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3. Optimizing substitution matrix choice and gap parameters for sequence alignment

Author

Edgar Robert C

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background While substitution matrices can readily be computed from reference alignments, it is challenging to compute optimal or approximately optimal gap penalties. It is also not well understood which substitution matrices are the most effective when alignment accuracy is the goal rather than homolog recognition. Here a new parameter optimization procedure, POP, is described and applied to the problems of optimizing gap penalties and selecting substitution matrices for pair-wise global protein alignments. Results POP is compared to a recent method due to Kim and Kececioglu and found to achieve from 0.2% to 1.3% higher accuracies on pair-wise benchmarks extracted from BALIBASE. The VTML matrix series is shown to be the most accurate on several global pair-wise alignment benchmarks, with VTML200 giving best or close to the best performance in all tests. BLOSUM matrices are found to be slightly inferior, even with the marginal improvements in the bug-fixed RBLOSUM series. The PAM series is significantly worse, giving accuracies typically 2% less than VTML. Integer rounding is found to cause slight degradations in accuracy. No evidence is found that selecting a matrix based on sequence divergence improves accuracy, suggesting that the use of this heuristic in CLUSTALW may be ineffective. Using VTML200 is found to improve the accuracy of CLUSTALW by 8% on BALIBASE and 5% on PREFAB. Conclusion The hypothesis that more accurate alignments of distantly related sequences may be achieved using low-identity matrices is shown to be false for commonly used matrix types. Source code and test data is freely available from the author's web site at http://www.drive5.com/pop.

Published
2009
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4. PILER-CR: Fast and accurate identification of CRISPR repeats

Author

Edgar Robert C

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background Sequencing of prokaryotic genomes has recently revealed the presence of CRISPR elements: short, highly conserved repeats separated by unique sequences of similar length. The distinctive sequence signature of CRISPR repeats can be found using general-purpose repeat- or pattern-finding software tools. However, the output of such tools is not always ideal for studying these repeats, and significant effort is sometimes needed to build additional tools and perform manual analysis of the output. Results We present PILER-CR, a program specifically designed for the identification and analysis of CRISPR repeats. The program executes rapidly, completing a 5 Mb genome in around 5 seconds on a current desktop computer. We validate the algorithm by manual curation and by comparison with published surveys of these repeats, finding that PILER-CR has both high sensitivity and high specificity. We also present a catalogue of putative CRISPR repeats identified in a comprehensive analysis of 346 prokaryotic genomes. Conclusion PILER-CR is a useful tool for rapid identification and classification of CRISPR repeats. The software is donated to the public domain. Source code and a Linux binary are freely available at http://www.drive5.com/pilercr.

Published
2007
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5. MUSCLE: a multiple sequence alignment method with reduced time and space complexity

Author

Edgar Robert C

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background In a previous paper, we introduced MUSCLE, a new program for creating multiple alignments of protein sequences, giving a brief summary of the algorithm and showing MUSCLE to achieve the highest scores reported to date on four alignment accuracy benchmarks. Here we present a more complete discussion of the algorithm, describing several previously unpublished techniques that improve biological accuracy and / or computational complexity. We introduce a new option, MUSCLE-fast, designed for high-throughput applications. We also describe a new protocol for evaluating objective functions that align two profiles. Results We compare the speed and accuracy of MUSCLE with CLUSTALW, Progressive POA and the MAFFT script FFTNS1, the fastest previously published program known to the author. Accuracy is measured using four benchmarks: BAliBASE, PREFAB, SABmark and SMART. We test three variants that offer highest accuracy (MUSCLE with default settings), highest speed (MUSCLE-fast), and a carefully chosen compromise between the two (MUSCLE-prog). We find MUSCLE-fast to be the fastest algorithm on all test sets, achieving average alignment accuracy similar to CLUSTALW in times that are typically two to three orders of magnitude less. MUSCLE-fast is able to align 1,000 sequences of average length 282 in 21 seconds on a current desktop computer. Conclusions MUSCLE offers a range of options that provide improved speed and / or alignment accuracy compared with currently available programs. MUSCLE is freely available at http://www.drive5.com/muscle.

Published
2004
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9. Generation of recombinant hyperimmune globulins from diverse B-cell repertoires

Author

Keating, Sheila M., Mizrahi, Rena A., Adams, Matthew S., Asensio, Michael A., Benzie, Emily, Carter, Kyle P., Chiang, Yao, Edgar, Robert C., Gautam, Bishal K., Gras, Ashley, Leong, Jackson, Leong, Renee, Lim, Yoong Wearn, Manickam, Vishal A., Medina-Cucurella, Angelica V., Niedecken, Ariel R., Saini, Jasmeen, Simons, Jan Fredrik, Spindler, Matthew J., Stadtmiller, Kacy, Tinsley, Brendan, Wagner, Ellen K., Wayham, Nicholas, Tracy, LaRee, Lundberg, Carina Vingsbo, Büscher, Dirk, Terencio, Jose Vicente, Roalfe, Lucy, Pearce, Emma, Richardson, Hayley, Goldblatt, David, Ramjag, Anushka T., Carrington, Christine V. F., Simmons, Graham, Muench, Marcus O., Chamow, Steven M., Monroe, Bryan, Olson, Charles, Oguin, Thomas H., Lynch, Heather, Jeanfreau, Robert, Mosher, Rachel A., Walch, Matthew J., Bartley, Christopher R., Ross, Carl A., Meyer, Everett H., Adler, Adam S., and Johnson, David S.

