Selected publications using Galaxy-P

Below is a selection of publications describing the development and application of the Galaxy-P platform.  For an updated list of all publications describing work enabled by the Galaxy-P platform, see this link.

2023

Metaproteomic Analysis of Nasopharyngeal Swab Samples to Identify Microbial Peptides in COVID-19 Patients. Bihani S, Gupta A, Mehta S, Rajczewski AT, Johnson J, Borishetty D, Griffin TJ, Srivastava S, Jagtap PD. J Proteome Res. 2023 Aug 4;22(8):2608-2619. doi: 10.1021/acs.jproteome.3c00040. Epub 2023 Jul 14. PMID: 37450889.

Integrative meta-omics in Galaxy and beyond. Schiml VC, Delogu F, Kumar P, Kunath B, Batut B, Mehta S, Johnson JE, Grüning B, Pope PB, Jagtap PD, Griffin TJ, Arntzen MØ. Environ Microbiome. 2023 Jul 7;18(1):56. Doi: 10.1186/s40793-023-00514-9. PMID: 37420292; PMCID: PMC10329324.

Galaxy Training: A powerful framework for teaching! Hiltemann S, Rasche H, Gladman S, Hotz HR, Larivière D, Blankenberg D, Jagtap PD, Wollmann T, Bretaudeau A, Goué N, Griffin TJ, Royaux C, Le Bras Y, Mehta S, Syme A, Coppens F, Droesbeke B, Soranzo N, Bacon W, Psomopoulos F, Gallardo-Alba C, Davis J, Föll MC, Fahrner M, Doyle MA, Serrano-Solano B, Fouilloux AC, van Heusden P, Maier W, Clements D, Heyl F; Galaxy Training Network; Grüning B, Batut B. PLoS Comput Biol. 2023 Jan 9;19(1):e1010752. doi: 10.1371/journal.pcbi.1010752. PMID: 36622853; PMCID: PMC9829167.

2022

Catching the Wave: Detecting Strain-Specific SARS-CoV-2 Peptides in Clinical Samples Collected during Infection Waves from Diverse Geographical Locations. Mehta S, Carvalho VM, Rajczewski AT, Pible O, Grüning BA, Johnson JE, Wagner R, Armengaud J, Griffin TJ, Jagtap PD. Viruses. 2022 Oct 7;14(10):2205. doi: 10.3390/v14102205. PMID: 36298760; PMCID: PMC9609567.

MaxQuant and MSstats in Galaxy Enable Reproducible Cloud-Based Analysis of Quantitative Proteomics Experiments for Everyone. Pinter N, Glätzer D, Fahrner M, Fröhlich K, Johnson J, Grüning BA, Warscheid B, Drepper F, Schilling O, Föll MC. J Proteome Res. 2022 Jun 3;21(6):1558-1565. doi: 10.1021/acs.jproteome.2c00051. Epub 2022 May 3. PMID: 35503992.

Gut microbial β-glucuronidases regulate host luminal proteases and are depleted in irritable bowel syndrome. Edwinson AL, Yang L, Peters S, Hanning N, Jeraldo P, Jagtap P, Simpson JB, Yang TY, Kumar P, Mehta S, Nair A, Breen-Lyles M, Chikkamenahalli L, Graham RP, De Winter B, Patel R, Dasari S, Kashyap P, Griffin T, Chen J, Farrugia G, Redinbo MR, Grover M. Nat Microbiol. 2022 May;7(5):680-694. doi: 10.1038/s41564-022-01103-1. Epub 2022 Apr 28. PMID: 35484230; PMCID: PMC9081267.

An overview of technologies for MS-based proteomics-centric multi-omics. Rajczewski AT, Jagtap PD, Griffin TJ. Expert Rev Proteomics. 2022 Mar;19(3):165-181. doi: 10.1080/14789450.2022.2070476. Epub 2022 May 2. PMID: 35466851; PMCID: PMC9613604.

Quantitative Proteogenomic Characterization of Inflamed Murine Colon Tissue Using an Integrated Discovery, Verification, and Validation Proteogenomic Workflow. Rajczewski AT, Han Q, Mehta S, Kumar P, Jagtap PD, Knutson CG, Fox JG, Tretyakova NY, Griffin TJ. Proteomes. 2022 Apr 14;10(2):11. doi: 10.3390/proteomes10020011. PMID: 35466239; PMCID: PMC9036229.

