson, Garrett, Thornton, Rebecca L, Saada, Nehad, Scherer, Steven E, Smith, Harold E, Vinson, Charles, Warner, Crystal B, Worley, Kim C, Wu, Yuan-Qing, Zou, Xiaoyan, Cherbas, Peter, Kellis, Manolis, Eisen, Michael B, Piano, Fabio, Kionte, Karin, Fitch, David H, Sternberg, Paul W, Cutter, Asher D, Duff, Michael O, Hoskins, Roger A, Graveley, Brenton R, Gibbs, Richard A, Bickel, Peter J, Kopp, Artyom, Carninci, Piero, Celniker, Susan E, Oliver, Brian, and Richards, Stephen

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Biotechnology, Generic health relevance, Animals, Cluster Analysis, Computational Biology, Drosophila melanogaster, Evolution, Molecular, Exons, Female, Gene Expression Profiling, Genome, Insect, Humans, Male, Molecular Sequence Annotation, Nucleotide Motifs, Phylogeny, Position-Specific Scoring Matrices, Promoter Regions, Genetic, RNA Editing, RNA Splice Sites, RNA Splicing, Reproducibility of Results, Transcription Initiation Site, Transcriptome, Medical and Health Sciences, Bioinformatics
Abstract

Accurate gene model annotation of reference genomes is critical for making them useful. The modENCODE project has improved the D. melanogaster genome annotation by using deep and diverse high-throughput data. Since transcriptional activity that has been evolutionarily conserved is likely to have an advantageous function, we have performed large-scale interspecific comparisons to increase confidence in predicted annotations. To support comparative genomics, we filled in divergence gaps in the Drosophila phylogeny by generating draft genomes for eight new species. For comparative transcriptome analysis, we generated mRNA expression profiles on 81 samples from multiple tissues and developmental stages of 15 Drosophila species, and we performed cap analysis of gene expression in D. melanogaster and D. pseudoobscura. We also describe conservation of four distinct core promoter structures composed of combinations of elements at three positions. Overall, each type of genomic feature shows a characteristic divergence rate relative to neutral models, highlighting the value of multispecies alignment in annotating a target genome that should prove useful in the annotation of other high priority genomes, especially human and other mammalian genomes that are rich in noncoding sequences. We report that the vast majority of elements in the annotation are evolutionarily conserved, indicating that the annotation will be an important springboard for functional genetic testing by the Drosophila community.

Published
2014

7. Sequence finishing and mapping of Drosophila melanogaster heterochromatin

Author

Hoskins, Roger A., Carlson, Joseph W., Kennedy, Cameron, Acevedo, David, Evans-Holm, Martha, Frise, Erwin, Wan, Kenneth H., Park, Soo, Mendez-Lago, Maria, Rossi, Fabrizio, Villasante, Alfredo, Dimitri, Patrizio, Karpen, Gary H., and Celniker, Susan E.

Subjects
Basic biological sciences, heterochromatin Drosophila repeated DNA sequence assembly BAC FISH
Abstract

Genome sequences for most metazoans are incomplete due to the presence of repeated DNA in the pericentromeric heterochromatin. The heterochromatic regions of D. melanogaster contain 20 Mb of sequence amenable to mapping, sequence assembly and finishing. Here we describe the generation of 15 Mb of finished or improved heterochromatic sequence using available clone resources and assembly and mapping methods. We also constructed a BAC-based physical map that spans approximately 13 Mb of the pericentromeric heterochromatin, and a cytogenetic map that positions approximately 11 Mb of BAC contigs and sequence scaffolds in specific chromosomal locations. The integrated sequence assembly and maps greatly improve our understanding of the structure and composition of this poorly understood fraction of a metazoan genome and provide a framework for functional analyses.

Published
2008

8. Drosophila by the dozen

Author

Celniker, Susan E. and Hoskins, Roger A.

Subjects
Basic biological sciences, Drosophila genome
Abstract

This year's conference on Drosophila research illustrated well the current focus of Drosophila genomics on the comprehensive identification of functional elements in the genome sequence, including mRNA transcripts arising from multiple alternative start sites and splice sites, a multiplicity of noncoding transcripts and small RNAs, identification of binding sites for transcription factors, sequence conservation in related species and sequence variation within species. Resources and technologies for genetics and functional genomics are steadily being improved, including the building of collections of transposon insertion mutants and hairpin constructs for RNA interference (RNAi). The conference also highlighted progress in the use of genomic information by many laboratories to study diverse aspects of biology and models of human disease. Here we will review a few highlights of especial interest to readers of Genome Biology.

Published
2007

9. High-Throughput Plasmid cDNA Library Screening

Author

Wan, Kenneth H., Yu, Charles, George, Reed A., Carlson, Joseph W., Hoskins, Roger A., Svirskas, Robert, Stapleton, Mark, and Celniker, Susan E.

Subjects
Basic biological sciences, PCR cDNA library screening
Abstract

Libraries of cDNA clones are valuable resources for analysing the expression, structure, and regulation of genes, as well as for studying protein functions and interactions. Full-length cDNA clones provide information about intron and exon structures, splice junctions and 5'- and 3'-untranslated regions (UTRs). Open reading frames (ORFs) derived from cDNA clones can be used to generate constructs allowing expression of native proteins and N- or C-terminally tagged proteins. Thus, obtaining full-length cDNA clones and sequences for most or all genes in an organism is critical for understanding genome functions. Expressed sequence tag (EST) sequencing samples cDNA libraries at random, which is most useful at the beginning of large-scale screening projects. However, as projects progress towards completion, the probability of identifying unique cDNAs via EST sequencing diminishes, resulting in poor recovery of rare transcripts. We describe an adapted, high-throughput protocol intended for recovery of specific, full-length clones from plasmid cDNA libraries in five days.

Published
2006

10. A BAC-Based Physical Map of the Major Autosomes of Drosophila melanogaster

Author

Hoskins, Roger A., Nelson, Catherine R., Berman, Benjamin P., Laverty, Todd R., George, Reed A., Ciesiolka, Lisa, Naeemuddin, Mohammed, Arenson, Andrew D., Durbin, James, David, Robert G., Tabor, Paul E., Bailey, Michael R., DeShazo, Denise R., Catanese, Joseph, Mammoser, Aaron, Osoegawa, Kazutoyo, de Jong, Pieter J., Celniker, Susan E., Gibbs, Richard A., Rubin, Gerald M., and Scherer, Steven E.