Published
2021
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10. Viroid-like colonists of human microbiomes

Author

Zheludev, Ivan N., primary, Edgar, Robert C., additional, Galiano, Maria Jose Lopez, additional, De la Peña, Marcos, additional, Babaian, Artem, additional, Bhatt, Ami S., additional, and Fire, Andrew Z., additional

Published
2024
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11. Erratum to: Stability of operational taxonomic units: an important but neglected property for analyzing microbial diversity

Author

He, Yan, Caporaso, J Gregory, Jiang, Xiao-Tao, Sheng, Hua-Fang, Huse, Susan M, Rideout, Jai Ram, Edgar, Robert C, Kopylova, Evguenia, Walters, William A, Knight, Rob, and Zhou, Hong-Wei

Subjects
Microbiology, Biological Sciences, Ecology, Medical Microbiology, Evolutionary biology
Abstract

[This corrects the article DOI: 10.1186/s40168-015-0081-x.].

Published
2015

12. Stability of operational taxonomic units: an important but neglected property for analyzing microbial diversity

Author

He, Yan, Caporaso, J Gregory, Jiang, Xiao-Tao, Sheng, Hua-Fang, Huse, Susan M, Rideout, Jai Ram, Edgar, Robert C, Kopylova, Evguenia, Walters, William A, Knight, Rob, and Zhou, Hong-Wei

Subjects
Microbiology, Biological Sciences, Ecology, Medical Microbiology, Evolutionary biology
Abstract

BackgroundThe operational taxonomic unit (OTU) is widely used in microbial ecology. Reproducibility in microbial ecology research depends on the reliability of OTU-based 16S ribosomal subunit RNA (rRNA) analyses.ResultsHere, we report that many hierarchical and greedy clustering methods produce unstable OTUs, with membership that depends on the number of sequences clustered. If OTUs are regenerated with additional sequences or samples, sequences originally assigned to a given OTU can be split into different OTUs. Alternatively, sequences assigned to different OTUs can be merged into a single OTU. This OTU instability affects alpha-diversity analyses such as rarefaction curves, beta-diversity analyses such as distance-based ordination (for example, Principal Coordinate Analysis (PCoA)), and the identification of differentially represented OTUs. Our results show that the proportion of unstable OTUs varies for different clustering methods. We found that the closed-reference method is the only one that produces completely stable OTUs, with the caveat that sequences that do not match a pre-existing reference sequence collection are discarded.ConclusionsAs a compromise to the factors listed above, we propose using an open-reference method to enhance OTU stability. This type of method clusters sequences against a database and includes unmatched sequences by clustering them via a relatively stable de novo clustering method. OTU stability is an important consideration when analyzing microbial diversity and is a feature that should be taken into account during the development of novel OTU clustering methods.

Published
2015

15. UCHIME improves sensitivity and speed of chimera detection

Author

Edgar, Robert C, Haas, Brian J, Clemente, Jose C, Quince, Christopher, and Knight, Rob

Subjects
Genetics, Biotechnology, Basic Behavioral and Social Science, Behavioral and Social Science, Algorithms, Artifacts, Computational Biology, Polymerase Chain Reaction, Sequence Analysis, DNA, Software, Mathematical Sciences, Biological Sciences, Information and Computing Sciences, Bioinformatics
Abstract

MotivationChimeric DNA sequences often form during polymerase chain reaction amplification, especially when sequencing single regions (e.g. 16S rRNA or fungal Internal Transcribed Spacer) to assess diversity or compare populations. Undetected chimeras may be misinterpreted as novel species, causing inflated estimates of diversity and spurious inferences of differences between populations. Detection and removal of chimeras is therefore of critical importance in such experiments.ResultsWe describe UCHIME, a new program that detects chimeric sequences with two or more segments. UCHIME either uses a database of chimera-free sequences or detects chimeras de novo by exploiting abundance data. UCHIME has better sensitivity than ChimeraSlayer (previously the most sensitive database method), especially with short, noisy sequences. In testing on artificial bacterial communities with known composition, UCHIME de novo sensitivity is shown to be comparable to Perseus. UCHIME is >100× faster than Perseus and >1000× faster than ChimeraSlayer.Contactrobert@drive5.comAvailabilitySource, binaries and data: http://drive5.com/uchime.Supplementary informationSupplementary data are available at Bioinformatics online.

Published
2011

16. Extant hybrids of RNA viruses and viroid-like elements

Author

Forgia, Marco, primary, Navarro, Beatriz, additional, Daghino, Stefania, additional, Cervera, Amelia, additional, Gisel, Andreas, additional, Perotto, Silvia, additional, Aghayeva, Dilzara N., additional, Akinyuwa, Mary Funmilayo, additional, Gobbi, Emanuela, additional, Zheludev, Ivan N., additional, Edgar, Robert C., additional, Chikhi, Rayan, additional, Turina, Massimo, additional, Babaian, Artem, additional, Serio, Francesco Di, additional, and de la Peña, Marcos, additional

Published
2022
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18. GMP Manufacturing and IND-Enabling Studies of a Recombinant Hyperimmune Globulin Targeting SARS-CoV-2

Author

Mizrahi, Rena A., primary, Lin, Wendy Y., additional, Gras, Ashley, additional, Niedecken, Ariel R., additional, Wagner, Ellen K., additional, Keating, Sheila M., additional, Ikon, Nikita, additional, Manickam, Vishal A., additional, Asensio, Michael A., additional, Leong, Jackson, additional, Medina-Cucurella, Angelica V., additional, Benzie, Emily, additional, Carter, Kyle P., additional, Chiang, Yao, additional, Edgar, Robert C., additional, Leong, Renee, additional, Lim, Yoong Wearn, additional, Simons, Jan Fredrik, additional, Spindler, Matthew J., additional, Stadtmiller, Kacy, additional, Wayham, Nicholas, additional, Büscher, Dirk, additional, Terencio, Jose Vicente, additional, Germanio, Clara Di, additional, Chamow, Steven M., additional, Olson, Charles, additional, Pino, Paula A., additional, Park, Jun-Gyu, additional, Hicks, Amberlee, additional, Ye, Chengjin, additional, Garcia-Vilanova, Andreu, additional, Martinez-Sobrido, Luis, additional, Torrelles, Jordi B., additional, Johnson, David S., additional, and Adler, Adam S., additional

Published
2022
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21. Defining the core Arabidopsis thaliana root microbiome

Author

Lundberg, Derek S., Lebeis, Sarah L., Paredes, Sur Herrera, Yourstone, Scott, Gehring, Jase, Malfatti, Stephanie, Tremblay, Julien, Engelbrektson, Anna, Kunin, Victor, Rio, Tijana Glavinadel, Edgar, Robert C., Eickhorst, Thilo, Ley, Ruth E., Hugenholtz, Philip, Tringe, Susannah Green, and Dang, Jeffery L.