The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2022 update. Galaxy Community. Nucleic Acids Res. 2022 Jul 5;50(W1):W345-W351. doi: 10.1093/nar/gkac247. Erratum in: Nucleic Acids Res. 2022 Aug 26;50(15):8999. PMID: 35446428; PMCID: PMC9252830.

2021

The Metaproteomics Initiative: a coordinated approach for propelling the functional characterization of microbiomes. Van Den Bossche T, Arntzen MØ, Becher D, Benndorf D, Eijsink VGH, Henry C, Jagtap PD, Jehmlich N, Juste C, Kunath BJ, Mesuere B, Muth T, Pope PB, Seifert J, Tanca A, Uzzau S, Wilmes P, Hettich RL, Armengaud J. Microbiome. 2021 Dec 20;9(1):243. doi: 10.1186/s40168-021-01176-w. PMID: 34930457; PMCID: PMC8690404.

Critical Assessment of MetaProteome Investigation (CAMPI): a multi-laboratory comparison of established workflows. Van Den Bossche T, Kunath BJ, Schallert K, Schäpe SS, Abraham PE, Armengaud J, Arntzen MØ, Bassignani A, Benndorf D, Fuchs S, Giannone RJ, Griffin TJ, Hagen LH, Halder R, Henry C, Hettich RL, Heyer R, Jagtap P, Jehmlich N, Jensen M, Juste C, Kleiner M, Langella O, Lehmann T, Leith E, May P, Mesuere B, Miotello G, Peters SL, Pible O, Queiros PT, Reichl U, Renard BY, Schiebenhoefer H, Sczyrba A, Tanca A, Trappe K, Trezzi JP, Uzzau S, Verschaffelt P, von Bergen M, Wilmes P, Wolf M, Martens L, Muth T. Nat Commun. 2021 Dec 15;12(1):7305. doi: 10.1038/s41467-021-27542-8. PMID: 34911965; PMCID: PMC8674281.

Perspectives on automated composition of workflows in the life sciences. Lamprecht AL, Palmblad M, Ison J, Schwämmle V, Al Manir MS, Altintas I, Baker CJO, Ben Hadj Amor A, Capella-Gutierrez S, Charonyktakis P, Crusoe MR, Gil Y, Goble C, Griffin TJ, Groth P, Ienasescu H, Jagtap P, Kalaš M, Kasalica V, Khanteymoori A, Kuhn T, Mei H, Ménager H, Möller S, Richardson RA, Robert V, Soiland-Reyes S, Stevens R, Szaniszlo S, Verberne S, Verhoeven A, Wolstencroft K. F1000Res. 2021 Sep 7;10:897. doi: 10.12688/f1000research.54159.1. PMID: 34804501; PMCID: PMC8573700.

ASaiM-MT: a validated and optimized ASaiM workflow for metatranscriptomics analysis within Galaxy framework. Mehta S, Crane M, Leith E, Batut B, Hiltemann S, Arntzen MØ, Kunath BJ, Pope PB, Delogu F, Sajulga R, Kumar P, Johnson JE, Griffin TJ, Jagtap PD. F1000Res. 2021 Feb 11;10:103. doi: 10.12688/f1000research.28608.2. PMID: 34484688; PMCID: PMC8383124.

A rigorous evaluation of optimal peptide targets for MS-based clinical diagnostics of Coronavirus Disease 2019 (COVID-19). Rajczewski AT, Mehta S, Nguyen DDA, Grüning B, Johnson JE, McGowan T, Griffin TJ, Jagtap PD. Clin Proteomics. 2021 May 10;18(1):15. doi: 10.1186/s12014-021-09321-1. PMID: 33971807; PMCID: PMC8107781.

Updates on metaQuantome Software for Quantitative Metaproteomics. Mehta S, Kumar P, Crane M, Johnson JE, Sajulga R, Nguyen DDA, McGowan T, Arntzen MØ, Griffin TJ, Jagtap PD. J Proteome Res. 2021 Apr 2;20(4):2130-2137. doi: 10.1021/acs.jproteome.0c00960. Epub 2021 Mar 8. PMID: 33683127.