Published
2000

11. The Genome Sequence of Drosophila melanogaster

Author

Adams, Mark D., Celniker, Susan E., Holt, Robert A., Evans, Cheryl A., Gocayne, Jeannine D., Amanatides, Peter G., Scherer, Steven E., Li, Peter W., Hoskins, Roger A., Galle, Richard F., George, Reed A., Lewis, Suzanna E., Richards, Stephen, Ashburner, Michael, Henderson, Scott N., Sutton, Granger G., Wortman, Jennifer R., Yandell, Mark D., Zhang, Qing, Chen, Lin X., Brandon, Rhonda C., Rogers, Yu-Hui C., Blazej, Robert G., Champe, Mark, Pfeiffer, Barret D., Wan, Kenneth H., Doyle, Clare, Baxter, Evan G., Helt, Gregg, Nelson, Catherine R., Abril, Josep F., Agbayani, Anna, An, Hui-Jin, Andrews-Pfannkoch, Cynthia, Baldwin, Danita, Ballew, Richard M., Basu, Anand, Baxendale, James, Bayraktaroglu, Leyla, Beasley, Ellen M., Beeson, Karen Y., Benos, P. V., Berman, Benjamin P., Bhandari, Deepali, Bolshakov, Slava, Borkova, Dana, Botchan, Michael R., Bouck, John, Brokstein, Peter, Brottier, Phillipe, Burtis, Kenneth C., Busam, Dana A., Butler, Heather, Cadieu, Edouard, Chandra, Ishwar, Cherry, J. Michael, Cawley, Simon, Dahlke, Carl, Davenport, Lionel B., Davies, Peter, de Pablos, Beatriz, Delcher, Arthur, Deng, Zuoming, Mays, Anne Deslattes, Dew, Ian, Dietz, Suzanne M., Dodson, Kristina, Doup, Lisa E., Downes, Michael, Dugan-Rocha, Shannon, Dunkov, Boris C., Dunn, Patrick, Durbin, Kenneth J., Evangelista, Carlos C., Ferraz, Concepcion, Ferriera, Steven, Fleischmann, Wolfgang, Fosler, Carl, Gabrielian, Andrei E., Garg, Neha S., Gelbart, William M., Glasser, Ken, Glodek, Anna, Gong, Fangcheng, Gorrell, J. Harley, Gu, Zhiping, Guan, Ping, Harris, Michael, Harris, Nomi L., Harvey, Damon, Heiman, Thomas J., Hernandez, Judith R., Houck, Jarrett, Hostin, Damon, Houston, Kathryn A., Howland, Timothy J., Wei, Ming-Hui, Ibegwam, Chinyere, Jalali, Mena, Kalush, Francis, Karpen, Gary H., Ke, Zhaoxi, Kennison, James A., Ketchum, Karen A., Kimmel, Bruce E., Kodira, Chinnappa D., Kraft, Cheryl, Kravitz, Saul, Kulp, David, Lai, Zhongwu, Lasko, Paul, Lei, Yiding, Levitsky, Alexander A., Li, Jiayin, Li, Zhenya, Liang, Yong, Lin, Xiaoying, Liu, Xiangjun, Mattei, Bettina, McIntosh, Tina C., McLeod, Michael P., McPherson, Duncan, Merkulov, Gennady, Milshina, Natalia V., Mobarry, Clark, Morris, Joe, Moshrefi, Ali, Mount, Stephen M., Moy, Mee, Murphy, Brian, Murphy, Lee, Muzny, Donna M., Nelson, David L., Nelson, David R., Nelson, Keith A., Nixon, Katherine, Nusskern, Deborah R., Pacleb, Joanne M., Palazzolo, Michael, Pittman, Gjange S., Pan, Sue, Pollard, John, Puri, Vinita, Reese, Martin G., Reinert, Knut, Remington, Karin, Scheeler, Frederick, Shen, Hua, Shue, Bixiang Christopher, Sidén-Kiamos, Inga, Simpson, Michael, Skupski, Marian P., Smith, Tom, Spier, Eugene, Spradling, Allan C., Stapleton, Mark, Strong, Renee, Sun, Eric, Svirskas, Robert, Tector, Cyndee, Turner, Russell, Venter, Eli, Wang, Aihui H., Wang, Xin, Wang, Zhen-Yuan, Wassarman, David A., Weinstock, George M., Weissenbach, Jean, Williams, Sherita M., Woodage, Trevor, Worley, Kim C., Wu, David, Yang, Song, Yao, Q. Alison, Ye, Jane, Yeh, Ru-Fang, Zaveri, Jayshree S., Zhan, Ming, Zhang, Guangren, Zhao, Qi, Zheng, Liansheng, Zheng, Xiangqun H., Zhong, Fei N., Zhong, Wenyan, Zhou, Xiaojun, Zhu, Shiaoping, Zhu, Xiaohong, Smith, Hamilton O., Gibbs, Richard A., Myers, Eugene W., Rubin, Gerald M., and Venter, J. Craig

Published
2000

12. Comparative Genomics of the Eukaryotes

Author

Rubin, Gerald M., Yandell, Mark D., Wortman, Jennifer R., Nelson, Catherine R., Hariharan, Iswar K., Fortini, Mark E., Li, Peter W., Apweiler, Rolf, Fleischmann, Wolfgang, Cherry, J. Michael, Henikoff, Steven, Skupski, Marian P., Misra, Sima, Ashburner, Michael, Birney, Ewan, Boguski, Mark S., Brody, Thomas, Brokstein, Peter, Celniker, Susan E., Chervitz, Stephen A., Coates, David, Cravchik, Anibal, Gabrielian, Andrei, Galle, Richard F., Gelbart, William M., George, Reed A., Gong, Fangcheng, Guan, Ping, Harris, Nomi L., Hay, Bruce A., Hoskins, Roger A., Li, Jiayin, Li, Zhenya, Hynes, Richard O., Jones, S. J. M., Kuehl, Peter M., Lemaitre, Bruno, Littleton, J. Troy, Morrison, Deborah K., Mungall, Chris, O'Farrell, Patrick H., Pickeral, Oxana K., Shue, Chris, Vosshall, Leslie B., Zhang, Jiong, Zhao, Qi, Zheng, Xiangqun H., Zhong, Fei, Zhong, Wenyan, Gibbs, Richard, Venter, J. Craig, Adams, Mark D., and Lewis, Suzanna

Published
2000

13. Rapid and Efficient cDNA Library Screening by Self-Ligation of Inverse PCR Products (SLIP)

Author

Hoskins, Roger A., Stapleton, Mark, George, Reed A., Yu, Charles, Wan, Kenneth H., Carlson, Joseph W., and Celniker, Susan E.

Subjects
Basic biological sciences, cDNA transcriptome EST
Abstract

The production of comprehensive cDNA clone collections is an important goal of the human and model organism genome projects. cDNA sequences are used to determine the structures of transcripts, including splice junctions, polyadenylation sites, and 5' and 3' untranslated regions (UTRs). cDNA collections are also valuable resources for functional studies of genes and proteins. Expressed Sequence Tag (EST) sequencing is the method of choice for recovering cDNAs representing a majority of the transcripts encoded in a eukaryotic genome. However, EST sequencing samples a library at random, so it realizes diminishing returns as the project progresses. To drive cDNA collections toward completion new methods are needed to recover cDNAs representing specific genes and alternative transcripts, including transcripts with low expression levels. We describe a simple and effective inverse-PCR-based method for screening plasmid libraries to recover intact cDNAs for specific transcripts. We tested the method by screening libraries used in our Drosophila EST projects for 153 transcription factor genes that were not yet represented by full-length cDNAs. We recovered target-specific clones for 104 of the genes: 46 exactly match, 30 improve and 28 partially match current gene annotations. Successful application of the screening method depends on cDNA library complexity and quality of the gene models. The approach should be effective for improving cDNA collections for other model organisms and the human. It also provides a simple and rapid method for isolating cDNAs of interest in any system for which plasmid cDNA libraries and complete or partial gene sequences are available.

