--- _id: '2250' abstract: - lang: eng text: The genome sequences of new viruses often contain many "orphan" or "taxon-specific" proteins apparently lacking homologs. However, because viral proteins evolve very fast, commonly used sequence similarity detection methods such as BLAST may overlook homologs. We analyzed a data set of proteins from RNA viruses characterized as "genus specific" by BLAST. More powerful methods developed recently, such as HHblits or HHpred (available through web-based, user-friendly interfaces), could detect distant homologs of a quarter of these proteins, suggesting that these methods should be used to annotate viral genomes. In-depth manual analyses of a subset of the remaining sequences, guided by contextual information such as taxonomy, gene order, or domain cooccurrence, identified distant homologs of another third. Thus, a combination of powerful automated methods and manual analyses can uncover distant homologs of many proteins thought to be orphans. We expect these methodological results to be also applicable to cellular organisms, since they generally evolve much more slowly than RNA viruses. As an application, we reanalyzed the genome of a bee pathogen, Chronic bee paralysis virus (CBPV). We could identify homologs of most of its proteins thought to be orphans; in each case, identifying homologs provided functional clues. We discovered that CBPV encodes a domain homologous to the Alphavirus methyltransferase-guanylyltransferase; a putative membrane protein, SP24, with homologs in unrelated insect viruses and insect-transmitted plant viruses having different morphologies (cileviruses, higreviruses, blunerviruses, negeviruses); and a putative virion glycoprotein, ORF2, also found in negeviruses. SP24 and ORF2 are probably major structural components of the virionsd. author: - first_name: Durga full_name: Kuchibhatla, Durga last_name: Kuchibhatla - first_name: Westley full_name: Sherman, Westley last_name: Sherman - first_name: Betty full_name: Chung, Betty last_name: Chung - first_name: Shelley full_name: Cook, Shelley last_name: Cook - first_name: Georg full_name: Schneider, Georg id: 329095A0-F248-11E8-B48F-1D18A9856A87 last_name: Schneider - first_name: Birgit full_name: Eisenhaber, Birgit last_name: Eisenhaber - first_name: David full_name: Karlin, David last_name: Karlin citation: ama: Kuchibhatla D, Sherman W, Chung B, et al. Powerful sequence similarity search methods and in-depth manual analyses can identify remote homologs in many apparently “orphan” viral proteins. Journal of Virology. 2014;88(1):10-20. doi:10.1128/JVI.02595-13 apa: Kuchibhatla, D., Sherman, W., Chung, B., Cook, S., Schneider, G., Eisenhaber, B., & Karlin, D. (2014). Powerful sequence similarity search methods and in-depth manual analyses can identify remote homologs in many apparently “orphan” viral proteins. Journal of Virology. ASM. https://doi.org/10.1128/JVI.02595-13 chicago: Kuchibhatla, Durga, Westley Sherman, Betty Chung, Shelley Cook, Georg Schneider, Birgit Eisenhaber, and David Karlin. “Powerful Sequence Similarity Search Methods and In-Depth Manual Analyses Can Identify Remote Homologs in Many Apparently ‘Orphan’ Viral Proteins.” Journal of Virology. ASM, 2014. https://doi.org/10.1128/JVI.02595-13. ieee: D. Kuchibhatla et al., “Powerful sequence similarity search methods and in-depth manual analyses can identify remote homologs in many apparently ‘orphan’ viral proteins,” Journal of Virology, vol. 88, no. 1. ASM, pp. 10–20, 2014. ista: Kuchibhatla D, Sherman W, Chung B, Cook S, Schneider G, Eisenhaber B, Karlin D. 2014. Powerful sequence similarity search methods and in-depth manual analyses can identify remote homologs in many apparently ‘orphan’ viral proteins. Journal of Virology. 88(1), 10–20. mla: Kuchibhatla, Durga, et al. “Powerful Sequence Similarity Search Methods and In-Depth Manual Analyses Can Identify Remote Homologs in Many Apparently ‘Orphan’ Viral Proteins.” Journal of Virology, vol. 88, no. 1, ASM, 2014, pp. 10–20, doi:10.1128/JVI.02595-13. short: D. Kuchibhatla, W. Sherman, B. Chung, S. Cook, G. Schneider, B. Eisenhaber, D. Karlin, Journal of Virology 88 (2014) 10–20. date_created: 2018-12-11T11:56:34Z date_published: 2014-01-01T00:00:00Z date_updated: 2021-01-12T06:56:17Z day: '01' ddc: - '570' department: - _id: MD doi: 10.1128/JVI.02595-13 file: - access_level: open_access checksum: 2c121b5e884992dfec5605bdf4e659da content_type: application/pdf creator: system date_created: 2018-12-12T10:13:43Z date_updated: 2020-07-14T12:45:34Z file_id: '5029' file_name: IST-2016-417-v1+1_J._Virol.