Metaproteomics Analysis of SARS-CoV-2-Infected Patient Samples Reveals Presence of Potential Coinfecting Microorganisms. Thuy-Boun PS, Mehta S, Gruening B, McGowan T, Nguyen A, Rajczewski AT, Johnson JE, Griffin TJ, Wolan DW, Jagtap PD.J Proteome Res. 2021 Feb 5;20(2):1451-1454. doi: 10.1021/acs.jproteome.0c00822. Epub 2021 Jan 4. PMID: 33393790; PMCID: PMC7805602.

2020

Survey of metaproteomics software tools for functional microbiome analysis. Sajulga R, Easterly C, Riffle M, Mesuere B, Muth T, Mehta S, Kumar P, Johnson J, Gruening BA, Schiebenhoefer H, Kolmeder CA, Fuchs S, Nunn BL, Rudney J, Griffin TJ, Jagtap PD. PLoS One. 2020 Nov 10;15(11):e0241503. doi: 10.1371/journal.pone.0241503. PMID: 33170893; PMCID: PMC7654790.

Novel protein pathways in development and progression of pulmonary sarcoidosis. Bhargava M, Viken KJ, Barkes B, Griffin TJ, Gillespie M, Jagtap PD, Sajulga R, Peterson EJ, Dincer HE, Li L, Restrepo CI, O’Connor BP, Fingerlin TE, Perlman DM, Maier LA. Sci Rep. 2020 Aug 6;10(1):13282. doi: 10.1038/s41598-020-69281-8. PMID: 32764642; PMCID: PMC7413390.

Precursor Intensity-Based Label-Free Quantification Software Tools for Proteomic and Multi-Omic Analysis within the Galaxy Platform. Mehta S, Easterly CW, Sajulga R, Millikin RJ, Argentini A, Eguinoa I, Martens L, Shortreed MR, Smith LM, McGowan T, Kumar P, Johnson JE, Griffin TJ, Jagtap PD. Proteomes. 2020 Jul 8;8(3):15. doi: 10.3390/proteomes8030015. PMID: 32650610; PMCID: PMC7563855.

A Sectioning and Database Enrichment Approach for Improved Peptide Spectrum Matching in Large, Genome-Guided Protein Sequence Databases. Kumar P, Johnson JE, Easterly C, Mehta S, Sajulga R, Nunn B, Jagtap PD, Griffin TJ. J Proteome Res. 2020 Jul 2;19(7):2772-2785. doi: 10.1021/acs.jproteome.0c00260. Epub 2020 May 26. PMID: 32396365.

Multi-omics Visualization Platform: An extensible Galaxy plug-in for multi-omics data visualization and exploration. McGowan T, Johnson JE, Kumar P, Sajulga R, Mehta S, Jagtap PD, Griffin TJ. Gigascience. 2020 Apr 1;9(4):giaa025. doi: 10.1093/gigascience/giaa025. PMID: 32236523; PMCID: PMC7102281.

The Cancer Microbiome: Distinguishing Direct and Indirect Effects Requires a Systemic View. Xavier JB, Young VB, Skufca J, Ginty F, Testerman T, Pearson AT, Macklin P, Mitchell A, Shmulevich I, Xie L, Caporaso JG, Crandall KA, Simone NL, Godoy-Vitorino F, Griffin TJ, Whiteson KL, Gustafson HH, Slade DJ, Schmidt TM, Walther-Antonio MRS, Korem T, Webb-Robertson BM, Styczynski MP, Johnson WE, Jobin C, Ridlon JM, Koh AY, Yu M, Kelly L, Wargo JA. Trends Cancer. 2020 Mar;6(3):192-204. doi: 10.1016/j.trecan.2020.01.004. Epub 2020 Feb 7. PMID: 32101723; PMCID: PMC7098063.

2019

Challenges in Peptide-Spectrum Matching: A Robust and Reproducible Statistical Framework for Removing Low-Accuracy, High-Scoring Hits. Hubler SL, Kumar P, Mehta S, Easterly C, Johnson JE, Jagtap PD, Griffin TJ. J Proteome Res. 2020 Jan 3;19(1):161-173. doi: 10.1021/acs.jproteome.9b00478. Epub 2019 Dec 20. PMID: 31793300.

metaQuantome: An Integrated, Quantitative Metaproteomics Approach Reveals Connections Between Taxonomy and Protein Function in Complex Microbiomes. Easterly CW, Sajulga R, Mehta S, Johnson J, Kumar P, Hubler S, Mesuere B, Rudney J, Griffin TJ, Jagtap PD. Mol Cell Proteomics. 2019 Aug 9;18(8 suppl 1):S82-S91. doi: 10.1074/mcp.RA118.001240. Epub 2019 Jun 24. PMID: 31235611; PMCID: PMC6692774.