Subjects
Microbiota (Symbiotic organisms) -- Observations -- Research -- Genetic aspects, RNA sequencing -- Research -- Genetic aspects, Arabidopsis thaliana -- Genetic aspects -- Research, Host-bacteria relationships -- Observations -- Genetic aspects -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Land plants associate with a root microbiota distinct from the complex microbial community present in surrounding soil. The microbiota colonizing the rhizosphere (immediately surrounding the root) and the endophytic compartment (within the root) contribute to plant growth, productivity, carbon sequestration and phytoremediation (1-3). Colonization of the root occurs despite a sophisticated plant immune system (4,5), suggesting finely tuned discrimination of mutualists and commensals from pathogens. Genetic principles governing the derivation of host-specific endophyte communities from soil communities are poorly understood. Here we report the pyrosequencing of the bacterial 16S ribosomal RNA gene of more than 600 Arabidopsis thaliana plants to test the hypotheses that the root rhizosphere and endophytic compartment microbiota of plants grown under controlled conditions in natural soils are sufficiently dependent on the host to remain consistent across different soil types and developmental stages, and sufficiently dependent on host genotype to vary between inbred Arabidopsis accessions. We describe different bacterial communities in two geochemically distinct bulk soils and in rhizosphere and endophytic compartments prepared from roots grown in these soils. The communities in each compartment are strongly influenced by soil type. Endophytic compartments from both soils feature overlapping, low-complexity communities that are markedly enriched in Actinobacteria and specific families from other phyla, notably Proteobacteria. Some bacteria vary quantitatively between plants of different developmental stage and genotype. Our rigorous definition of an endophytic compartment microbiome should facilitate controlled dissection of plant-microbe interactions derived from complex soil communities., Roots influence the rhizosphere by altering soil pH, soil structure, oxygen availability, antimicrobial concentration, and quorum-sensing mimicry, and by providing an energy source of dead root material and carbon-rich exudates [...]

Published
2013

23. Defining the core Arabidopsis thaliana root microbiome

Author

Lundberg, Derek S., Lebeis, Sarah L., Paredes, Sur Herrera, Yourstone, Scott, Gehring, Jase, Malfatti, Stephanie, Tremblay, Julien, Engelbrektson, Anna, Kunin, Victor, del Rio, Tijana Glavina, Edgar, Robert C., Eickhorst, Thilo, Ley, Ruth E., Hugenholtz, Philip, Tringe, Susannah Green, and Dangl, Jeffery L.

Subjects
Symbiosis -- Research, Arabidopsis -- Physiological aspects -- Health aspects, Microbial colonies -- Physiological aspects -- Health aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Land plants associate with a root microbiota distinct from the complex microbial community present in surrounding soil. The microbiota colonizing the rhizosphere (immediately surrounding the root) and the endophytic compartment [...]