Published
2005

14. A BAC-based physical map of the Drosophila buzzatii genome

Author

Gonzalez, Josefa, Nefedov, Michael, Bosdet, Ian, Casals, Ferran, Calvete, Oriol, Delprat, Alejandra, Shin, Heesun, Chiu, Readman, Mathewson, Carrie, Wye, Natasja, Hoskins, Roger A., Schein, Jacqueline E., de Jong, Pieter, and Ruiz, Alfredo

Subjects
Basic biological sciences, BAC Drosophila physical map
Abstract

Large-insert genomic libraries facilitate cloning of large genomic regions, allow the construction of clone-based physical maps and provide useful resources for sequencing entire genomes. Drosophila buzzatii is a representative species of the repleta group in the Drosophila subgenus, which is being widely used as a model in studies of genome evolution, ecological adaptation and speciation. We constructed a Bacterial Artificial Chromosome (BAC) genomic library of D. buzzatii using the shuttle vector pTARBAC2.1. The library comprises 18,353 clones with an average insert size of 152 kb and a ~;18X expected representation of the D. buzzatii euchromatic genome. We screened the entire library with six euchromatic gene probes and estimated the actual genome representation to be ~;23X. In addition, we fingerprinted by restriction digestion and agarose gel electrophoresis a sample of 9,555 clones, and assembled them using FingerPrinted Contigs (FPC) software and manual editing into 345 contigs (mean of 26 clones per contig) and 670 singletons. Finally, we anchored 181 large contigs (containing 7,788 clones) to the D. buzzatii salivary gland polytene chromosomes by in situ hybridization of 427 representative clones. The BAC library and a database with all the information regarding the high coverage BAC-based physical map described in this paper are available to the research community.

Published
2005

15. The BDGP gene disruption project: Single transposon insertions associated with 40% of Drosophila genes

Author

Bellen, Hugo J., Levis, Robert W., Liao, Guochun, He, Yuchun, Carlson, Joseph W., Tsang, Garson, Evans-Holm, Martha, Hiesinger, P. Robin, Schulze, Karen L., Rubin, Gerald M., Hoskins, Roger A., and Spradling, Allan C.

Subjects
Drosophila transposon P-element piggyBac mutagenesis
Abstract

The Berkeley Drosophila Genome Project (BDGP) strives to disrupt each Drosophila gene by the insertion of a single transposable element. As part of this effort, transposons in more than 30,000 fly strains were localized and analyzed relative to predicted Drosophila gene structures. Approximately 6,300 lines that maximize genomic coverage were selected to be sent to the Bloomington Stock Center for public distribution, bringing the size of the BDGP gene disruption collection to 7,140 lines. It now includes individual lines predicted to disrupt 5,362 of the 13,666 currently annotated Drosophila genes (39%). Other lines contain an insertion at least 2 kb from others in the collection and likely mutate additional incompletely annotated or uncharacterized genes and chromosomal regulatory elements. The remaining strains contain insertions likely to disrupt alternative gene promoters or to allow gene mis-expression. The expanded BDGP gene disruption collection provides a public resource that will facilitate the application of Drosophila genetics to diverse biological problems. Finally, the project reveals new insight into how transposons interact with a eukaryotic genome and helps define optimal strategies for using insertional mutagenesis as a genomic tool.

Published
2004

16. Heterochromatic sequences in a Drosophila whole-genome shotgun assembly.

Author

Hoskins, Roger A, Smith, Christopher D, Carlson, Joseph W, Carvalho, A Bernardo, Halpern, Aaron, Kaminker, Joshua S, Kennedy, Cameron, Mungall, Chris J, Sullivan, Beth A, Sutton, Granger G, Yasuhara, Jiro C, Wakimoto, Barbara T, Myers, Eugene W, Celniker, Susan E, Rubin, Gerald M, and Karpen, Gary H

Subjects
Heterochromatin, Animals, Drosophila melanogaster, DNA Transposable Elements, Contig Mapping, Sequence Analysis, DNA, Genome, Algorithms, Software, Databases, Genetic, Sequence Analysis, DNA, Databases, Genetic, Bioinformatics, Environmental Sciences, Biological Sciences, Information and Computing Sciences
Abstract

BACKGROUND:Most eukaryotic genomes include a substantial repeat-rich fraction termed heterochromatin, which is concentrated in centric and telomeric regions. The repetitive nature of heterochromatic sequence makes it difficult to assemble and analyze. To better understand the heterochromatic component of the Drosophila melanogaster genome, we characterized and annotated portions of a whole-genome shotgun sequence assembly. RESULTS:WGS3, an improved whole-genome shotgun assembly, includes 20.7 Mb of draft-quality sequence not represented in the Release 3 sequence spanning the euchromatin. We annotated this sequence using the methods employed in the re-annotation of the Release 3 euchromatic sequence. This analysis predicted 297 protein-coding genes and six non-protein-coding genes, including known heterochromatic genes, and regions of similarity to known transposable elements. Bacterial artificial chromosome (BAC)-based fluorescence in situ hybridization analysis was used to correlate the genomic sequence with the cytogenetic map in order to refine the genomic definition of the centric heterochromatin; on the basis of our cytological definition, the annotated Release 3 euchromatic sequence extends into the centric heterochromatin on each chromosome arm. CONCLUSIONS:Whole-genome shotgun assembly produced a reliable draft-quality sequence of a significant part of the Drosophila heterochromatin. Annotation of this sequence defined the intron-exon structures of 30 known protein-coding genes and 267 protein-coding gene models. The cytogenetic mapping suggests that an additional 150 predicted genes are located in heterochromatin at the base of the Release 3 euchromatic sequence. Our analysis suggests strategies for improving the sequence and annotation of the heterochromatic portions of the Drosophila and other complex genomes.

Published
2002

17. CAGI, the Critical Assessment of Genome Interpretation, establishes progress and prospects for computational genetic variant interpretation methods.

Author

The Critical Assessment of Genome Interpretation Consortium, Jain, Shantanu, Bakolitsa, Constantina, Brenner, Steven E., Radivojac, Predrag, Moult, John, Repo, Susanna, Hoskins, Roger A., Andreoletti, Gaia, Barsky, Daniel, Chellapan, Ajithavalli, Chu, Hoyin, Dabbiru, Navya, Kollipara, Naveen K., Ly, Melissa, Neumann, Andrew J., Pal, Lipika R., Odell, Eric, Pandey, Gaurav, and Peters-Petrulewicz, Robin C.

Published
2024
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18. Working toward precision medicine: Predicting phenotypes from exomes in the Critical Assessment of Genome Interpretation (CAGI) challenges

Author

Daneshjou, Roxana, Wang, Yanran, Bromberg, Yana, Bovo, Samuele, Martelli, Pier L, Babbi, Giulia, Lena, Pietro Di, Casadio, Rita, Edwards, Matthew, Gifford, David, Jones, David T, Sundaram, Laksshman, Bhat, Rajendra Rana, Li, Xiaolin, Pal, Lipika R., Kundu, Kunal, Yin, Yizhou, Moult, John, Jiang, Yuxiang, Pejaver, Vikas, Pagel, Kymberleigh A., Li, Biao, Mooney, Sean D., Radivojac, Predrag, Shah, Sohela, Carraro, Marco, Gasparini, Alessandra, Leonardi, Emanuela, Giollo, Manuel, Ferrari, Carlo, Tosatto, Silvio C E, Bachar, Eran, Azaria, Johnathan R., Ofran, Yanay, Unger, Ron, Niroula, Abhishek, Vihinen, Mauno, Chang, Billy, Wang, Maggie H, Franke, Andre, Petersen, Britt-Sabina, Pirooznia, Mehdi, Zandi, Peter, McCombie, Richard, Potash, James B., Altman, Russ B., Klein, Teri E., Hoskins, Roger A., Repo, Susanna, Brenner, Steven E., and Morgan, Alexander A.