The Galaxy Platform for Reproducible Affinity Proteomic Mass Spectrometry Data Analysis. Stewart PA, Kuenzi BM, Mehta S, Kumar P, Johnson JE, Jagtap P, Griffin TJ, Haura EB. Methods Mol Biol. 2019;1977:249-261. doi: 10.1007/978-1-4939-9232-4_16. PMID: 30980333; PMCID: PMC7787333.

Progress and Challenges in Ocean Metaproteomics and Proposed Best Practices for Data Sharing. Saito MA, Bertrand EM, Duffy ME, Gaylord DA, Held NA, Hervey WJ 4th, Hettich RL, Jagtap PD, Janech MG, Kinkade DB, Leary DH, McIlvin MR, Moore EK, Morris RM, Neely BA, Nunn BL, Saunders JK, Shepherd AI, Symmonds NI, Walsh DA. J Proteome Res. 2019 Apr 5;18(4):1461-1476. doi: 10.1021/acs.jproteome.8b00761. Epub 2019 Mar 12. PMID: 30702898; PMCID: PMC7575043.

Improve your Galaxy text life: The Query Tabular Tool. Johnson JE, Kumar P, Easterly C, Esler M, Mehta S, Eschenlauer AC, Hegeman AD, Jagtap PD, Griffin TJ. F1000Res. 2018 Oct 5;7:1604. doi: 10.12688/f1000research.16450.2. PMID: 30519459; PMCID: PMC6248266.

QuanTP: A Software Resource for Quantitative Proteo-Transcriptomic Comparative Data Analysis and Informatics. Kumar P, Panigrahi P, Johnson J, Weber WJ, Mehta S, Sajulga R, Easterly C, Crooker BA, Heydarian M, Anamika K, Griffin TJ, Jagtap PD. J Proteome Res. 2019 Feb 1;18(2):782-790. doi: 10.1021/acs.jproteome.8b00727. Epub 2019 Jan 4. PMID: 30582332.

 Update on the moFF Algorithm for Label-Free Quantitative Proteomics. Argentini A, Staes A, Grüning B, Mehta S, Easterly C, Griffin TJ, Jagtap P, Impens F, Martens L.J Proteome Res. 2019 Feb 1;18(2):728-731. doi: 10.1021/acs.jproteome.8b00708. Epub 2018 Dec 14. PMID: 30511867.

2018

BAL Fluid Metaproteome in Acute Respiratory Failure. Jagtap PD, Viken KJ, Johnson J, McGowan T, Pendleton KM, Griffin TJ, Hunter RC, Rudney JD, Bhargava M. Am J Respir Cell Mol Biol. 2018 Nov;59(5):648-652. doi: 10.1165/rcmb.2018-0068LE. PMID: 30382775; PMCID: PMC6236685.

Bridging the Chromosome-centric and Biology/Disease-driven Human Proteome Projects: Accessible and Automated Tools for Interpreting the Biological and Pathological Impact of Protein Sequence Variants Detected via Proteogenomics. Sajulga R, Mehta S, Kumar P, Johnson JE, Guerrero CR, Ryan MC, Karchin R, Jagtap PD, Griffin TJ. J Proteome Res. 2018 Dec 7;17(12):4329-4336. doi: 10.1021/acs.jproteome.8b00404. Epub 2018 Sep 5. PMID: 30130115.

Evaluating the potential of residual Pap test fluid as a resource for the metaproteomic analysis of the cervical-vaginal microbiome. Afiuni-Zadeh S, Boylan KLM, Jagtap PD, Griffin TJ, Rudney JD, Peterson ML, Skubitz APN. Sci Rep. 2018 Jul 18;8(1):10868. doi: 10.1038/s41598-018-29092-4. PMID: 30022083; PMCID: PMC6052116.

