Difference between revisions of "Journal:CytoConverter: A web-based tool to convert karyotypes to genomic coordinates"
Shawndouglas (talk | contribs) (Created stub. Saving and adding more.) |
Shawndouglas (talk | contribs) |
||
| Line 37: | Line 37: | ||
==Background== | ==Background== | ||
Many human diseases, particularly [[cancer]], are caused by or driven by gains and losses of chromosomes or chromosomal segments.<ref name="BeroukhimTheLand10">{{cite journal |title=The landscape of somatic copy-number alteration across human cancers |journal=Nature |author=Beroukhim, R.; Mermel, C.H.; Porter, D. et al. |volume=463 |issue=7283 |pages=899–905 |year=2010 |doi=10.1038/nature08822 |pmid=20164920 |pmc=PMC2826709}}</ref> In cancer, oncogenes are often found within regions of gain, while tumor suppressor genes are frequently deleted.<ref name="SmithSystem18">{{cite journal |title=Systematic identification of mutations and copy number alterations associated with cancer patient prognosis |journal=eLife |author=Smith, J.C.; Sheltzer, J.M. |volume=7 |page=e39217 |year=2018 |doi=10.7554/eLife.39217 |pmid=30526857 |pmc=PMC6289580}}</ref> Chromosomal abnormalities also cause many known syndromes, and may be suspected as causes of undiagnosed diseases.<ref name="TheisenDisord10">{{cite journal |title=Disorders caused by chromosome abnormalities |journal=The Application of Clinical Genetics |author=Theisen, A.; Shaffer, L.G. |volume=3 |pages=159–74 |year=2010 |doi=10.2147/TACG.S8884 |pmid=23776360 |pmc=PMC3681172}}</ref> As such, testing for gains and losses is an important component of both research and clinical practice. | Many human diseases, particularly [[cancer]], are caused by or driven by gains and losses of chromosomes or chromosomal segments.<ref name="BeroukhimTheLand10">{{cite journal |title=The landscape of somatic copy-number alteration across human cancers |journal=Nature |author=Beroukhim, R.; Mermel, C.H.; Porter, D. et al. |volume=463 |issue=7283 |pages=899–905 |year=2010 |doi=10.1038/nature08822 |pmid=20164920 |pmc=PMC2826709}}</ref> In cancer, oncogenes are often found within regions of gain, while tumor suppressor genes are frequently deleted.<ref name="SmithSystem18">{{cite journal |title=Systematic identification of mutations and copy number alterations associated with cancer patient prognosis |journal=eLife |author=Smith, J.C.; Sheltzer, J.M. |volume=7 |page=e39217 |year=2018 |doi=10.7554/eLife.39217 |pmid=30526857 |pmc=PMC6289580}}</ref> Chromosomal abnormalities also cause many known syndromes, and may be suspected as causes of undiagnosed diseases.<ref name="TheisenDisord10">{{cite journal |title=Disorders caused by chromosome abnormalities |journal=The Application of Clinical Genetics |author=Theisen, A.; Shaffer, L.G. |volume=3 |pages=159–74 |year=2010 |doi=10.2147/TACG.S8884 |pmid=23776360 |pmc=PMC3681172}}</ref> As such, testing for gains and losses is an important component of both research and clinical practice. | ||
Before the advent of higher-resolution techniques, karyotypes were the primary method used to characterize chromosomal aberrations, and they are still widely used. A karyotype summarizes the state of the genetic material in a collection of cells. The naming system for describing chromosomal changes—cytogenetic nomenclature—is dictated by the International System for Human Cytogenomic Nomenclature (ISCN).<ref name="McGowan-JordanISCN16">{{cite book |title=ISCN 2016: An International System for Human Cytogenomic Nomenclature (2016) |editor=McGowan-Jordan, J.; Simons, A.; Schmid, W. |publisher=Karger International |year=2016 |isbn=9783318058574}}</ref> It describes the total number of chromosomes in the cell, the unmodified sex chromosomes, and the chromosome(s) with abnormalities present. Karyotyping relies on the use of banding techniques, which have allowed researchers to describe the locations of microscopic-level changes such as translocations and band-sized or larger deletions and duplications. The completion of the human genome sequence in the early 2000s, however, enabled description of chromosomal aberrations in terms of genomic coordinates, which can specify locations at nucleotide-level resolution.