Published
2017
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21. Identification of Functional Elements and Regulatory Circuits by Drosophila modENCODE

Author

The modeENCODE Consortium, Roy, Sushmita, Ernst, Jason, Kharchenko, Peter V., Kheradpour, Pouya, Negre, Nicolas, Eaton, Matthew L., Landolin, Jane M., Bristow, Christopher A., Ma, Lijia, Lin, Michael F., Washietl, Stefan, Arshinoff, Bradley I., Ay, Ferhat, Meyer, Patrick E., Robine, Nicolas, Washington, Nicole L., Di Stefano, Luisa, Berezikov, Eugene, Brown, Christopher D., Candeias, Rogerio, Carlson, Joseph W., Carr, Adrian, Jungreis, Irwin, Marbach, Daniel, Sealfon, Rachel, Tolstorukov, Michael Y., Will, Sebastian, Alekseyenko, Artyom A., Artieri, Carlo, Booth, Benjamin W., Brooks, Angela N., Dai, Qi, Davis, Carrie A., Duff, Michael O., Feng, Xin, Gorchakov, Andrey A., Gu, Tingting, Henikoff, Jorja G., Kapranov, Philipp, Li, Renhua, MacAlpine, Heather K., Malone, John, Minoda, Aki, Nordman, Jared, Okamura, Katsutomo, Perry, Marc, Powell, Sara K., Riddle, Nicole C., Sakai, Akiko, Samsonova, Anastasia, Sandler, Jeremy E., Schwartz, Yuri B., Sher, Noa, Spokony, Rebecca, Sturgill, David, van Baren, Marijke, Wan, Kenneth H., Yang, Li, Yu, Charles, Feingold, Elise, Good, Peter, Guyer, Mark, Lowdon, Rebecca, Ahmad, Kami, Andrews, Justen, Berger, Bonnie, Brenner, Steven E., Brent, Michael R., Cherbas, Lucy, Elgin, Sarah C. R., Gingeras, Thomas R., Grossman, Robert, Hoskins, Roger A., Kaufman, Thomas C., Kent, William, Kuroda, Mitzi I., Orr-Weaver, Terry, Perrimon, Norbert, Pirrotta, Vincenzo, Posakony, James W., Ren, Bing, Russell, Steven, Cherbas, Peter, Graveley, Brenton R., Lewis, Suzanna, Micklem, Gos, Oliver, Brian, Park, Peter J., Celniker, Susan E., Henikoff, Steven, Karpen, Gary H., Lai, Eric C., MacAlpine, David M., Stein, Lincoln D., White, Kevin P., and Kellis, Manolis

Published
2010

24. A molecularly defined duplication set for the X chromosome of Drosophila melanogaster

Author

Venken, Koen J.T., Popodi, Ellen, Holtzman, Stacy L., Schulze, Karen L., Park, Soo, Carlson,Joseph W., Hoskins, Roger A., Bellen, Hugo J., and Kaufman, Thomas C.

Subjects
Chromosome replication -- Research, Gene amplification -- Research, Gene mutations -- Research, X chromosome -- Research, Biological sciences
Published
2010

25. Diversity and dynamics of the Drosophila transcriptome

Author

Brown, James B., Boley, Nathan, Eisman, Robert, May, Gemma E., Stoiber, Marcus H., Duff, Michael O., Booth, Ben W., Wen, Jiayu, Park, Soo, Suzuki, Ana Maria, Wan, Kenneth H., Yu, Charles, Zhang, Dayu, Carlson, Joseph W., Cherbas, Lucy, Eads, Brian D., Miller, David, Mockaitis, Keithanne, Roberts, Johnny, Davis, Carrie A., Frise, Erwin, Hammonds, Ann S., Olson, Sara, Shenker, Sol, Sturgill, David, Samsonova, Anastasia A., Weiszmann, Richard, Robinson, Garret, Hernandez, Juan, Andrews, Justen, Bickel, Peter J., Carninci, Piero, Cherbas, Peter, Gingeras, Thomas R., Hoskins, Roger A., Kaufman, Thomas C., Lai, Eric C., Oliver, Brian, Perrimon, Norbert, Graveley, Brenton R., and Celniker, Susan E.

Published
2014
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26. Working toward precision medicine: Predicting phenotypes from exomes in the Critical Assessment of Genome Interpretation (CAGI) challenges

Author

Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Daneshjou, Roxana, Wang, Yanran, Bromberg, Yana, Bovo, Samuele, Martelli, Pier L, Babbi, Giulia, Di Lena, Pietro, Casadio, Rita, Edwards, Matthew D, Gifford, David K, Jones, David T, Sundaram, Laksshman, Bhat, Rajendra, Li, Xiaolin, Pal, Lipika R., Kundu, Kunal, Yin, Yizhou, Moult, John, Jiang, Yuxiang, Pejaver, Vikas, Pagel, Kymberleigh A., Li, Biao, Mooney, Sean D., Radivojac, Predrag, Shah, Sohela, Carraro, Marco, Gasparini, Alessandra, Leonardi, Emanuela, Giollo, Manuel, Ferrari, Carlo, Tosatto, Silvio C E, Bachar, Eran, Azaria, Johnathan R., Ofran, Yanay, Unger, Ron, Niroula, Abhishek, Vihinen, Mauno, Chang, Billy, Wang, Maggie H, Franke, Andre, Petersen, Britt-Sabina, Pirooznia, Mehdi, Zandi, Peter, McCombie, Richard, Potash, James B, Altman, Russ, Klein, Teri E., Hoskins, Roger, Repo, Susanna, Brenner, Steve E, Morgan, Alexander A, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Daneshjou, Roxana, Wang, Yanran, Bromberg, Yana, Bovo, Samuele, Martelli, Pier L, Babbi, Giulia, Di Lena, Pietro, Casadio, Rita, Edwards, Matthew D, Gifford, David K, Jones, David T, Sundaram, Laksshman, Bhat, Rajendra, Li, Xiaolin, Pal, Lipika R., Kundu, Kunal, Yin, Yizhou, Moult, John, Jiang, Yuxiang, Pejaver, Vikas, Pagel, Kymberleigh A., Li, Biao, Mooney, Sean D., Radivojac, Predrag, Shah, Sohela, Carraro, Marco, Gasparini, Alessandra, Leonardi, Emanuela, Giollo, Manuel, Ferrari, Carlo, Tosatto, Silvio C E, Bachar, Eran, Azaria, Johnathan R., Ofran, Yanay, Unger, Ron, Niroula, Abhishek, Vihinen, Mauno, Chang, Billy, Wang, Maggie H, Franke, Andre, Petersen, Britt-Sabina, Pirooznia, Mehdi, Zandi, Peter, McCombie, Richard, Potash, James B, Altman, Russ, Klein, Teri E., Hoskins, Roger, Repo, Susanna, Brenner, Steve E, and Morgan, Alexander A

Abstract

Precision medicine aims to predict a patient's disease risk and best therapeutic options by using that individual's genetic sequencing data. The Critical Assessment of Genome Interpretation (CAGI) is a community experiment consisting of genotype–phenotype prediction challenges; participants build models, undergo assessment, and share key findings. For CAGI 4, three challenges involved using exome-sequencing data: Crohn's disease, bipolar disorder, and warfarin dosing. Previous CAGI challenges included prior versions of the Crohn's disease challenge. Here, we discuss the range of techniques used for phenotype prediction as well as the methods used for assessing predictive models. Additionally, we outline some of the difficulties associated with making predictions and evaluating them. The lessons learned from the exome challenges can be applied to both research and clinical efforts to improve phenotype prediction from genotype. In addition, these challenges serve as a vehicle for sharing clinical and research exome data in a secure manner with scientists who have a broad range of expertise, contributing to a collaborative effort to advance our understanding of genotype–phenotype relationships.