 Community-Driven Data Analysis Training for Biology. Batut B, Hiltemann S, Bagnacani A, Baker D, Bhardwaj V, Blank C, Bretaudeau A, Brillet-Guéguen L, Čech M, Chilton J, Clements D, Doppelt-Azeroual O, Erxleben A, Freeberg MA, Gladman S, Hoogstrate Y, Hotz HR, Houwaart T, Jagtap P, Larivière D, Le Corguillé G, Manke T, Mareuil F, Ramírez F, Ryan D, Sigloch FC, Soranzo N, Wolff J, Videm P, Wolfien M, Wubuli A, Yusuf D; Galaxy Training Network; Taylor J, Backofen R, Nekrutenko A, Grüning B.Cell Syst. 2018 Jun 27;6(6):752-758.e1. doi: 10.1016/j.cels.2018.05.012. PMID: 29953864; PMCID: PMC6296361.

Multi-omic molecular profiling of lung cancer in COPD. Sandri BJ, Kaplan A, Hodgson SW, Peterson M, Avdulov S, Higgins L, Markowski T, Yang P, Limper AH, Griffin TJ, Bitterman P, Lock EF, Wendt CH. Eur Respir J. 2018 Jul 4;52(1):1702665. doi: 10.1183/13993003.02665-2017. PMID: 29794131; PMCID: PMC6618293.

Disseminating Metaproteomic Informatics Capabilities and Knowledge Using the Galaxy-P Framework. Blank C, Easterly C, Gruening B, Johnson J, Kolmeder CA, Kumar P, May D, Mehta S, Mesuere B, Brown Z, Elias JE, Hervey WJ, McGowan T, Muth T, Nunn B, Rudney J, Tanca A, Griffin TJ, Jagtap PD. Proteomes. 2018 Jan 31;6(1):7. doi: 10.3390/proteomes6010007. PMID: 29385081; PMCID: PMC5874766.

2017

 An Accessible Proteogenomics Informatics Resource for Cancer Researchers. Chambers MC, Jagtap PD, Johnson JE, McGowan T, Kumar P, Onsongo G, Guerrero CR, Barsnes H, Vaudel M, Martens L, Grüning B, Cooke IR, Heydarian M, Reddy KL, Griffin TJ.Cancer Res. 2017 Nov 1;77(21):e43-e46. doi: 10.1158/0008-5472.CAN-17-0331. PMID: 29092937; PMCID: PMC5675041.

Bronchoalveolar Lavage Fluid Protein Expression in Acute Respiratory Distress Syndrome Provides Insights into Pathways Activated in Subjects with Different Outcomes. Bhargava M, Viken K, Wang Q, Jagtap P, Bitterman P, Ingbar D, Wendt C. Sci Rep. 2017 Aug 7;7(1):7464. doi: 10.1038/s41598-017-07791-8. PMID: 28785034; PMCID: PMC5547130.

2016

Seasonal changes in brown adipose tissue mitochondria in a mammalian hibernator: from gene expression to function. Ballinger MA, Hess C, Napolitano MW, Bjork JA, Andrews MT. Am J Physiol Regul Integr Comp Physiol. 2016 Aug 1;311(2):R325-36. doi: 10.1152/ajpregu.00463.2015. Epub 2016 May 25. PMID: 27225952.

Proteome Profiling in Lung Injury after Hematopoietic Stem Cell Transplantation. Bhargava M, Viken KJ, Dey S, Steinbach MS, Wu B, Jagtap PD, Higgins L, Panoskaltsis-Mortari A, Weisdorf DJ, Kumar V, Arora M, Bitterman PB, Ingbar DH, Wendt CH. Biol Blood Marrow Transplant. 2016 Aug;22(8):1383-1390. doi: 10.1016/j.bbmt.2016.04.021. Epub 2016 May 5. PMID: 27155584; PMCID: PMC4955710.

Decreased Laminin Expression by Human Lung Epithelial Cells and Fibroblasts Cultured in Acellular Lung Scaffolds from Aged Mice. Godin LM, Sandri BJ, Wagner DE, Meyer CM, Price AP, Akinnola I, Weiss DJ, Panoskaltsis-Mortari A. PLoS One. 2016 Mar 8;11(3):e0150966. doi: 10.1371/journal.pone.0150966. PMID: 26954258; PMCID: PMC4783067.

