CINdex: A Bioconductor Package for Analysis of Chromosome Instability in DNA Copy Number Data

Overview

Journal Cancer Inform

Publisher Sage Publications

Specialty Biomedical Engineering

Date 2018 Jan 19

PMID 29343938

Citations 5

Authors

Lei Song

Krithika Bhuvaneshwar

Yue Wang

Yuanjian Feng

Ie-Ming Shih

Subha Madhavan

Yuriy Gusev

Affiliations

Soon will be listed here.

Abstract

The CINdex Bioconductor package addresses an important area of high-throughput genomic analysis. It calculates the chromosome instability (CIN) index, a novel measurement that quantitatively characterizes genome-wide copy number alterations (CNAs) as a measure of CIN. The advantage of this package is an ability to compare CIN index values between several groups for patients (case and control groups), which is a typical use case in translational research. The differentially changed cytobands or chromosomes can then be linked to genes located in the affected genomic regions, as well as pathways. This enables in-depth systems biology-based network analysis and assessment of the impact of CNA on various biological processes or clinical outcomes. This package was successfully applied to analysis of DNA copy number data in colorectal cancer as a part of multi-omics integrative study as well as for analysis of several other cancer types. The source code, along with an end-to-end tutorial, and example data are freely available in Bioconductor at http://bioconductor.org/packages/CINdex/.

Citing Articles

Chromosomal instability: a key driver in glioma pathogenesis and progression.

Mazzoleni A, Awuah W, Sanker V, Bharadwaj H, Aderinto N, Tan J Eur J Med Res. 2024; 29(1):451.

PMID: 39227895 PMC: 11373396. DOI: 10.1186/s40001-024-02043-8.

CINmetrics: an R package for analyzing copy number aberrations as a measure of chromosomal instability.

Oza V, Fisher J, Darji R, Lasseigne B PeerJ. 2023; 11:e15244.

PMID: 37123011 PMC: 10143595. DOI: 10.7717/peerj.15244.

The Long Noncoding RNA CCAT2 Induces Chromosomal Instability Through BOP1-AURKB Signaling.

Chen B, Dragomir M, Fabris L, Bayraktar R, Knutsen E, Liu X Gastroenterology. 2020; 159(6):2146-2162.e33.

PMID: 32805281 PMC: 7725986. DOI: 10.1053/j.gastro.2020.08.018.

Ontogenetic and Pathogenetic Views on Somatic Chromosomal Mosaicism.

Iourov I, Vorsanova S, Yurov Y, Kutsev S Genes (Basel). 2019; 10(5).

PMID: 31109140 PMC: 6562967. DOI: 10.3390/genes10050379.

The REMBRANDT study, a large collection of genomic data from brain cancer patients.

Gusev Y, Bhuvaneshwar K, Song L, Zenklusen J, Fine H, Madhavan S Sci Data. 2018; 5:180158.

PMID: 30106394 PMC: 6091243. DOI: 10.1038/sdata.2018.158.

References

van Wezel T, Lombaerts M, van Roon E, Philippo K, Baelde H, Szuhai K . Expression analysis of candidate breast tumour suppressor genes on chromosome 16q. Breast Cancer Res. 2005; 7(6):R998-1004. PMC: 1410740. DOI: 10.1186/bcr1337. View

Lawrence M, Huber W, Pages H, Aboyoun P, Carlson M, Gentleman R . Software for computing and annotating genomic ranges. PLoS Comput Biol. 2013; 9(8):e1003118. PMC: 3738458. DOI: 10.1371/journal.pcbi.1003118. View

Hupe P, Stransky N, Thiery J, Radvanyi F, Barillot E . Analysis of array CGH data: from signal ratio to gain and loss of DNA regions. Bioinformatics. 2004; 20(18):3413-22. DOI: 10.1093/bioinformatics/bth418. View

Alkebsi L, Handa H, Yokohama A, Saitoh T, Tsukamoto N, Murakami H . Chromosome 16q genes and are correlated and frequently methylated in human lymphoma. Oncol Lett. 2016; 12(5):3523-3530. PMC: 5103978. DOI: 10.3892/ol.2016.5116. View

Crespo I, Vital A, Nieto A, Rebelo O, Tao H, Lopes M . Detailed characterization of alterations of chromosomes 7, 9, and 10 in glioblastomas as assessed by single-nucleotide polymorphism arrays. J Mol Diagn. 2011; 13(6):634-47. PMC: 3194060. DOI: 10.1016/j.jmoldx.2011.06.003. View