Published
2021

27. Evolution of genes and genomes on the Drosophila phylogeny

Author

Clark, Andrew G., Eisen, Michael B., Smith, Douglas R., Bergman, Casey M., Oliver, Brian, Markow, Therese A., Kaufman, Thomas C., Kellis, Manolis, Gelbart, William, Iyer, Venky N., Pollard, Daniel A., Sackton, Timothy B., Larracuente, Amanda M., Singh, Nadia D., Abad, Jose P., Abt, Dawn N., Adryan, Boris, Aguade, Montserrat, Akashi, Hiroshi, Anderson, Wyatt W., Aquadro, Charles F., Ardell, David H., Arguello, Roman, Artieri, Carlo G., Barbash, Daniel A., Barker, Daniel, Barsanti, Paolo, Batterham, Phil, Batzoglou, Serafim, Begun, Dave, Bhutkar, Arjun, Blanco, Enrico, Bosak, Stephanie A., Bradley, Robert K., Brand, Adrianne D., Brent, Michael R., Brooks, Angela N., Brown, Randall H., Butlin, Roger K., Caggese, Corrado, Calvi, Brian R., Bernardo de Carvalho, A., Caspi, Anat, Castrezana, Sergio, Celniker, Susan E., Chang, Jean L., Chapple, Charles, Chatterji, Sourav, Chinwalla, Asif, Civetta, Alberto, Clifton, Sandra W., Comeron, Josep M., Costello, James C., Coyne, Jerry A., Daub, Jennifer, David, Robert G., Delcher, Arthur L., Delehaunty, Kim, Do, Chuong B., Ebling, Heather, Edwards, Kevin, Eickbush, Thomas, Evans, Jay D., Filipski, Alan, Findeiß, Sven, Freyhult, Eva, Fulton, Lucinda, Fulton, Robert, Garcia, Ana C. L., Gardiner, Anastasia, Garfield, David A., Garvin, Barry E., Gibson, Greg, Gilbert, Don, Gnerre, Sante, Godfrey, Jennifer, Good, Robert, Gotea, Valer, Gravely, Brenton, Greenberg, Anthony J., Griffiths-Jones, Sam, Gross, Samuel, Guigo, Roderic, Gustafson, Erik A., Haerty, Wilfried, Hahn, Matthew W., Halligan, Daniel L., Halpern, Aaron L., Halter, Gillian M., Han, Mira V., Heger, Andreas, Hillier, LaDeana, Hinrichs, Angie S., Holmes, Ian, Hoskins, Roger A., Hubisz, Melissa J., Hultmark, Dan, Huntley, Melanie A., Jaffe, David B., Jagadeeshan, Santosh, Jeck, William R., Johnson, Justin, Jones, Corbin D., Jordan, William C., Karpen, Gary H., Kataoka, Eiko, Keightley, Peter D., Kheradpour, Pouya, Kirkness, Ewen F., Koerich, Leonardo B., Kristiansen, Karsten, Kudrna, Dave, Kulathinal, Rob J., Kumar, Sudhir, Kwok, Roberta, Lander, Eric, Langley, Charles H., Lapoint, Richard, Lazzaro, Brian P., Lee, So-Jeong, Levesque, Lisa, Li, Ruiqiang, Lin, Chiao-Feng, Lin, Michael F., Lindblad-Toh, Kerstin, Llopart, Ana, Long, Manyuan, Low, Lloyd, Lozovsky, Elena, Lu, Jian, Luo, Meizhong, Machado, Carlos A., Makalowski, Wojciech, Marzo, Mar, Matsuda, Muneo, Matzkin, Luciano, McAllister, Bryant, McBride, Carolyn S., McKernan, Brendan, McKernan, Kevin, Mendez-Lago, Maria, Minx, Patrick, Mollenhauer, Michael U., Montooth, Kristi, Mount, Stephen M., Mu, Xu, Myers, Eugene, Negre, Barbara, Newfeld, Stuart, Nielsen, Rasmus, Noor, Mohamed A. F., O'Grady, Patrick, Pachter, Lior, Papaceit, Montserrat, Parisi, Matthew J., Parisi, Michael, Parts, Leopold, Pedersen, Jakob S., Pesole, Graziano, Phillippy, Adam M., Ponting, Chris P., Pop, Mihai, Porcelli, Damiano, Powell, Jeffrey R., Prohaska, Sonja, Pruitt, Kim, Puig, Marta, Quesneville, Hadi, Ravi Ram, Kristipati, Rand, David, Rasmussen, Matthew D., Reed, Laura K., Reenan, Robert, Reily, Amy, Remington, Karin A., Rieger, Tania T., Ritchie, Michael G., Robin, Charles, Rogers, Yu-Hui, Rohde, Claudia, Rozas, Julio, Rubenfield, Marc J., Ruiz, Alfredo, Russo, Susan, Salzberg, Steven L., Sanchez-Gracia, Alejandro, Saranga, David J., Sato, Hajime, Schaeffer, Stephen W., Schatz, Michael C., Schlenke, Todd, Schwartz, Russell, Segarra, Carmen, Singh, Rama S., Sirot, Laura, Sirota, Marina, Sisneros, Nicholas B., Smith, Chris D., Smith, Temple F., Spieth, John, Stage, Deborah E., Stark, Alexander, Stephan, Wolfgang, Strausberg, Robert L., Strempel, Sebastian, Sturgill, David, Sutton, Granger, Sutton, Granger G., Tao, Wei, Teichmann, Sarah, Tobari, Yoshiko N., Tomimura, Yoshihiko, Tsolas, Jason M., Valente, Vera L. S., Venter, Eli, Craig Venter, J., Vicario, Saverio, Vieira, Filipe G., Vilella, Albert J., Villasante, Alfredo, Walenz, Brian, Wang, Jun, Wasserman, Marvin, Watts, Thomas, Wilson, Derek, Wilson, Richard K., Wing, Rod A., Wolfner, Mariana F., Wong, Alex, Ka-Shu Wong, Gane, Wu, Chung-I, Wu, Gabriel, Yamamoto, Daisuke, Yang, Hsiao-Pei, Yang, Shiaw-Pyng, Yorke, James A., Yoshida, Kiyohito, Zdobnov, Evgeny, Zhang, Peili, Zhang, Yu, Zimin, Aleksey V., Baldwin, Jennifer, Abdouelleil, Amr, Abdulkadir, Jamal, Abebe, Adal, Abera, Brikti, Abreu, Justin, Christophe Acer, St, Aftuck, Lynne, Alexander, Allen, An, Peter, Anderson, Erica, Anderson, Scott, Arachi, Harindra, Azer, Marc, Bachantsang, Pasang, Barry, Andrew, Bayul, Tashi, Berlin, Aaron, Bessette, Daniel, Bloom, Toby, Blye, Jason, Boguslavskiy, Leonid, Bonnet, Claude, Boukhgalter, Boris, Bourzgui, Imane, Brown, Adam, Cahill, Patrick, Channer, Sheridon, Cheshatsang, Yama, Chuda, Lisa, Citroen, Mieke, Collymore, Alville, Cooke, Patrick, Costello, Maura, D'Aco, Katie, Daza, Riza, De Haan, Georgius, DeGray, Stuart, DeMaso, Christina, Dhargay, Norbu, Dooley, Kimberly, Dooley, Erin, Doricent, Missole, Dorje, Passang, Dorjee, Kunsang, Dupes, Alan, Elong, Richard, Falk, Jill, Farina, Abderrahim, Faro, Susan, Ferguson, Diallo, Fisher, Sheila, Foley, Chelsea D., Franke, Alicia, Friedrich, Dennis, Gadbois, Loryn, Gearin, Gary, Gearin, Christina R., Giannoukos, Georgia, Goode, Tina, Graham, Joseph, Grandbois, Edward, Grewal, Sharleen, Gyaltsen, Kunsang, Hafez, Nabil, Hagos, Birhane, Hall, Jennifer, Henson, Charlotte, Hollinger, Andrew, Honan, Tracey, Huard, Monika D., Hughes, Leanne, Hurhula, Brian, Erii Husby, M, Kamat, Asha, Kanga, Ben, Kashin, Seva, Khazanovich, Dmitry, Kisner, Peter, Lance, Krista, Lara, Marcia, Lee, William, Lennon, Niall, Letendre, Frances, LeVine, Rosie, Lipovsky, Alex, Liu, Xiaohong, Liu, Jinlei, Liu, Shangtao, Lokyitsang, Tashi, Lokyitsang, Yeshi, Lubonja, Rakela, Lui, Annie, MacDonald, Pen, Magnisalis, Vasilia, Maru, Kebede, Matthews, Charles, McCusker, William, McDonough, Susan, Mehta, Teena, Meldrim, James, Meneus, Louis, Mihai, Oana, Mihalev, Atanas, Mihova, Tanya, Mittelman, Rachel, Mlenga, Valentine, Montmayeur, Anna, Mulrain, Leonidas, Navidi, Adam, Naylor, Jerome, Negash, Tamrat, Nguyen, Thu, Nguyen, Nga, Nicol, Robert, Norbu, Choe, Norbu, Nyima, Novod, Nathaniel, O'Neill, Barry, Osman, Sahal, Markiewicz, Eva, Oyono, Otero L., Patti, Christopher, Phunkhang, Pema, Pierre, Fritz, Priest, Margaret, Raghuraman, Sujaa, Rege, Filip, Reyes, Rebecca, Rise, Cecil, Rogov, Peter, Ross, Keenan, Ryan, Elizabeth, Settipalli, Sampath, Shea, Terry, Sherpa, Ngawang, Shi, Lu, Shih, Diana, Sparrow, Todd, Spaulding, Jessica, Stalker, John, Stange-Thomann, Nicole, Stavropoulos, Sharon, Stone, Catherine, Strader, Christopher, Tesfaye, Senait, Thomson, Talene, Thoulutsang, Yama, Thoulutsang, Dawa, Topham, Kerri, Topping, Ira, Tsamla, Tsamla, Vassiliev, Helen, Vo, Andy, Wangchuk, Tsering, Wangdi, Tsering, Weiand, Michael, Wilkinson, Jane, Wilson, Adam, Yadav, Shailendra, Young, Geneva, Yu, Qing, Zembek, Lisa, Zhong, Danni, Zimmer, Andrew, Zwirko, Zac, Alvarez, Pablo, Brockman, Will, Butler, Jonathan, Chin, CheeWhye, Grabherr, Manfred, Kleber, Michael, Mauceli, Evan, and MacCallum, Iain

