scholarly journals Analysis of Array-CGH Data Using the R and Bioconductor Software Suite

2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Winfried A. Hofmann ◽  
Anja Weigmann ◽  
Marcel Tauscher ◽  
Britta Skawran ◽  
Tim Focken ◽  
...  
Keyword(s):  
Array Cgh ◽  
Molecular Genetic ◽  
Comparative Genomic ◽  
Accurate Identification ◽  
Genome Wide ◽  
Versatile Tool ◽  
Breakpoint Detection ◽  
Dna Copy Number Alterations ◽  
User Friendly

Background. Array-based comparative genomic hybridization (array-CGH) is an emerging high-resolution and high-throughput molecular genetic technique that allows genome-wide screening for chromosome alterations. DNA copy number alterations (CNAs) are a hallmark of somatic mutations in tumor genomes and congenital abnormalities that lead to diseases such as mental retardation. However, accurate identification of amplified or deleted regions requires a sequence of different computational analysis steps of the microarray data.Results. We have developed a user-friendly and versatile tool for the normalization, visualization, breakpoint detection, and comparative analysis of array-CGH data which allows the accurate and sensitive detection of CNAs.Conclusion. The implemented option for the determination of minimal altered regions (MARs) from a series of tumor samples is a step forward in the identification of new tumor suppressor genes or oncogenes.

i6mA-Pred: identifying DNA N6-methyladenine sites in the rice genome

2019 ◽  
Vol 35 (16) ◽  
pp. 2796-2800 ◽  
Author(s):  
Wei Chen ◽  
Hao Lv ◽  
Fulei Nie ◽  
Hao Lin
Keyword(s):  
Dna Sequences ◽  
Rice Genome ◽  
Chemical Properties ◽  
Computational Method ◽  
Accurate Identification ◽  
Feature Selection Technique ◽  
Jackknife Test ◽  
Genome Wide ◽  
Wide Range ◽  
User Friendly

Abstract Motivation DNA N6-methyladenine (6mA) is associated with a wide range of biological processes. Since the distribution of 6mA site in the genome is non-random, accurate identification of 6mA sites is crucial for understanding its biological functions. Although experimental methods have been proposed for this regard, they are still cost-ineffective for detecting 6mA site in genome-wide scope. Therefore, it is desirable to develop computational methods to facilitate the identification of 6mA site. Results In this study, a computational method called i6mA-Pred was developed to identify 6mA sites in the rice genome, in which the optimal nucleotide chemical properties obtained by the using feature selection technique were used to encode the DNA sequences. It was observed that the i6mA-Pred yielded an accuracy of 83.13% in the jackknife test. Meanwhile, the performance of i6mA-Pred was also superior to other methods. Availability and implementation A user-friendly web-server, i6mA-Pred is freely accessible at http://lin-group.cn/server/i6mA-Pred.

scholarly journals First Report of a de novo 10q23.31q23.33 Microdeletion: Obesity, Intellectual Disability and Microcephaly

2021 ◽  
pp. 1-5
Author(s):  
Ayberk Turkyilmaz ◽  
Erdal Kurnaz ◽  
Atilla Cayir
Keyword(s):  
Intellectual Disability ◽  
Array Cgh ◽  
De Novo ◽  
Chromosomal Abnormalities ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Autism Spectrum ◽  
Comparative Genomic ◽  
Facial Dysmorphism ◽  
Genetic And Environmental Factors