Pino M, Chung D . The chromosomal instability pathway in colon cancer. Gastroenterology. 2010; 138(6):2059-72. PMC: 4243705. DOI: 10.1053/j.gastro.2009.12.065. View

Madhavan S, Gusev Y, Natarajan T, Song L, Bhuvaneshwar K, Gauba R . Genome-wide multi-omics profiling of colorectal cancer identifies immune determinants strongly associated with relapse. Front Genet. 2013; 4:236. PMC: 3834519. DOI: 10.3389/fgene.2013.00236. View

Madhavan S, Gusev Y, Harris M, Tanenbaum D, Gauba R, Bhuvaneshwar K . G-DOC: a systems medicine platform for personalized oncology. Neoplasia. 2011; 13(9):771-83. PMC: 3182270. DOI: 10.1593/neo.11806. View

Kuo K, Guan B, Feng Y, Mao T, Chen X, Jinawath N . Analysis of DNA copy number alterations in ovarian serous tumors identifies new molecular genetic changes in low-grade and high-grade carcinomas. Cancer Res. 2009; 69(9):4036-42. PMC: 2782554. DOI: 10.1158/0008-5472.CAN-08-3913. View

10.

Chang S, Lin J, Lin T, Liang W . Loss of heterozygosity: an independent prognostic factor of colorectal cancer. World J Gastroenterol. 2005; 11(6):778-84. PMC: 4250583. DOI: 10.3748/wjg.v11.i6.778. View

11.

Bhuvaneshwar K, Belouali A, Singh V, Johnson R, Song L, Alaoui A . G-DOC Plus - an integrative bioinformatics platform for precision medicine. BMC Bioinformatics. 2016; 17(1):193. PMC: 4851789. DOI: 10.1186/s12859-016-1010-0. View

12.

Tsai M, Fang W, Lin S, Tzeng S, Huang C, Yen S . Mapping of genetic deletions on chromosome 3 in colorectal cancer: loss of 3p25-pter is associated with distant metastasis and poor survival. Ann Surg Oncol. 2011; 18(9):2662-70. DOI: 10.1245/s10434-011-1603-9. View

13.

Olshen A, Venkatraman E, Lucito R, Wigler M . Circular binary segmentation for the analysis of array-based DNA copy number data. Biostatistics. 2004; 5(4):557-72. DOI: 10.1093/biostatistics/kxh008. View

14.

Lopez-Gines C, Cerda-Nicolas M, Gil-Benso R, Pellin A, Lopez-Guerrero J, Callaghan R . Association of chromosome 7, chromosome 10 and EGFR gene amplification in glioblastoma multiforme. Clin Neuropathol. 2005; 24(5):209-18. View

15.

Sheffer M, Bacolod M, Zuk O, Giardina S, Pincas H, Barany F . Association of survival and disease progression with chromosomal instability: a genomic exploration of colorectal cancer. Proc Natl Acad Sci U S A. 2009; 106(17):7131-6. PMC: 2678450. DOI: 10.1073/pnas.0902232106. View

16.

Felicella M, Hagenkord J, Kash S, Powers M, Berger M, Perry A . A common 8q (MYC) amplification detected in a multifocal anaplastic astrocytoma by SNP array karyotyping. Clin Neuropathol. 2012; 31(4):210-5. DOI: 10.5414/np300484. View

17.

Huber W, Carey V, Gentleman R, Anders S, Carlson M, Carvalho B . Orchestrating high-throughput genomic analysis with Bioconductor. Nat Methods. 2015; 12(2):115-21. PMC: 4509590. DOI: 10.1038/nmeth.3252. View

18.

Andersson R, Bruder C, Piotrowski A, Menzel U, Nord H, Sandgren J . A segmental maximum a posteriori approach to genome-wide copy number profiling. Bioinformatics. 2008; 24(6):751-8. DOI: 10.1093/bioinformatics/btn003. View

19.

Orsetti B, Selves J, Bascoul-Mollevi C, Lasorsa L, Gordien K, Bibeau F . Impact of chromosomal instability on colorectal cancer progression and outcome. BMC Cancer. 2014; 14:121. PMC: 4233623. DOI: 10.1186/1471-2407-14-121. View

20.

Wu L, Chipman H, Bull S, Briollais L, Wang K . A Bayesian segmentation approach to ascertain copy number variations at the population level. Bioinformatics. 2009; 25(13):1669-79. DOI: 10.1093/bioinformatics/btp270. View