Abstract

Author(s): Drosophila 12 Genomes Consortium; Project Leaders; Andrew G. Clark (corresponding author) [1]; Michael B. Eisen (corresponding author) [2, 3]; Douglas R. Smith (corresponding author) [4]; Casey M. Bergman (corresponding [...]

Published
2007
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28. Thirty-one flavors of Drosophila Rab proteins

Author

Zhang, Jun, Schulze, Karen L., Hiesinger, P. Robin, Suyama, Kaye, Wang, Stream, Fish, Matthew, Acar, Melih, Hoskins, Roger A., Bellen, Hugo J., and Scott, Matthew P.

Subjects
Drosophila -- Genetic aspects, Drosophila -- Physiological aspects, Drosophila -- Chemical properties, G proteins -- Physiological aspects, G proteins -- Genetic aspects, Gene expression -- Evaluation, Biological sciences
Abstract

Rab proteins are small GTPases that play important roles in transport of vesicle cargo and recruitment, association of motor and other proteins with vesicles, and docking and fusion of vesicles at defined locations. In vertebrates, > 75 Rab genes have been identified, some of which have been intensively studied for their roles in endosome and synaptic vesicle trafficking. Recent studies of the functions of certain Rab proteins have revealed specific roles in mediating developmental signal transduction. We have begun a systematic genetic study of the 33 Rab genes in Drosophila. Most of the fly proteins are clearly related to specific vertebrate proteins. We report here the creation of a set of transgenic fly lines that allow spatially and temporally regulated expression of Drosophila Rab proteins. We generated fluorescent proteintagged wild-type, dominant-negative, and constitutively active forms of 31 Drosophila Rab proteins. We describe Drosophila Rab expression patterns during embryogenesis, the subcellular localization of some Rab proteins, and comparisons of the localization of wild-type, dominant-negative, and constitutively active forms of selected Rab proteins. The high evolutionary conservation and low redundancy of Drosophila Rab proteins make these transgenic lines a useful tool kit for investigating Rab functions in vivo.

Published
2007

29. The Carnegie protein trap library: a versatile tool for Drosophila developmental studies

Author

Buszczak, Michael, Paterno, Shelley, Lighthouse, Daniel, Bachman, Julia, Planck, Jamie, Owen, Stephenie, Skora, Andrew D., Nystul, Todd G., Ohlstein, Benjamin, Allen, Anna, Wilhelm, James E., Murphy, Terence D., Levis, Robert W., Matunis, Erika, Srivali, Nahathai, Hoskins, Roger A., and Spradling, Allan C.

Subjects
Gene expression -- Research, Drosophila -- Genetic aspects, Drosophila -- Research, Metazoa -- Physiological aspects, Metazoa -- Genetic aspects, Metazoa -- Research, Mutagenesis -- Research, Biological sciences
Abstract

Metazoan physiology depends on intricate patterns of gene expression that remain poorly known. Using transposon mutagenesis in Drosophila, we constructed a library of 7404 protein trap and enhancer trap lines, the Carnegie collection, to facilitate gene expression mapping at single-cell resolution. By sequencing the genomic insertion sites, determining splicing patterns downstream of the enhanced green fluorescent protein (EGFP) exon, and analyzing expression patterns in the ovary and salivary gland, we found that 600-900 different genes are trapped in our collection. A core set of 244 lines trapped different identifiable protein isoforms, while insertions likely to act as GFP-enhancer traps were found in 256 additional genes. At least 8 novel genes were also identified. Our results demonstrate that the Carnegie collection will be useful as a discovery tool in diverse areas of cell and developmental biology and suggest new strategies for greatly increasing the coverage of the Drosophila proteome with protein trap insertions.

Published
2007

30. Exploring strategies for protein trapping in Drosophila

Author

Quiniones-Coello, Ana T., Petrella, Lisa N., Ayers, Kathleen, Melillo, Anthony, Mazzalupo, Stacy, Hudson, Andrew M., Wang, Shu, Castiblanco, Claudia, Buszczak, Michael, Hoskins, Roger A., and Cooley, Lynn

Subjects
Drosophila -- Genetic aspects, Drosophila -- Research, Recombinant proteins -- Research, Gene expression -- Research, Biological sciences
Abstract

The use of fluorescent protein tags has had a huge impact on cell biological studies in virtually every experimental system. Incorporation of coding sequence for fluorescent proteins such as green fluorescent protein (GFP) into genes at their endogenous chromosomal position is especially useful for generating GFP-fusion proteins that provide accurate cellular and subcellular expression data. We tested modifications of a transposon-based protein trap screening procedure in Drosophila to optimize the rate of recovering useful protein traps and their analysis. Transposons carrying the GFP-coding sequence flanked by splice acceptor and donor sequences were mobilized, and new insertions that resulted in production of GFP were captured using an automated embryo sorter. Individual stocks were established, GFP expression was analyzed during oogenesis, and insertion sites were determined by sequencing genomic DNA flanking the insertions, The resulting collection includes lines with protein traps in which GFP was spliced into mRNAs and embedded within endogenous proteins or enhancer traps in which GFP expression depended on splicing into transposon-derived RNA, We report a total of 335 genes associated with protein or enhancer traps and a web-accessible database for viewing molecular information and expression data for these genes.