Intellectual disability (ID) is characterized by limited or insufficient development of mental abilities, including intellectual functioning impairments, such as learning and understanding cause-effect relationships. Some cases have ID as the only finding and are called isolated cases. Conversely, cases accompanied by facial dysmorphism, microcephaly, autism spectrum disorder, epilepsy, obesity, and congenital anomalies are called syndromic developmental delay (DD)/ID. Isolated and syndromic DD/ID cases show extreme genetic heterogeneity. Genetic etiology can be detected in approximately 40% of the cases, whereas chromosomal abnormalities are observed in 25%. Obesity is a multifactorial disease in which both genetic and environmental factors play important roles. The role of heredity in obesity has been reported to be between 40 and 70%. Array-based comparative genomic hybridization (array-CGH) can detect CNVs in the whole genome at a higher resolution than conventional cytogenetic methods. Array-CGH is currently recommended as the first-tier genetic test for ID cases worldwide. In the present study, we aimed to evaluate clinical, radiological, and genetic analyses of a 12-year and 4-month-old girl with microcephaly, ID, and obesity. In the array-CGH analysis, a 3.1-Mb deletion, arr[GRGh37] 10q23.31g23.33 (92745793_95937944)×1 was detected, and this alteration was evaluated to be pathogenic. We consider that haploinsufficiency of the candidate genes (<i>GPR120</i>, <i>KIF11</i>, <i>EXOC6</i>, <i>CYP26A1</i>, <i>CYP26C1</i>, and <i>LGI1</i>) in the deletion region may explain microcephaly, ID, obesity, seizures, and ophthalmological findings in our patient. The investigation of 10q23.31q23.33 microdeletion in cases with syndromic obesity may contribute to molecular genetic diagnosis.

Acute Lymphoblastic Leukemia with “Normal” Karyotype is not without Genomic Aberrations.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1491-1491
Author(s):  
Anu Usvasalo ◽  
Riikka Räty ◽  
Arja Harila-Saari ◽  
Pirjo Koistinen ◽  
Eeva-Riitta Savolainen ◽  
...  
Keyword(s):  
T Cell ◽  
Copy Number ◽  
Array Cgh ◽  
Receptor Gene ◽  
Molecular Genetic ◽  
Normal Karyotype ◽  
Cell Receptor ◽  
T Cell Receptor Gene ◽  
Conventional Cytogenetics ◽  
Dna Copy Number Alterations