Proteome Profiling in Lung Injury after Hematopoietic Stem Cell Transplantation. Bhargava M, Viken KJ, Dey S, Steinbach MS, Wu B, Jagtap PD, Higgins L, Panoskaltsis-Mortari A, Weisdorf DJ, Kumar V, Arora M, Bitterman PB, Ingbar DH, Wendt CH. Biol Blood Marrow Transplant. 2016 Aug;22(8):1383-1390. doi: 10.1016/j.bbmt.2016.04.021. Epub 2016 May 5. PMID: 27155584; PMCID: PMC4955710.

Proteome Scale-Protein Turnover Analysis Using High Resolution Mass Spectrometric Data from Stable-Isotope Labeled Plants. Fan KT, Rendahl AK, Chen WP, Freund DM, Gray WM, Cohen JD, Hegeman AD. J Proteome Res. 2016 Mar 4;15(3):851-67. doi: 10.1021/acs.jproteome.5b00772. Epub 2016 Jan 29. PMID: 26824330; PMCID: PMC5482238.

Human Proteomic Variation Revealed by Combining RNA-Seq Proteogenomics and Global Post-Translational Modification (G-PTM) Search Strategy. Cesnik AJ, Shortreed MR, Sheynkman GM, Frey BL, Smith LM. J Proteome Res. 2016 Mar 4;15(3):800-8. doi: 10.1021/acs.jproteome.5b00817. Epub 2016 Jan 12. PMID: 26704769; PMCID: PMC4779408.

2015

Protein relative abundance patterns associated with sucrose-induced dysbiosis are conserved across taxonomically diverse oral microcosm biofilm models of dental caries. Rudney JD, Jagtap PD, Reilly CS, Chen R, Markowski TW, Higgins L, Johnson JE, Griffin TJ. Microbiome. 2015 Dec 19;3:69. doi: 10.1186/s40168-015-0136-z. PMID: 26684897; PMCID: PMC4684605.

Characterizing Cardiac Molecular Mechanisms of Mammalian Hibernation via Quantitative Proteogenomics. Vermillion KL, Jagtap P, Johnson JE, Griffin TJ, Andrews MT. J Proteome Res. 2015 Nov 6;14(11):4792-804. doi: 10.1021/acs.jproteome.5b00575. Epub 2015 Oct 23. PMID: 26435507.

Metaproteomic analysis using the Galaxy framework. Jagtap PD, Blakely A, Murray K, Stewart S, Kooren J, Johnson JE, Rhodus NL, Rudney J, Griffin TJ.  Proteomics.2015 Oct;15(20):3553-65. doi: 10.1002/pmic.201500074. Epub 2015 Jul 24. PMID: 26058579.

Multi-omic data analysis using Galaxy. Boekel J, Chilton JM, Cooke IR, Horvatovich PL, Jagtap PD, Käll L, Lehtiö J, Lukasse P, Moerland PD, Griffin TJ. Nat Biotechnol.2015 Feb;33(2):137-9. doi: 10.1038/nbt.3134. PMID: 25658277.

2014

Flexible and accessible workflows for improved proteogenomic analysis using the Galaxy framework. Jagtap PD, Johnson JE, Onsongo G, Sadler FW, Murray K, Wang Y, Shenykman GM, Bandhakavi S, Smith LM, Griffin TJ. J Proteome Res. 2014 Dec 5;13(12):5898-908. doi: 10.1021/pr500812t. Epub 2014 Oct 23. PMID: 25301683; PMCID: PMC4261978.

Proteomic profiles in acute respiratory distress syndrome differentiates survivors from non-survivors. Bhargava M, Becker TL, Viken KJ, Jagtap PD, Dey S, Steinbach MS, Wu B, Kumar V, Bitterman PB, Ingbar DH, Wendt CH. PLoS One. 2014 Oct 7;9(10):e109713. doi: 10.1371/journal.pone.0109713. PMID: 25290099; PMCID: PMC4188744.

Using Galaxy-P to leverage RNA-Seq for the discovery of novel protein variations. Sheynkman GM, Johnson JE, Jagtap PD, Shortreed MR, Onsongo G, Frey BL, Griffin TJ, Smith LM. BMC Genomics. 2014 Aug 22;15(1):703. doi: 10.1186/1471-2164-15-703. PMID: 25149441; PMCID: PMC4158061.