Published
2012

25. A framework for human microbiome research

Author

Methé, Barbara A., Nelson, Karen E., Pop, Mihai, Creasy, Heather H., Giglio, Michelle G., Huttenhower, Curtis, Gevers, Dirk, Petrosino, Joseph F., Abubucker, Sahar, Badger, Jonathan H., Chinwalla, Asif T., Earl, Ashlee M., FitzGerald, Michael G., Fulton, Robert S., Hallsworth-Pepin, Kymberlie, Lobos, Elizabeth A., Madupu, Ramana, Magrini, Vincent, Martin, John C., Mitreva, Makedonka, Muzny, Donna M., Sodergren, Erica J., Versalovic, James, Wollam, Aye M., Worley, Kim C., Wortman, Jennifer R., Young, Sarah K., Zeng, Qiandong, Aagaard, Kjersti M., Abolude, Olukemi O., Allen-Vercoe, Emma, Alm, Eric J., Alvarado, Lucia, Andersen, Gary L., Anderson, Scott, Appelbaum, Elizabeth, Arachchi, Harindra M., Armitage, Gary, Arze, Cesar A., Ayvaz, Tulin, Baker, Carl C., Begg, Lisa, Belachew, Tsegahiwot, Bhonagiri, Veena, Bihan, Monika, Blaser, Martin J., Bloom, Toby, Bonazzi, Vivien R., Brooks, Paul, Buck, Gregory A., Buhay, Christian J., Busam, Dana A., Campbell, Joseph L., Canon, Shane R., Cantarel, Brandi L., Chain, Patrick S., Chen, I-Min A., Chen, Lei, Chhibba, Shaila, Chu, Ken, Ciulla, Dawn M., Clemente, Jose C., Clifton, Sandra W., Conlan, Sean, Crabtree, Jonathan, Cutting, Mary A., Davidovics, Noam J., Davis, Catherine C., DeSantis, Todd Z., Deal, Carolyn, Delehaunty, Kimberley D., Dewhirst, Floyd E., Deych, Elena, Ding, Yan, Dooling, David J., Dugan, Shannon P., Dunne, Michael W., Jr, Durkin, Scott A., Edgar, Robert C., Erlich, Rachel L., Farmer, Candace N., Farrell, Ruth M., Faust, Karoline, Feldgarden, Michael, Felix, Victor M., Fisher, Sheila, Fodor, Anthony A., Forney, Larry, Foster, Leslie, Di Francesco, Valentina, Friedman, Jonathan, Friedrich, Dennis C., Fronick, Catrina C., Fulton, Lucinda L., Gao, Hongyu, Garcia, Nathalia, Giannoukos, Georgia, Giblin, Christina, Giovanni, Maria Y., Goldberg, Jonathan M., Goll, Johannes, Gonzalez, Antonio, Griggs, Allison, Gujja, Sharvari, Haas, Brian J., Hamilton, Holli A., Harris, Emily L., Hepburn, Theresa A., Herter, Brandi, Hoffmann, Diane E., Holder, Michael E., Howarth, Clinton, Huang, Katherine H., Huse, Susan M., Izard, Jacques, Jansson, Janet K., Jiang, Huaiyang, Jordan, Catherine, Joshi, Vandita, Katancik, James A., Keitel, Wendy A., Kelley, Scott T., Kells, Cristyn, Kinder-Haake, Susan, King, Nicholas B., Knight, Rob, Knights, Dan, Kong, Heidi H., Koren, Omry, Koren, Sergey, Kota, Karthik C., Kovar, Christie L., Kyrpides, Nikos C., La Rosa, Patricio S., Lee, Sandra L., Lemon, Katherine P., Lennon, Niall, Lewis, Cecil M., Lewis, Lora, Ley, Ruth E., Li, Kelvin, Liolios, Konstantinos, Liu, Bo, Liu, Yue, Lo, Chien-Chi, Lozupone, Catherine A., Lunsford, Dwayne R., Madden, Tessa, Mahurkar, Anup A., Mannon, Peter J., Mardis, Elaine R., Markowitz, Victor M., Mavrommatis, Konstantinos, McCorrison, Jamison M., McDonald, Daniel, McEwen, Jean, McGuire, Amy L., McInnes, Pamela, Mehta, Teena, Mihindukulasuriya, Kathie A., Miller, Jason R., Minx, Patrick J., Newsham, Irene, Nusbaum, Chad, O’Laughlin, Michelle, Orvis, Joshua, Pagani, Ioanna, Palaniappan, Krishna, Patel, Shital M., Pearson, Matthew, Peterson, Jane, Podar, Mircea, Pohl, Craig, Pollard, Katherine S., Priest, Margaret E., Proctor, Lita M., Qin, Xiang, Raes, Jeroen, Ravel, Jacques, Reid, Jeffrey G., Rho, Mina, Rhodes, Rosamond, Riehle, Kevin P., Rivera, Maria C., Rodriguez-Mueller, Beltran, Rogers, Yu-Hui, Ross, Matthew C., Russ, Carsten, Sanka, Ravi K., Sankar, Pamela, Sathirapongsasuti, Fah J., Schloss, Jeffery A., Schloss, Patrick D., Schmidt, Thomas M., Scholz, Matthew, Schriml, Lynn, Schubert, Alyxandria M., Segata, Nicola, Segre, Julia A., Shannon, William D., Sharp, Richard R., Sharpton, Thomas J., Shenoy, Narmada, Sheth, Nihar U., Simone, Gina A., Singh, Indresh, Smillie, Chris S., Sobel, Jack D., Sommer, Daniel D., Spicer, Paul, Sutton, Granger G., Sykes, Sean M., Tabbaa, Diana G., Thiagarajan, Mathangi, Tomlinson, Chad M., Torralba, Manolito, Treangen, Todd J., Truty, Rebecca M., Vishnivetskaya, Tatiana A., Walker, Jason, Wang, Lu, Wang, Zhengyuan, Ward, Doyle V., Warren, Wesley, Watson, Mark A., Wellington, Christopher, Wetterstrand, Kris A., White, James R., Wilczek-Boney, Katarzyna, Wu, Yuan Qing, Wylie, Kristine M., Wylie, Todd, Yandava, Chandri, Ye, Liang, Ye, Yuzhen, Yooseph, Shibu, Youmans, Bonnie P., Zhang, Lan, Zhou, Yanjiao, Zhu, Yiming, Zoloth, Laurie, Zucker, Jeremy D., Birren, Bruce W., Gibbs, Richard A., Highlander, Sarah K., Weinstock, George M., Wilson, Richard K., and White, Owen

Published
2012
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26. Structure, function and diversity of the healthy human microbiome