Abstract Development of cytogenetic methods has contributed to the understanding that ALL is not a homogenous disease. Detection of structural and numerical alterations in the chromosomes of lymphoblasts has identified several different ALL subgroups. G-banding reveals about 60–70% of these changes. The development of FISH and PCR methods has decreased the proportion of apparently normal karyotype to less than 20%. Still a part of ALL patients have no chromosomal aberrations detected with conventional cytogenetics. It seems likely, however, that ALL with a normal karyotype reflects rather our inadequate capability to detect all possible aberrations than a true normality of the lymphoblast genome. Microarray methods offer an effective tool to define novel cytogenetic changes in ALL. In our study characterizing and evaluating ALL in adolescents and young adults aged 10–25 years in Finland, we analyzed patients diagnosed during 1990–2007 (n=231). Eighty-nine patients had normal (n=80) or failed (n=9) karyotype at diagnosis. DNA from initial samples was available for 27 of these 89 patients. 26 patients had normal karyotypes, for one patient the karyotype analysis failed by G-banding at diagnosis. The key clinical characteristics of the 27 patients did not differ from the rest of the patients with normal or failed karyotype. Genomic DNA was extracted from diagnostic bone marrow samples. Digestion, labeling and hybridization of DNA was performed according to the Agilent protocol version 2.0 for 44K arrays. Labeled samples were hybridized against gender matched reference DNAs to Human Genome CGH 44B oligo microarray slides (Agilent Technologies Santa Clara, CA, USA). For data-analysis Agilent’s CGH Analytics software version 3.5 was used. The starting and ending points of the aberrations were confirmed by the ADM-2 algorithm with 10.0 threshold. The immunophenotype of the patients was as follows: T-cell ALL 8/27 patients, precursor B ALL 13/27, mixed lineage 5/27 (according to the European Group for the Immunological Characterization of Leukemias), not known 1/27. Seventeen patients had normal karyotype and no other marker for MRD follow-up, while 9 patients had either immunoglobulin and/or T-cell receptor gene rearrangement (n=8) or over-expression of Willms Tumor gene 1 (WT1) (n=1). In total 58 aberrations were detected in the 27 patient samples (1–7 aberrations per sample, mean 2.1) (Figure 1). Four samples (15%) did not show any aberration (two with immunoglobulin and/or T-cell receptor gene rearrangements). Losses were detected in 20/27 cases and gains in 10/27 cases. Cases with losses only were more frequent (n=13, 48%) than those with gains only (n=3, 11%). Losses were more numerous than gains (44/20 vs. 14/10). Single aberrations were seen in seven patients. Five of these were deletions affecting 9p21.3, two were gains in 21q. In the 27 cases, the most commonly detected aberrations were deletions involving 9p21.3 (n=10), 5/10 (50%) being T-ALL. In all the 10 cases the CDKN2A gene was affected. Other aberrations seen more than once were deletion of 6q (n=4), amplification of the terminal part of 21q (n=3), amplification of 1q (n=2), deletion of 12p (n=2), deletion in 12q23-q24 (n=2), deletion in 16q22 (n=2), deletion in 17q11 (n=2) and deletion in 22q11 (n=2). Nineteen relatively small aberrations (about 2 Mb or less in size) were detected in 15 cases and such deletion was found to be the only aberration in 4/15 cases. Our data indicate that a subgroup of ALL with fully normal cytogenetics may not exist. Microarray CGH shows a clear benefit in more detailed examination of the blast cell DNA. In 85% (23/27) of the patients with initially normal karyotypes we determined single or multiple aberrations with array CGH. Losses were more frequent than gains. Seven patients (26%) had only a single aberration, three of these being submicroscopic (&lt;200 kb).We conclude that microarray CGH enables to detect molecular-genetic changes also in ALL cases having a “normal” karyotype using conventional cytogenetics. We are getting closer to the point where normal molecular-genetic findings do not exist in leukemic lymphoblasts. Figure 1. DNA copy number alterations detected with array CGH in 27 adolescent ALL patients with initially normal or failed karyotype. Vertical lines to the left and right of each chromosome represents copy number losses and gains, respectively. Figure 1. DNA copy number alterations detected with array CGH in 27 adolescent ALL patients with initially normal or failed karyotype. Vertical lines to the left and right of each chromosome represents copy number losses and gains, respectively.

DETECTING AND ANALYZING COPY NUMBER ALTERNATIONS IN ARRAY-BASED CGH DATA

2016 ◽  
Vol 28 (06) ◽  
pp. 1650044 ◽  
Author(s):  
Mariam A. Sheha ◽  
Mai S. Mabrouk ◽  
Mahmoud Elhefnawi
Keyword(s):  
Copy Number ◽  
Genomic Dna ◽  
Array Cgh ◽  
Artificial Chromosome ◽  
Gaussian Mixture ◽  
Comparative Genomic ◽  
Intensity Ratios ◽  
Dna Copy Number Alterations ◽  
Copy Number Changes ◽  
Tissue Specimens

Copy number changes or alterations are a form of genetic variation in the human genome. Genomic DNA copy number alterations (CNAs) are associated with the development and progression of cancers. Array-based comparative genomic hybridization (a-CGH) is a technique used to identify copy number changes in genomic DNA. It yields data consisting of fluorescence intensity ratios of test and reference DNA samples. The intensity ratios provide information about the number of copies in DNA. Practical issues such as the contamination of tumor cells in tissue specimens and normalization errors necessitate the use of automated statistics algorithms for learning about the genomic alterations from array CGH data. Specifically, there is a need for algorithms that can identify gains and losses in the number of copies based on statistical considerations, rather than merely detect trends in the data. For this purpose the proposed study introduces three different approaches; Circular binary segmentation, Bayesian approach, relying on the hidden Markov model and effective Gaussian mixture (GM) clustering for the analysis of array CGH profiles. Publicly available data on pancreatic adenocarcinoma and Coriell cell line bacterial artificial chromosome (BAC) array were used for the analysis to illustrate the reliability and success of the techniques.