Published
2007

33. The developmental transcriptome of Drosophila melanogaster

Author

Graveley, Brenton R., Brooks, Angela N., Carlson, Joseph W., Duff, Michael O., Landolin, Jane M., Yang, Li, Artieri, Carlo G., van Baren, Marijke J., Boley, Nathan, Booth, Benjamin W., Brown, James B., Cherbas, Lucy, Davis, Carrie A., Dobin, Alex, Li, Renhua, Lin, Wei, Malone, John H., Mattiuzzo, Nicolas R., Miller, David, Sturgill, David, Tuch, Brian B., Zaleski, Chris, Zhang, Dayu, Blanchette, Marco, Dudoit, Sandrine, Eads, Brian, Green, Richard E., Hammonds, Ann, Jiang, Lichun, Kapranov, Phil, Langton, Laura, Perrimon, Norbert, Sandler, Jeremy E., Wan, Kenneth H., Willingham, Aarron, Zhang, Yu, Zou, Yi, Andrews, Justen, Bickel, Peter J., Brenner, Steven E., Brent, Michael R., Cherbas, Peter, Gingeras, Thomas R., Hoskins, Roger A., Kaufman, Thomas C., Oliver, Brian, and Celniker, Susan E.

Published
2011
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34. Identification of Functional Elements and Regulatory Circuits by Drosophila modENCODE

Author

Roy, Sushmita, Ernst, Jason, Kharchenko, Peter V., Kheradpour, Pouya, Negre, Nicolas, Eaton, Matthew L., Landolin, Jane M., Bristow, Christopher A., Ma, Lijia, Lin, Michael F., Washietl, Stefan, Arshinoff, Bradley I., Ay, Ferhat, Meyer, Patrick E., Robine, Nicolas, Washington, Nicole L., Stefano, Luisa Di, Berezikov, Eugene, Brown, Christopher D., Candeias, Rogerio, Carlson, Joseph W., Carr, Adrian, Jungreis, Irwin, Marbach, Daniel, Sealfon, Rachel, Tolstorukov, Michael Y., Will, Sebastian, Alekseyenko, Artyom A., Artieri, Carlo, Booth, Benjamin W., Brooks, Angela N., Dai, Qi, Davis, Carrie A., Duff, Michael O., Feng, Xin, Gorchakov, Andrey A., Gu, Tingting, Henikoff, Jorja G., Kapranov, Philipp, Li, Renhua, MacAlpine, Heather K., Malone, John, Minoda, Aki, Nordman, Jared, Okamura, Katsutomo, Perry, Marc, Powell, Sara K., Riddle, Nicole C., Sakai, Akiko, Samsonova, Anastasia, Sandler, Jeremy E., Schwartz, Yuri B., Sher, Noa, Spokony, Rebecca, Sturgill, David, van Baren, Marijke, Wan, Kenneth H., Yang, Li, Yu, Charles, Feingold, Elise, Good, Peter, Guyer, Mark, Lowdon, Rebecca, Ahmad, Kami, Andrews, Justen, Berger, Bonnie, Brenner, Steven E., Brent, Michael R., Cherbas, Lucy, Elgin, Sarah C. R., Gingeras, Thomas R., Grossman, Robert, Hoskins, Roger A., Kaufman, Thomas C., Kent, William, Kuroda, Mitzi I., Orr-Weaver, Terry, Perrimon, Norbert, Pirrotta, Vincenzo, Posakony, James W., Ren, Bing, Russell, Steven, Cherbas, Peter, Graveley, Brenton R., Lewis, Suzanna, Micklem, Gos, Oliver, Brian, Park, Peter J., Celniker, Susan E., Henikoff, Steven, Karpen, Gary H., Lai, Eric C., MacAlpine, David M., Stein, Lincoln D., White, Kevin P., and Kellis, Manolis

Published
2010
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37. Control of type-D GABAergic neuron differentiation by C. elegans UNC-30 homeodomain protein

Author

Jin, Yishi, Hoskins, Roger, and Horvitz, H. Robert

Subjects
Caenorhabditis elegans -- Research, Gene expression -- Analysis, Neurons -- Research, GABA -- Analysis, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The Caenorhabditis elegans gene unc-30, which codes for a homeodomain protein in the inhibitory GABAergic type D motor neurons, regulates transcription in these neurons, mediating their terminal differentiation. unc-30 activates GABA expression in cells that are non-GABAergic. This gene is expressed at high levels in young larvae having a developed motor circuitry, and at low levels in older animals.

Published
1994

38. Quantitative analysis of bristle number in Drosophila mutants identifies genes involved in neural development

Author

Norga, Koenraad K, Gurganus, Marjorie C, Dilda, Christy L, Yamamoto, Akihiko, Lyman, Richard F, Patel, Prajal H, Rubin, Gerald M, Hoskins, Roger A, Mackay, Trudy F, and Bellen, Hugo J

Subjects
Life Sciences (General)
Abstract

BACKGROUND: The identification of the function of all genes that contribute to specific biological processes and complex traits is one of the major challenges in the postgenomic era. One approach is to employ forward genetic screens in genetically tractable model organisms. In Drosophila melanogaster, P element-mediated insertional mutagenesis is a versatile tool for the dissection of molecular pathways, and there is an ongoing effort to tag every gene with a P element insertion. However, the vast majority of P element insertion lines are viable and fertile as homozygotes and do not exhibit obvious phenotypic defects, perhaps because of the tendency for P elements to insert 5' of transcription units. Quantitative genetic analysis of subtle effects of P element mutations that have been induced in an isogenic background may be a highly efficient method for functional genome annotation. RESULTS: Here, we have tested the efficacy of this strategy by assessing the extent to which screening for quantitative effects of P elements on sensory bristle number can identify genes affecting neural development. We find that such quantitative screens uncover an unusually large number of genes that are known to function in neural development, as well as genes with yet uncharacterized effects on neural development, and novel loci. CONCLUSIONS: Our findings establish the use of quantitative trait analysis for functional genome annotation through forward genetics. Similar analyses of quantitative effects of P element insertions will facilitate our understanding of the genes affecting many other complex traits in Drosophila.

Published
2003
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39. VIPdb, a genetic Variant Impact Predictor Database

Author

Hu, Zhiqiang, primary, Yu, Changhua, additional, Furutsuki, Mabel, additional, Andreoletti, Gaia, additional, Ly, Melissa, additional, Hoskins, Roger, additional, Adhikari, Aashish N., additional, and Brenner, Steven E., additional

Published
2019
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40. Finishing a whole-genome shotgun: Release 3 of the Drosophila melanogastereuchromatic genome sequence

Author

Celniker, Susan E, Wheeler, David A, Kronmiller, Brent, Carlson, Joseph W, Halpern, Aaron, Patel, Sandeep, Adams, Mark, Champe, Mark, Dugan, Shannon P, Frise, Erwin, Hodgson, Ann, George, Reed A, Hoskins, Roger A, Laverty, Todd, Muzny, Donna M, Nelson, Catherine R, Pacleb, Joanne M, Park, Soo, Pfeiffer, Barret D, Richards, Stephen, Sodergren, Erica J, Svirskas, Robert, Tabor, Paul E, Wan, Kenneth, Stapleton, Mark, Sutton, Granger G, Venter, Craig, Weinstock, George, Scherer, Steven E, Myers, Eugene W, Gibbs, Richard A, and Rubin, Gerald M

Published
2002
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43. A BAC-Based Physical Hap of the Major Autosomes of Drosophila melanogaster

Author

Hoskins, Roger A., Nelson, Catherine R., Berman, Benjamin P., Laverty, Todd R., George, Reed A., Ciesiolka, Lisa, Naeemuddin, Mohammed, Arenson, Andrew D., Durbin, James, David, Robert G., Tabor, Paul E., Bailey, Michael R., DeShazo, Denise R., Catanese, Joseph, Mammoser, Aaron, Osoegawa, Kazutoyo, de Jong, Pieter J., Celniker, Susan E., Gibbs, Richard A., Rubin, Gerald M., and Scherer, Steven E.