Author

Huttenhower, Curtis, Gevers, Dirk, Knight, Rob, Abubucker, Sahar, Badger, Jonathan H., Chinwalla, Asif T., Creasy, Heather H., Earl, Ashlee M., FitzGerald, Michael G., Fulton, Robert S., Giglio, Michelle G., Hallsworth-Pepin, Kymberlie, Lobos, Elizabeth A., Madupu, Ramana, Magrini, Vincent, Martin, John C., Mitreva, Makedonka, Muzny, Donna M., Sodergren, Erica J., Versalovic, James, Wollam, Aye M., Worley, Kim C., Wortman, Jennifer R., Young, Sarah K., Zeng, Qiandong, Aagaard, Kjersti M., Abolude, Olukemi O., Allen-Vercoe, Emma, Alm, Eric J., Alvarado, Lucia, Andersen, Gary L., Anderson, Scott, Appelbaum, Elizabeth, Arachchi, Harindra M., Armitage, Gary, Arze, Cesar A., Ayvaz, Tulin, Baker, Carl C., Begg, Lisa, Belachew, Tsegahiwot, Bhonagiri, Veena, Bihan, Monika, Blaser, Martin J., Bloom, Toby, Bonazzi, Vivien, Brooks, Paul J., Buck, Gregory A., Buhay, Christian J., Busam, Dana A., Campbell, Joseph L., Canon, Shane R., Cantarel, Brandi L., Chain, Patrick S. G., Chen, I-Min A., Chen, Lei, Chhibba, Shaila, Chu, Ken, Ciulla, Dawn M., Clemente, Jose C., Clifton, Sandra W., Conlan, Sean, Crabtree, Jonathan, Cutting, Mary A., Davidovics, Noam J., Davis, Catherine C., DeSantis, Todd Z., Deal, Carolyn, Delehaunty, Kimberley D., Dewhirst, Floyd E., Deych, Elena, Ding, Yan, Dooling, David J., Dugan, Shannon P., Dunne, Wm Michael, Durkin, Scott A., Edgar, Robert C., Erlich, Rachel L., Farmer, Candace N., Farrell, Ruth M., Faust, Karoline, Feldgarden, Michael, Felix, Victor M., Fisher, Sheila, Fodor, Anthony A., Forney, Larry J., Foster, Leslie, Di Francesco, Valentina, Friedman, Jonathan, Friedrich, Dennis C., Fronick, Catrina C., Fulton, Lucinda L., Gao, Hongyu, Garcia, Nathalia, Giannoukos, Georgia, Giblin, Christina, Giovanni, Maria Y., Goldberg, Jonathan M., Goll, Johannes, Gonzalez, Antonio, Griggs, Allison, Gujja, Sharvari, Haake, Susan Kinder, Haas, Brian J., Hamilton, Holli A., Harris, Emily L., Hepburn, Theresa A., Herter, Brandi, Hoffmann, Diane E., Holder, Michael E., Howarth, Clinton, Huang, Katherine H., Huse, Susan M., Izard, Jacques, Jansson, Janet K., Jiang, Huaiyang, Jordan, Catherine, Joshi, Vandita, Katancik, James A., Keitel, Wendy A., Kelley, Scott T., Kells, Cristyn, King, Nicholas B., Knights, Dan, Kong, Heidi H., Koren, Omry, Koren, Sergey, Kota, Karthik C., Kovar, Christie L., Kyrpides, Nikos C., La Rosa, Patricio S., Lee, Sandra L., Lemon, Katherine P., Lennon, Niall, Lewis, Cecil M., Lewis, Lora, Ley, Ruth E., Li, Kelvin, Liolios, Konstantinos, Liu, Bo, Liu, Yue, Lo, Chien-Chi, Lozupone, Catherine A., Lunsford, Dwayne R., Madden, Tessa, Mahurkar, Anup A., Mannon, Peter J., Mardis, Elaine R., Markowitz, Victor M., Mavromatis, Konstantinos, McCorrison, Jamison M., McDonald, Daniel, McEwen, Jean, McGuire, Amy L., McInnes, Pamela, Mehta, Teena, Mihindukulasuriya, Kathie A., Miller, Jason R., Minx, Patrick J., Newsham, Irene, Nusbaum, Chad, O’Laughlin, Michelle, Orvis, Joshua, Pagani, Ioanna, Palaniappan, Krishna, Patel, Shital M., Pearson, Matthew, Peterson, Jane, Podar, Mircea, Pohl, Craig, Pollard, Katherine S., Pop, Mihai, Priest, Margaret E., Proctor, Lita M., Qin, Xiang, Raes, Jeroen, Ravel, Jacques, Reid, Jeffrey G., Rho, Mina, Rhodes, Rosamond, Riehle, Kevin P., Rivera, Maria C., Rodriguez-Mueller, Beltran, Rogers, Yu-Hui, Ross, Matthew C., Russ, Carsten, Sanka, Ravi K., Sankar, Pamela, Sathirapongsasuti, Fah J., Schloss, Jeffery A., Schloss, Patrick D., Schmidt, Thomas M., Scholz, Matthew, Schriml, Lynn, Schubert, Alyxandria M., Segata, Nicola, Segre, Julia A., Shannon, William D., Sharp, Richard R., Sharpton, Thomas J., Shenoy, Narmada, Sheth, Nihar U., Simone, Gina A., Singh, Indresh, Smillie, Christopher S., Sobel, Jack D., Sommer, Daniel D., Spicer, Paul, Sutton, Granger G., Sykes, Sean M., Tabbaa, Diana G., Thiagarajan, Mathangi, Tomlinson, Chad M., Torralba, Manolito, Treangen, Todd J., Truty, Rebecca M., Vishnivetskaya, Tatiana A., Walker, Jason, Wang, Lu, Wang, Zhengyuan, Ward, Doyle V., Warren, Wesley, Watson, Mark A., Wellington, Christopher, Wetterstrand, Kris A., White, James R., Wilczek-Boney, Katarzyna, Wu, YuanQing, Wylie, Kristine M., Wylie, Todd, Yandava, Chandri, Ye, Liang, Ye, Yuzhen, Yooseph, Shibu, Youmans, Bonnie P., Zhang, Lan, Zhou, Yanjiao, Zhu, Yiming, Zoloth, Laurie, Zucker, Jeremy D., Birren, Bruce W., Gibbs, Richard A., Highlander, Sarah K., Methé, Barbara A., Nelson, Karen E., Petrosino, Joseph F., Weinstock, George M., Wilson, Richard K., and White, Owen

Published
2012
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28. Petabase-scale sequence alignment catalyses viral discovery

Author

Edgar, Robert C., primary, Taylor, Jeff, additional, Lin, Victor, additional, Altman, Tomer, additional, Barbera, Pierre, additional, Meleshko, Dmitry, additional, Lohr, Dan, additional, Novakovsky, Gherman, additional, Buchfink, Benjamin, additional, Al-Shayeb, Basem, additional, Banfield, Jillian F., additional, de la Peña, Marcos, additional, Korobeynikov, Anton, additional, Chikhi, Rayan, additional, and Babaian, Artem, additional

Published
2020
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29. Capturing and Recreating Diverse Antibody Repertoires as Multivalent Recombinant Polyclonal Antibody Drugs