Array-Based Comparative Genomic Hybridization for Genome-Wide Analysis of DNA Copy Number in Myelodysplastic Syndromes.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3420-3420
Author(s):  
Masashi Sanada ◽  
Yasuhito Nanya ◽  
Akira Hangaishi ◽  
Noriko Hosoya ◽  
LiLi Wang ◽  
...  
Keyword(s):  
Human Genome ◽  
Tumor Cells ◽  
Copy Number ◽  
Large Scale ◽  
Array Cgh ◽  
Chromosomal Abnormalities ◽  
Comparative Genomic ◽  
Normal Cells ◽  
Genome Wide Analysis ◽  
Genome Wide

Abstract Myelodysplastic syndrome(MDS)is a clonal disorder of hematopoietic stem cells characterized by ineffective hematopoiesis and propensity to acute myeloid leukemias. The conversion of a normal stem cell into a preleukemic and ultimately leukemic state is thought to be a multistep process requiring accumulation of a number of genetic changes. Conventional cytogenetic analysis has disclosed a number of chromosome abnormalities common to MDS and provided valuable clues to characterize these genetic lesions, rarity of balanced translocations and relative predominance of unbalanced abnormalities in MDS, including gene deletions and amplifications. However conventional analytical methods provide only limited resolutions of analysis for identification of genetic gains and losses and prevent further molecular delineation of relevant genes to the pathogenesis of MDS.&lt;/PRE&gt; Array-based comparative genomic hybridization (CGH) is a robust technique to enable rapid and comprehensive genome-wide analysis of genetic aberrations in cancers, in which differentially labeled DNAs from both tumor and normal samples are comparatively hybridized to a large number of genomic DNAs. In this study, we constructed a high-quality array-based CGH system for genome-wide analysis of chromosomal abnormalities to identify candidate target genes of MDS. Our whole genome arrays consisted of 3,300 BAC/PAC clones, thus having an average resolution of 1.0 Mb over the whole human genome. Each clone was amplified with degenerated oligonucleotide primed-PCR (DOP-PCR) and the amplified products were spotted in duplicate grids onto aminosilan-coated glass slides. For more high-resolution analysis, we employed the GeneChip Mapping 100k arrays (Affymetrix), originally developed for large-scale SNP typing, as a tool for detection of copy number changes in selected MDS cases. It contains 116,204 different SNPs on two separate arrays, covering the whole human genome with an average resolution of 21 kb. With this arrays DNA copy number’s changes could be estimated by comparing intensity of SNP signals of tumor cells with that of normal cells from the same patients. In addition, using paired samples from tumor cells and normal cells, large-scale LOH analysis became also possible.&lt;/PRE&gt; In total, 54 MDS samples were analyzed using our array CGH system. In addition to large chromosomal changes, including loss of 5q, 7q, 13q, and 20q, and gain of the whole chromosome 8, a number of small, cryptic chromosomal abnormalities were identified that would escape from conventional cytogenetic detection. Many of these abnormalities were represented only by a single PAC/BAC clone. In several chromosome regions, including 3q13, 5p15, 13p33, and 20q12, there existed commonly deleted regions, which could be confirmed by FISH analysis. Similarly gains of genetic materials were found on 8p23 and 17p13. Several genes were identified within these regions that may be candidates for relevant genes to these genetic alterations. In conclusion, genome-profiling using array CGH techniques were highly useful tools for delineating the pathogenesis of MDS.&lt;/PRE&gt;

Iterative feature representations improve N4-methylcytosine site prediction

2019 ◽  
Vol 35 (23) ◽  
pp. 4930-4937 ◽  
Author(s):  
Leyi Wei ◽  
Ran Su ◽  
Shasha Luan ◽  
Zhijun Liao ◽  
Balachandran Manavalan ◽  
...  
Keyword(s):  
Feature Space ◽  
Feature Representation ◽  
Supplementary Information ◽  
Accurate Identification ◽  
Feature Representations ◽  
Genome Wide ◽  
A Genome ◽  
Benchmark Datasets ◽  
Sequential Models ◽  
User Friendly