<ref name="NaidooHuman11">{{cite journal |title=Human genetics and genomics a decade after the release of the draft sequence of the human genome |journal=Human Genomics |author=Naidoo, N.; Pawitan, T.; Soong, R. et al. |volume=5 |issue=6 |pages=577-622 |year=2011 |doi=10.1186/1479-7364-5-6-577 |pmid=22155605 |pmc=PMC3525251}}</ref> Technological advances such as genotyping microarrays (reviewed by LaFramboise in 2009<ref name="LaFramboiseSingle09">{{cite journal |title=Single nucleotide polymorphism arrays: A decade of biological, computational and technological advances |journal=Nucleic Acids Research |author=LaFramboise, T. |volume=37 |issue=13 |pages=4181–93 |year=2009 |doi=10.1093/nar/gkp552 |pmid=19570852 |pmc=PMC2715261}}</ref>) and, more recently, [[DNA sequencing#High-throughput methods|next-generation sequencing]] (NGS) have spurred the community to more commonly frame deletions and gains in terms of genomic coordinates. However, karyotyping is still used today.<ref name="LiDistinct16">{{cite journal |title=Distinct evolution and dynamics of epigenetic and genetic heterogeneity in acute myeloid leukemia |journal=Nature Medicine |author=Li, S.; Garrett-Bakelman, F.E.; Chung, S.S. et al. |volume=22 |issue=7 |pages=792–9 |year=2016 |doi=10.1038/nm.4125 |pmid=27322744 |pmc=PMC4938719}}</ref> The use of cytogenetics remains popular for analyzing blood samples<ref name="Ferguson-SmithHist15">{{cite journal |title=History and evolution of cytogenetics |journal=Molecular Cytogenetics |author=Ferguson-Smith, M.A. |volume=8 |pages=19 |year=2015 |doi=10.1186/s13039-015-0125-8 |pmid=25810762 |pmc=PMC4373004}}</ref>, for example. Additionally, there is copious archival data (e.g., the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer) recorded in cytogenetic nomenclature. Large numbers of these karyotyped samples have not been subjected to microarray or NGS-based analyses, and in many cases the DNA is no longer available. In order to allow researchers to more easily identify the genomic entities such as genes and regulatory loci that are harbored in the gained and lost regions of karyotyped samples, we have developed a converter that parses the karyotypes and returns the corresponding gains and losses in terms of genomic coordinates. | |||
Revision as of 22:05, 16 December 2019
| Full article title | CytoConverter: A web-based tool to convert karyotypes to genomic coordinates |
|---|---|
| Journal | BMC Bioinformatics |
| Author(s) | Wang, Janet; LaFramboise, Thomas |
| Author affiliation(s) | Case Western Reserve University |
| Primary contact | Email: Thomas dot LaFramboise at case dot edu |
| Year published | 2019 |
| Volume and issue | 20 |
| Page(s) | 467 |
| DOI | [ https://doi.org/10.1186/s12859-019-3062-4 10.1186/s12859-019-3062-4] |
| ISSN | 1471-2105 |
| Distribution license | Creative Commons Attribution 4.0 International |
| Website | https://link.springer.com/article/10.1186/s12859-019-3062-4 |
| Download | https://link.springer.com/content/pdf/10.1186%2Fs12859-019-3062-4.pdf (PDF) |
 |
This article should be considered a work in progress and incomplete. Consider this article incomplete until this notice is removed. |
Abstract
Background: Cytogenetic nomenclature is used to describe chromosomal aberrations (or lack thereof) in a collection of cells, referred to as the cells’ karyotype. The nomenclature identifies locations on chromosomes using a system of cytogenetic bands, each with a unique name and region on a chromosome. Each band is microscopically visible after staining, and it encompasses a large portion of the chromosome. More modern analyses employ genomic coordinates, which precisely specify a chromosomal location according to its distance from the end of the chromosome. Currently, there is no tool to convert cytogenetic nomenclature into genomic coordinates. Since locations of genes and other genomic features are usually specified by genomic coordinates, a conversion tool will facilitate the identification of the features that are harbored in the regions of chromosomal gain and loss that are implied by a karyotype.
Results: Our tool, termed CytoConverter, takes as input either a single karyotype or a file consisting of multiple karyotypes from several individuals. All net chromosomal gains and losses implied by the karyotype are returned in standard genomic coordinates, along with the numbers of cells harboring each aberration if included in the input. CytoConverter also returns graphical output detailing areas of gains and losses of chromosomes and chromosomal segments.
Conclusions: CytoConverter is available as a web-based application and as an R script. Supplemental Material detailing the underlying algorithms is available.