Author

Keating, Sheila M., primary, Mizrahi, Rena A., additional, Adams, Matthew S., additional, Asensio, Michael A., additional, Benzie, Emily, additional, Carter, Kyle P., additional, Chiang, Yao, additional, Edgar, Robert C., additional, Gautam, Bishal K., additional, Gras, Ashley, additional, Leong, Jackson, additional, Leong, Renee, additional, Lim, Yoong Wearn, additional, Manickam, Vishal A., additional, Medina-Cucurella, Angelica V., additional, Niedecken, Ariel R., additional, Saini, Jasmeen, additional, Simons, Jan Fredrik, additional, Spindler, Matthew J., additional, Stadtmiller, Kacy, additional, Tinsley, Brendan, additional, Wagner, Ellen K., additional, Wayham, Nicholas, additional, Tracy, LaRee, additional, Lundberg, Carina Vingsbo, additional, Büscher, Dirk, additional, Terencio, Jose Vicente, additional, Roalfe, Lucy, additional, Pearce, Emma, additional, Richardson, Hayley, additional, Goldblatt, David, additional, Ramjag, Anushka T., additional, Carrington, Christine V.F., additional, Simmons, Graham, additional, Muench, Marcus O., additional, Chamow, Steven M., additional, Monroe, Bryan, additional, Olson, Charles, additional, Oguin, Thomas H., additional, Lynch, Heather, additional, Jeanfreau, Robert, additional, Meyer, Everett H., additional, Adler, Adam S., additional, and Johnson, David S., additional

Published
2020
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33. The Genome Sequence of Taurine Cattle: A Window to Ruminant Biology and Evolution