Subjects
Research, Genetic aspects, Drosophila -- Genetic aspects -- Research, Chromosome mapping -- Research -- Genetic aspects
Abstract

The fruit fly Drosophila melanogaster is a principal model organism in metazoan genetics and molecular biology. Here, we describe a BAC-based physical map of chromosomes 2 and 3 constructed as [...], We constructed a bacterial artificial chromosome (BAC)-based physical map of chromosomes 2 and 3 of Drosophila melanogaster, which constitute 81% of the genome. Sequence tagged site (STS) content, restriction fingerprinting, and polytene chromosome in situ hybridization approaches were integrated to produce a map spanning the euchromatin. Three of five remaining gaps are in repeat-rich regions near the centromeres. A tiling path of clones spanning this map and STS maps of chromosomes X and 4 was sequenced to low coverage; the maps and tiring path sequence were used to support and verify the whole- genome sequence assembly, and tiring path BACs were used as templates in sequence finishing.

Published
2000

44. The Release 6 reference sequence of the Drosophila melanogaster genome

Author

Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil), Fondazione Cenci Bolognetti, University of California, Ministry of Education and Science of the Russian Federation, Ministerio de Economía y Competitividad (España), Hoskins, Roger A., Menéndez-Lago, María, Pablos, Beatriz de, Celniker, Susan E., Villasante, Alfredo, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Conselho Nacional de Desenvolvimento Científico e Tecnológico (Brasil), Fondazione Cenci Bolognetti, University of California, Ministry of Education and Science of the Russian Federation, Ministerio de Economía y Competitividad (España), Hoskins, Roger A., Menéndez-Lago, María, Pablos, Beatriz de, Celniker, Susan E., and Villasante, Alfredo

Abstract

Drosophila melanogaster plays an important role in molecular, genetic, and genomic studies of heredity, development, metabolism, behavior, and human disease. The initial reference genome sequence reported more than a decade ago had a profound impact on progress in Drosophila research, and improving the accuracy and completeness of this sequence continues to be important to further progress. We previously described improvement of the 117-Mb sequence in the euchromatic portion of the genome and 21 Mb in the heterochromatic portion, using a whole-genome shotgun assembly, BAC physical mapping, and clone-based finishing. Here, we report an improved reference sequence of the single-copy and middle-repetitive regions of the genome, produced using cytogenetic mapping to mitotic and polytene chromosomes, clone-based finishing and BAC fingerprint verification, ordering of scaffolds by alignment to cDNA sequences, incorporation of other map and sequence data, and validation by whole-genome optical restriction mapping. These data substantially improve the accuracy and completeness of the reference sequence and the order and orientation of sequence scaffolds into chromosome arm assemblies. Representation of the Y chromosome and other heterochromatic regions is particularly improved. The new 143.9-Mb reference sequence, designated Release 6, effectively exhausts clone-based technologies for mapping and sequencing. Highly repeat-rich regions, including large satellite blocks and functional elements such as the ribosomal RNA genes and the centromeres, are largely inaccessible to current sequencing and assembly methods and remain poorly represented. Further significant improvements will require sequencing technologies that do not depend on molecular cloning and that produce very long reads.

Published
2015

45. A library of MiMICs allows tagging of genes and reversible, spatial and temporal knockdown of proteins in Drosophila

Author

Nagarkar-Jaiswal, Sonal, primary, Lee, Pei-Tseng, additional, Campbell, Megan E, additional, Chen, Kuchuan, additional, Anguiano-Zarate, Stephanie, additional, Cantu Gutierrez, Manuel, additional, Busby, Theodore, additional, Lin, Wen-Wen, additional, He, Yuchun, additional, Schulze, Karen L, additional, Booth, Benjamin W, additional, Evans-Holm, Martha, additional, Venken, Koen JT, additional, Levis, Robert W, additional, Spradling, Allan C, additional, Hoskins, Roger A, additional, and Bellen, Hugo J, additional

Published
2015
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46. Author response: A library of MiMICs allows tagging of genes and reversible, spatial and temporal knockdown of proteins in Drosophila

Author

Nagarkar-Jaiswal, Sonal, primary, Lee, Pei-Tseng, additional, Campbell, Megan E, additional, Chen, Kuchuan, additional, Anguiano-Zarate, Stephanie, additional, Cantu Gutierrez, Manuel, additional, Busby, Theodore, additional, Lin, Wen-Wen, additional, He, Yuchun, additional, Schulze, Karen L, additional, Booth, Benjamin W, additional, Evans-Holm, Martha, additional, Venken, Koen JT, additional, Levis, Robert W, additional, Spradling, Allan C, additional, Hoskins, Roger A, additional, and Bellen, Hugo J, additional

Published
2015
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48. Haplotype dimorphism in a SNP collection from Drosophila melanogaster K. Teeter and M. Naeemuddin contributed equally to this work.

Author

Department of Biology, University of Michigan, Ann Arbor, Michigan 48109, Department of Biology, University of Michigan, Ann Arbor, Michigan 48109 ; Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695 ; Department of Genetics, Gardner Hall, North Carolina State University, Raleigh, NC 27695-7614, Berkeley Drosophila Genome Project, Lawrence Berkeley National Laboratory, Berkeley, California 94720, Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695, Department of Biochemistry, Stanford DNA Sequencing and Technology Center, Palo Alto, California 94306, Teeter, Katherine, Naeemuddin, Mohammed, Gasperini, Robert, Zimmerman, Erika, White, Kevin P., Hoskins, Roger, Gibson, Greg, Department of Biology, University of Michigan, Ann Arbor, Michigan 48109, Department of Biology, University of Michigan, Ann Arbor, Michigan 48109 ; Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695 ; Department of Genetics, Gardner Hall, North Carolina State University, Raleigh, NC 27695-7614, Berkeley Drosophila Genome Project, Lawrence Berkeley National Laboratory, Berkeley, California 94720, Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695, Department of Biochemistry, Stanford DNA Sequencing and Technology Center, Palo Alto, California 94306, Teeter, Katherine, Naeemuddin, Mohammed, Gasperini, Robert, Zimmerman, Erika, White, Kevin P., Hoskins, Roger, and Gibson, Greg

Abstract

A moderate resolution single nucleotide polymorphism (SNP) map of the genome of Drosophila melanogaster that is designed for use in quantitative genetic mapping is described. Seventeen approximately 500 nucleotide gene sequences spaced at 10 to 20 centimorgan intervals were combined with 49 shorter sequence tag sites (STSs) at 5 to 10 centimorgan intervals to generate a map that should not leave any gaps greater than one half of a chromosome arm when any two wild type lines are compared. Of 20 markers with sufficient polymorphism to construct haplotype cladograms, 13 showed evidence for two divergent classes of haplotype. The possible mechanisms for and implications of the unexpected finding that two thirds of all short gene sequences in D. melanogaster may be dimorphic are discussed, including the suggestion that admixture between two separate lineages may have been a major event in the history of the species. J. Exp. Zool. (Mol. Dev. Evol.) 288:63???75, 2000.?? 2000 Wiley-Liss, Inc.

Published
2006

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