Keywords: cytogenetics, chromosomal abnormalities, karyotypes, text parsing
Background
Many human diseases, particularly cancer, are caused by or driven by gains and losses of chromosomes or chromosomal segments.[1] In cancer, oncogenes are often found within regions of gain, while tumor suppressor genes are frequently deleted.[2] Chromosomal abnormalities also cause many known syndromes, and may be suspected as causes of undiagnosed diseases.[3] As such, testing for gains and losses is an important component of both research and clinical practice.
Before the advent of higher-resolution techniques, karyotypes were the primary method used to characterize chromosomal aberrations, and they are still widely used. A karyotype summarizes the state of the genetic material in a collection of cells. The naming system for describing chromosomal changes—cytogenetic nomenclature—is dictated by the International System for Human Cytogenomic Nomenclature (ISCN).[4] It describes the total number of chromosomes in the cell, the unmodified sex chromosomes, and the chromosome(s) with abnormalities present. Karyotyping relies on the use of banding techniques, which have allowed researchers to describe the locations of microscopic-level changes such as translocations and band-sized or larger deletions and duplications. The completion of the human genome sequence in the early 2000s, however, enabled description of chromosomal aberrations in terms of genomic coordinates, which can specify locations at nucleotide-level resolution.[5] Technological advances such as genotyping microarrays (reviewed by LaFramboise in 2009[6]) and, more recently, next-generation sequencing (NGS) have spurred the community to more commonly frame deletions and gains in terms of genomic coordinates. However, karyotyping is still used today.[7] The use of cytogenetics remains popular for analyzing blood samples[8], for example. Additionally, there is copious archival data (e.g., the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer) recorded in cytogenetic nomenclature. Large numbers of these karyotyped samples have not been subjected to microarray or NGS-based analyses, and in many cases the DNA is no longer available. In order to allow researchers to more easily identify the genomic entities such as genes and regulatory loci that are harbored in the gained and lost regions of karyotyped samples, we have developed a converter that parses the karyotypes and returns the corresponding gains and losses in terms of genomic coordinates.
Abbreviations
AML: Acute myeloid leukemia
ISCN: International System for Human Cytogenomic Nomenclature
NCBI: National Center for Biotechnology Information
NGS: Next-generation sequencing
References
- ↑ Beroukhim, R.; Mermel, C.H.; Porter, D. et al. (2010). "The landscape of somatic copy-number alteration across human cancers". Nature 463 (7283): 899–905. doi:10.1038/nature08822. PMC PMC2826709. PMID 20164920. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826709.
- ↑ Smith, J.C.; Sheltzer, J.M. (2018). "Systematic identification of mutations and copy number alterations associated with cancer patient prognosis". eLife 7: e39217. doi:10.7554/eLife.39217. PMC PMC6289580. PMID 30526857. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289580.
- ↑ Theisen, A.; Shaffer, L.G. (2010). "Disorders caused by chromosome abnormalities". The Application of Clinical Genetics 3: 159–74. doi:10.2147/TACG.S8884. PMC PMC3681172. PMID 23776360. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681172.
- ↑ McGowan-Jordan, J.; Simons, A.; Schmid, W., ed. (2016). ISCN 2016: An International System for Human Cytogenomic Nomenclature (2016). Karger International. ISBN 9783318058574.
- ↑ Naidoo, N.; Pawitan, T.; Soong, R. et al. (2011). "Human genetics and genomics a decade after the release of the draft sequence of the human genome". Human Genomics 5 (6): 577-622. doi:10.1186/1479-7364-5-6-577. PMC PMC3525251. PMID 22155605. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3525251.
- ↑ LaFramboise, T. (2009). "Single nucleotide polymorphism arrays: A decade of biological, computational and technological advances". Nucleic Acids Research 37 (13): 4181–93. doi:10.1093/nar/gkp552. PMC PMC2715261. PMID 19570852. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715261.
- ↑ Li, S.; Garrett-Bakelman, F.E.; Chung, S.S. et al. (2016). "Distinct evolution and dynamics of epigenetic and genetic heterogeneity in acute myeloid leukemia". Nature Medicine 22 (7): 792–9. doi:10.1038/nm.4125. PMC PMC4938719. PMID 27322744. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938719.
- ↑ Ferguson-Smith, M.A. (2015). "History and evolution of cytogenetics". Molecular Cytogenetics 8: 19. doi:10.1186/s13039-015-0125-8. PMC PMC4373004. PMID 25810762. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373004.
Notes
This presentation is faithful to the original, with only a few minor changes to presentation, spelling, and grammar. We also added PMCID and DOI when they were missing from the original reference. The original article lists references alphabetically, but this version—by design—lists them in order of appearance.