Author

Elsik, Christine G., Tellam, Ross L., Worley, Kim C., Gibbs, Richard A., Elsik, Christine G., Tellam, Ross L, Gibbs, Richard A., Muzny, Donna M., Weinstock, George M., Adelson, David L, Eichler, Evan E., Elnitski, Laura, Elsik, Christine G., Guigó, Roderic, Hamernik, Debora L., Kappes, Steve M., Lewin, Harris A, Lynn, David J., Nicholas, Frank W., Reymond, Alexandre, Rijnkels, Monique, Skow, Loren C., Tellam, Ross L, Worley, Kim C., Zdobnov, Evgeny M., Gibbs, Richard A., Kappes, Steve M., Schook, Lawrence, Skow, Loren C., Weinstock, George M., Womack, James, Alioto, Tyler, Antonarakis, Stylianos E., Astashyn, Alex, Chapple, Charles E., Chen, Hsiu-Chuan, Chrast, Jacqueline, Câmara, Francisco, Elsik, Christine G., Ermolaeva, Olga, Guigó, Roderic, Henrichsen, Charlotte N., Hlavina, Wratko, Kapustin, Yuri, Kiryutin, Boris, Kitts, Paul, Kokocinski, Felix, Landrum, Melissa, Maglott, Donna, Pruitt, Kim, Reymond, Alexandre, Sapojnikov, Victor, Searle, Stephen M., Solovyev, Victor, Souvorov, Alexandre, Ucla, Catherine, Weinstock, George M., Wyss, Carine, Alioto, Tyler, Antonarakis, Stylianos E., Chapple, Charles E., Chrast, Jacqueline, Câmara, Francisco, Guigó, Roderic, Henrichsen, Charlotte N., Reymond, Alexandre, Ucla, Catherine, Wyss, Carine, Anzola, Juan M., Gerlach, Daniel, Zdobnov, Evgeny M., Elhaik, Eran, Elsik, Christine G., Graur, Dan, Reese, Justin T., Adelson, David L., Edgar, Robert C., McEwan, John C., Payne, Gemma M., Raison, Joy M., Junier, Thomas, Kriventseva, Evgenia V., Zdobnov, Evgeny M., Chrast, Jacqueline, Eyras, Eduardo, Henrichsen, Charlotte N., Plass, Mireya, Reymond, Alexandre, Donthu, Ravikiran, Larkin, Denis M., Lewin, Harris A., Nicholas, Frank W., Elnitski, Laura, Larkin, Denis M., Lewin, Harris A., Reecy, James, Yang, Mary Q., Adelson, David L, Chen, Lin, Cheng, Ze, Chitko-McKown, Carol G., Eichler, Evan E., Elnitski, Laura, Elsik, Christine G., Liu, George E., Matukumalli, Lakshmi K., Song, Jiuzhou, Zhu, Bin, Elsik, Christine G., Lynn, David J., Reese, Justin T., Bradley, Daniel G., Brinkman, Fiona S.L, Lau, Lilian P.L., Lynn, David J., Whiteside, Matthew D., Tellam, Ross L, Walker, Angela, Wheeler, Thomas T., Casey, Theresa, German, Bruce J., Lemay, Danielle G., Lynn, David J., Maqbool, Nauman J., Molenaar, Adrian J., Rijnkels, Monique, Lewin, Harris A., Seo, Seongwon, Stothard, Paul, Baldwin, Cynthia L., Baxter, Rebecca, Brinkmeyer-Langford, Candice L., Brown, Wendy C., Childers, Christopher P., Connelley, Timothy, Ellis, Shirley A., Fritz, Krista, Glass, Elizabeth J., Herzig, Carolyn T.A., livanainen, Antti, Lahmers, Kevin K., Skow, Loren C., Bennett, Anna K., Childers, Christopher P., Dickens, Michael C., Elsik, Christine G., Gilbert, James G.R., Hagen, Darren E., Reese, Justin T., Salih, Hanni, Aerts, Jan, Caetano, Alexandre R., Dalrymple, Brian, Elsik, Christine G., Fernando Garcia, Jose, Gibbs, Richard A., Gill, Clare A., Hamernik, Debora L, Hiendleder, Stefan G., Memili, Erdogan, Nicholas, Frank W., Reecy, James, Rijnkels, Monique, Skow, Loren C., Spurlock, Diane, Stothard, Paul, Tellam, Ross L, Weinstock, George M., Williams, John L, Worley, Kim C., Alexander, Lee, Brownstein, Michael J., Guan, Leluo, Holt, Robert A., Jones, Steven J.M., Marra, Marco A., Moore, Richard, Moore, Stephen S., Roberts, Andy, Taniguchi, Masaaki, Waterman, Richard C., Chacko, Joseph, Chandrabose, Mimi M., Cree, Andy, Diep Dao, Marvin, Dinh, Huyen H., Ayiesha Gabisi, Ramatu, Hines, Sandra, Hume, Jennifer, Jhangiani, Shalini N., Joshi, Vandita, Kovar, Christie L., Lewis, Lora R., Liu, Yih-shin, Lopez, John, Morgan, Margaret B., Muzny, Donna M., Bich Nguyen, Ngoc, Okwuonu, Geoffrey O., Ruiz, San Juana, Santibanez, Jireh, Wright, Rita A., Buhay, Christian, Ding, Yan, Dugan-Rocha, Shannon, Herdandez, Judith, Holder, Michael, Sabo, Aniko, Egan, Amy, Goodell, Jason, Wilczek-Boney, Katarzyna, Fowler, Gerald R., Edward Hitchens, Matthew, Lozado, Ryan J., Moen, Charles, Steffen, David, Warren, James T., Zhang, Jingkun, Chiu, Readman, Jones, Steven J.M., Marra, Marco A., Schein, Jacqueline E., James Durbin, K., Havlak, Paul, Jiang, Huaiyang, Liu, Yue, Qin, Xiang, Ren, Yanru, Shen, Yufeng, Song, Henry, Weinstock, George M., Worley, Kim C., Nicole Bell, Stephanie, Davis, Clay, Jolivet Johnson, Angela, Lee, Sandra, Nazareth, Lynne V., Patel, Bella Mayurkumar, Pu, Ling-Ling, Vattathil, Selina, Williams, Rex Lee, Jr., Curry, Stacey, Hamilton, Cerissa, Sodergren, Erica, Nazareth, Lynne V., Wheeler, David A., Adelson, David L, Aerts, Jan, Barris, Wes, Bennett, Gary L, Dalrymple, Brian, Eggen, André, Gill, Clare A., Green, Ronnie D., Harhay, Gregory P., Hobbs, Matthew, Jann, Oliver, Kappes, Steve M., Keele, John W., Kent, Matthew P., Larkin, Denis M., Lewin, Harris A., Lien, Sigbjørn, McEwan, John C., McKay, Stephanie D., McWilliam, Sean, Moore, Stephen S., Nicholas, Frank W., Payne, Gemma M., Ratnakumar, Abhirami, Salih, Hanni, Schnabel, Robert D., Smith, Timothy, Snelling, Warren M., Sonstegard, Tad S., Stone, Roger T., Sugimoto, Yoshikazu, Takasuga, Akiko, Taylor, Jeremy F., Tellam, Ross L., Van Tassell, Curtis P., Williams, John L, MacNeil, Michael D., Abatepaulo, Antonio R.R., Abbey, Colette A., Aerts, Jan, Ahola, Virpi, Almeida, Iassudara G., Amadio, Ariel F., Anatriello, Elen, Bahadue, Suria M., Baldwin, Cynthia L., Baxter, Rebecca, Bennett, Anna K., Biase, Fernando H., Boldt, Clayton R., Brinkmeyer-Langford, Candice L, Brown, Wendy C., Caetano, Alexandre R., Carroll, Jeffery A., Carvalho, Wanessa A, Casey, Theresa, Cervelatti, Eliane P., Chacko, Elsa, Chapin, Jennifer E., Cheng, Ye, Childers, Christopher P., Choi, Jungwoo, Colley, Adam J., Connelley, Timothy, de Campos, Tatiana A., De Donato, Marcos, de Miranda Santos, Isabel K.F., de Oliveira, Carlo J.F., Deobald, Heather, Devinoy, Eve, Dickens, Michael C., Donohue, Kaitlin E., Dovc, Peter, Eberlein, Annett, Ellis, Shirley A., Fitzsimmons, Carolyn J., Franzin, Alessandra M., Fritz, Krista, Garcia, Gustavo R., Fernando Garcia, Jose, Genini, Sem, German, Bruce J., Gilbert, James G.R., Gill, Clare A., Gladney, Cody J., Glass, Elizabeth J., Grant, Jason R., Greaser, Marion L., Green, Jonathan A., Hadsell, Darryl L., Hagen, Darren E., Hakimov, Hatam A., Halgren, Rob, Harrow, Jennifer L, Hart, Elizabeth A., Hastings, Nicola, Hernandez, Marta, Herzig, Carolyn T.A., Hiendleder, Stefan G., Hobbs, Matthew, Hu, Zhi-Liang, livanainen, Antti, Ingham, Aaron, Iso-Touru, Terhi, Jamis, Catherine, Jann, Oliver, Jensen, Kirsty, Kapetis, Dimos, Kerr, Tovah, Khalil, Sari S., Khatib, Hasan, Kolbehdari, Davood, Kumar, Charu G., Kumar, Dinesh, Leach, Richard, Lee, Justin C-M, Lemay, Danielle G., Li, Changxi, Liu, George E., Logan, Krystin M., Malinverni, Roberto, Maqbool, Nauman J., Marques, Elisa, Martin, William F., Martins, Natalia F., Maruyama, Sandra R., Mazza, Raffaele, McLean, Kim L, Medrano, Juan F., Memili, Erdogan, Molenaar, Adrian J., Moreno, Barbara T., Moré, Daniela D., Muntean, Carl T., Nandakumar, Hari P., Nogueira, Marcelo F.G., Olsaker, Ingrid, Pant, Sameer D., Panzitta, Francesca, Pastor, Rosemeire C.P., Poli, Mario A., Poslusny, Nathan, Rachagani, Satyanarayana, Ranganathan, Shoba, Razpet, Andrej, Reecy, James, Riggs, Penny K., Rijnkels, Monique, Rincon, Gonzalo, Rodriguez-Osorio, Nelida, Rodriguez-Zas, Sandra L., Romero, Natasha E., Rosenwald, Anne, Sando, Lillian, Schmutz, Sheila M., Seo, Seongwon, Shen, Libing, Sherman, Laura, Skow, Loren C., Southey, Bruce R., Spurlock, Diane, Strandberg Lutzow, Ylva, Sweedler, Jonathan V., Tammen, Imke, Taniguchi, Masaaki, Tellam, Ross L, Telugu, Bhanu Prakash V.L, Urbanski, Jennifer M., Utsunomiya, Yuri T., Verschoor, Chris P., Waardenberg, Ashley J., Walker, Angela, Wang, Zhiquan, Ward, Robert, Weikard, Rosemarie, Welsh, Thomas H., Jr., Wheeler, Thomas T., White, Stephen N., Williams, John L, Wilming, Laurens G., Wunderlich, Kris R., Yang, Jianqi, and Zhao, Feng-Qi

