---
_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
license: https://creativecommons.org/licenses/by/4.0/
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'
...