-2014-Kuchibhatla-10-20.pdf file_size: 825756 relation: main_file file_date_updated: 2020-07-14T12:45:34Z has_accepted_license: '1' intvolume: ' 88' issue: '1' language: - iso: eng month: '01' oa: 1 oa_version: Published Version page: 10 - 20 publication: Journal of Virology publication_identifier: issn: - 0022538X publication_status: published publisher: ASM publist_id: '4698' pubrep_id: '417' quality_controlled: '1' scopus_import: 1 status: public title: Powerful sequence similarity search methods and in-depth manual analyses can identify remote homologs in many apparently "orphan" viral proteins tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 88 year: '2014' ... --- _id: '2826' abstract: - lang: eng text: Myopia, or near-sightedness, is an ocular refractive error of unfocused image quality in front of the retinal plane. Individuals with high-grade myopia (dioptric power greater than -6.00) are predisposed to ocular morbidities such as glaucoma, retinal detachment, and myopic maculopathy. Nonsyndromic, high-grade myopia is highly heritable, and to date multiple gene loci have been reported. We performed exome sequencing in 4 individuals from an 11-member family of European descent from the United States. Affected individuals had a mean dioptric spherical equivalent of -22.00 sphere. A premature stop codon mutation c.157C>T (p.Gln53*) cosegregating with disease was discovered within SCO2 that maps to chromosome 22q13.33. Subsequent analyses identified three additional mutations in three highly myopic unrelated individuals (c.341G>A, c.418G>A, and c.776C>T). To determine differential gene expression in a developmental mouse model, we induced myopia by applying a -15.00D lens over one eye. Messenger RNA levels of SCO2 were significantly downregulated in myopic mouse retinae. Immunohistochemistry in mouse eyes confirmed SCO2 protein localization in retina, retinal pigment epithelium, and sclera. SCO2 encodes for a copper homeostasis protein influential in mitochondrial cytochrome c oxidase activity. Copper deficiencies have been linked with photoreceptor loss and myopia with increased scleral wall elasticity. Retinal thinning has been reported with an SC02 variant. Human mutation identification with support from an induced myopic animal provides biological insights of myopic development. author: - first_name: Khanh full_name: Tran Viet, Khanh last_name: Tran Viet - first_name: Caldwell full_name: Powell, Caldwell last_name: Powell - first_name: Veluchamy full_name: Barathi, Veluchamy last_name: Barathi - first_name: Thomas full_name: Klemm, Thomas last_name: Klemm - first_name: Sebastian full_name: Maurer Stroh, Sebastian last_name: Maurer Stroh - first_name: Vachiranee full_name: Limviphuvadh, Vachiranee last_name: Limviphuvadh - first_name: Vincent full_name: Soler, Vincent last_name: Soler - first_name: Candice full_name: Ho, Candice last_name: Ho - first_name: Tammy full_name: Yanovitch, Tammy last_name: Yanovitch - first_name: Georg full_name: Schneider, Georg id: 329095A0-F248-11E8-B48F-1D18A9856A87 last_name: Schneider - first_name: Yi full_name: Li, Yi last_name: Li - first_name: Erica full_name: Nading, Erica last_name: Nading - first_name: Ravikanth full_name: Metlapally, Ravikanth last_name: Metlapally - first_name: Seang full_name: Saw, Seang last_name: Saw - first_name: Liang full_name: Goh, Liang last_name: Goh - first_name: Steve full_name: Rozen, Steve last_name: Rozen - first_name: Terri full_name: Young, Terri last_name: Young citation: ama: Tran Viet K, Powell C, Barathi V, et al. Mutations in SCO2 are associated with autosomal-dominant high-grade myopia. American Journal of Human Genetics. 2013;92(5):820-826. doi:10.1016/j.ajhg.2013.04.005 apa: Tran Viet, K., Powell, C., Barathi, V., Klemm, T., Maurer Stroh, S., Limviphuvadh, V., … Young, T. (2013). Mutations in SCO2 are associated with autosomal-dominant high-grade myopia. American Journal of Human Genetics. Cell Press. https://doi.org/10.1016/j.ajhg.2013.04.005 chicago: Tran Viet, Khanh, Caldwell Powell, Veluchamy Barathi, Thomas Klemm, Sebastian Maurer Stroh, Vachiranee Limviphuvadh, Vincent Soler, et al. “Mutations in SCO2 Are Associated with Autosomal-Dominant High-Grade Myopia.” American Journal of Human Genetics. Cell Press, 2013. https://doi.org/10.1016/j.ajhg.2013.04.005. ieee: K. Tran Viet et al., “Mutations in SCO2 are associated with autosomal-dominant high-grade myopia,” American Journal of Human Genetics, vol. 92, no. 5. Cell Press, pp. 820–826, 2013. ista: Tran Viet K, Powell C, Barathi V, Klemm T, Maurer Stroh S, Limviphuvadh V, Soler V, Ho C, Yanovitch T, Schneider G, Li Y, Nading E, Metlapally R, Saw S, Goh L, Rozen S, Young T. 2013. Mutations in SCO2 are associated with autosomal-dominant high-grade myopia. American Journal of Human Genetics. 92(5), 820–826. mla: Tran Viet, Khanh, et al. “Mutations in SCO2 Are Associated with Autosomal-Dominant High-Grade Myopia.” American Journal of Human Genetics, vol. 92, no. 5, Cell Press, 2013, pp. 820–26, doi:10.1016/j.ajhg.2013.04.005. short: K. Tran Viet, C. Powell, V. Barathi, T. Klemm, S. Maurer Stroh, V. Limviphuvadh, V. Soler, C. Ho, T. Yanovitch, G. Schneider, Y. Li, E. Nading, R. Metlapally, S. Saw, L. Goh, S. Rozen, T. Young, American Journal of Human Genetics 92 (2013) 820–826. date_created: 2018-12-11T11:59:48Z date_published: 2013-05-02T00:00:00Z date_updated: 2021-01-12T06:59:59Z day: '02' department: - _id: MD doi: 10.1016/j.ajhg.2013.04.005 external_id: pmid: - '23643385' intvolume: ' 92' issue: '5' language: - iso: eng main_file_link: - open_access: '1' url: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644634/ month: '05' oa: 1 oa_version: Submitted Version page: 820 - 826 pmid: 1 publication: American Journal of Human Genetics publication_status: published publisher: Cell Press publist_id: '3974' quality_controlled: '1' scopus_import: 1 status: public title: Mutations in SCO2 are associated with autosomal-dominant high-grade myopia type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 92 year: '2013' ...