Published
2009

41. URMAP, an ultra-fast read mapper

Author

Edgar, Robert C.

Subjects
Bioinformatics, Computer science, lcsh:Medicine, General Biochemistry, Genetics and Molecular Biology, Computational science, 03 medical and health sciences, 0302 clinical medicine, Software, Next generation sequencing, Mapping algorithm, Ultra fast, Sensitivity (control systems), Molecular Biology, 030304 developmental biology, 0303 health sciences, Biological studies, business.industry, General Neuroscience, lcsh:R, Computational Biology, Pattern recognition, General Medicine, Repetitive Regions, Fast mapping, Benchmark (computing), Human genome, Read mapping, Artificial intelligence, General Agricultural and Biological Sciences, business, 030217 neurology & neurosurgery, Large size
Abstract

Mapping of reads to reference sequences is an essential step in a wide range of biological studies. The large size of datasets generated with next-generation sequencing technologies motivates the development of fast mapping software. Here, I describe URMAP, a new read mapping algorithm. URMAP is an order of magnitude faster than BWA with comparable accuracy on several validation tests. On a Genome in a Bottle (GIAB) variant calling test with 30× coverage 2×150 reads, URMAP achieves high accuracy (precision 0.998, sensitivity 0.982 and F-measure 0.990) with the strelka2 caller. However, GIAB reference variants are shown to be biased against repetitive regions which are difficult to map and may therefore pose an unrealistically easy challenge to read mappers and variant callers.

Published
2020

42. Antibody repertoire analysis of mouse immunization protocols using microfluidics and molecular genomics

Author

Asensio, Michael A., primary, Lim, Yoong Wearn, additional, Wayham, Nicholas, additional, Stadtmiller, Kacy, additional, Edgar, Robert C., additional, Leong, Jackson, additional, Leong, Renee, additional, Mizrahi, Rena A., additional, Adams, Matthew S., additional, Simons, Jan Fredrik, additional, Spindler, Matthew J., additional, Johnson, David S., additional, and Adler, Adam S., additional

Published
2019
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43. Octave plots for visualizing diversity of microbial OTUs

Author

Edgar, Robert C., Flyvbjerg, Henrik, Edgar, Robert C., and Flyvbjerg, Henrik

Abstract

Next-generation sequencing of marker genes such as 16S ribosomal RNA is widely used to survey microbial communities. The abundance distribution (AD) of Operational Taxonomic Units (OTUs) in a sample is typically summarized by alpha diversity metrics, e.g. richness and entropy, discarding information about the AD shape. In this work, we describe octave plots, histograms which visualize the shape of microbial ADs by binning on a logarithmic scale with base 2. Optionally, histogram bars are colored to indicate possible spurious OTUs due to sequence error and cross-talk. Octave plots enable assessment of (a) the shape and completeness of the distribution, (b) the effects of noise on measured diversity, (c) whether low-abundance OTUs should be discarded, (d) whether alpha diversity metrics and estimators are reliable, and (e) the additional sampling effort (i.e., read depth) required to obtain a complete census of the community. The utility of octave plots is illustrated in a re-analysis of a prostate cancer study showing that the reported core microbiome is most likely an artifact of experimental error.

Published
2018

44. Alpha diversity metrics for noisy OTUs

Author

Edgar, Robert C., Flyvbjerg, Henrik, Edgar, Robert C., and Flyvbjerg, Henrik

Abstract

Next-generation sequencing (NGS) of marker genes such as 16S ribosomal RNA is widely used to survey microbial communities. The in-sample (alpha) diversity of Operational Taxonomic Units (OTUs) is often summarized by metrics such as richness or entropy which are calculated from observed abundances, or by estimators such as Chao1 which extrapolate to unobserved OTUs. Most such measures are adopted from traditional biodiversity studies, where observational error can often be neglected. However, errors introduced by next-generation amplicon sequencing tend to induce spurious OTUs and spurious counts in OTU tables, both of which are especially prevalent at low abundances. In consequence, traditional metrics may be grossly inaccurate if they are naively applied to NGS OTU tables. In this work, we describe two novel alpha diversity estimators which are calculated from OTU abundances above a specified threshold. The singleton-free estimator (SFE) is a non-parametric estimator which is derived from a similar approach to Chao1 but extrapolates using doublet and triplet abundances rather than singletons and doublets. The octave estimator (OE) fits a log-normal distribution to non-singleton bars of an octave plot. We show that these estimators are effective under suitable conditions, but these conditions rarely apply in practice. We conclude that extrapolating to unobserved OTUs remains an open problem which is unlikely to be solved in the near future.

Published
2018

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