Abstract Motivation Accurate identification of N4-methylcytosine (4mC) modifications in a genome wide can provide insights into their biological functions and mechanisms. Machine learning recently have become effective approaches for computational identification of 4mC sites in genome. Unfortunately, existing methods cannot achieve satisfactory performance, owing to the lack of effective DNA feature representations that are capable to capture the characteristics of 4mC modifications. Results In this work, we developed a new predictor named 4mcPred-IFL, aiming to identify 4mC sites. To represent and capture discriminative features, we proposed an iterative feature representation algorithm that enables to learn informative features from several sequential models in a supervised iterative mode. Our analysis results showed that the feature representations learnt by our algorithm can capture the discriminative distribution characteristics between 4mC sites and non-4mC sites, enlarging the decision margin between the positives and negatives in feature space. Additionally, by evaluating and comparing our predictor with the state-of-the-art predictors on benchmark datasets, we demonstrate that our predictor can identify 4mC sites more accurately. Availability and implementation The user-friendly webserver that implements the proposed 4mcPred-IFL is well established, and is freely accessible at http://server.malab.cn/4mcPred-IFL. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Cytogenomic Evaluation of Subjects with Syndromic and Nonsyndromic Conotruncal Heart Defects

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Karen Regina de Souza ◽  
Rafaella Mergener ◽  
Janaina Huber ◽  
Lucia Campos Pellanda ◽  
Mariluce Riegel
Keyword(s):  
Array Cgh ◽  
Heart Defects ◽  
Copy Number Variations ◽  
Comparative Genomic ◽  
Data Sets ◽  
Comparative Genomic Hybridization Array ◽  
Genomic Databases ◽  
Genomic Imbalances ◽  
Genome Wide ◽  
Line Test

Despite considerable advances in the detection of genomic abnormalities in congenital heart disease (CHD), the etiology of CHD remains largely unknown. CHD is the most common birth defect and is a major cause of infant morbidity and mortality, and conotruncal defects constitute 20% of all CHD cases. We used array comparative genomic hybridization (array-CGH) to retrospectively study 60 subjects with conotruncal defects and identify genomic imbalances. The DNA copy number variations (CNVs) detected were matched with data from genomic databases, and their clinical significance was evaluated. We found that 38.3% (23/60) of CHD cases possessed genomic imbalances. In 8.3% (5/60) of these cases, the imbalances were causal or potentially causal CNVs; in 8.3% (5/60), unclassified CNVs were identified; and in 21.6% (13/60), common variants were detected. Although the interpretation of the results must be refined and there is not yet a consensus regarding the types of CHD cases in which array-CGH should be used as a first-line test, the identification of these CNVs can assist in the evaluation and management of CHD. The results of such studies emphasize the growing importance of the use of genome-wide assays in subjects with CHD to increase the number of genomic data sets associated with this condition.

Multiple Secondary Genetic Events Inducing Histologic Progression (HP) of Non-MALT Marginal Zone Lymphoma (MZL): An Integrated Genomic Analysis of Genome-Wide Copy-Number-Changes (CNC) and Transcriptomic Data.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1198-1198
Author(s):  
Lise Willems ◽  
Josette Briere ◽  
Mahatsangy Raharijaona ◽  
Benoit Ballester ◽  
Samuel Quentin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Array Cgh ◽  
B Cell Lymphoma ◽  
Genetic Alterations ◽  
Integrated Analysis ◽  
Comparative Genomic ◽  
Transcriptomic Data ◽  
Genome Wide ◽  
Cyclin G

Abstract HP of indolent B cell lymphoma to a high grade lymphoma is usually associated with a rapidly progressive clinical course and a short survival. The risk of HP in MZL is evaluated around 10–20%, and can be detected at diagnosis or during the evolution of the disease. No criteria have been yet formally adopted to range HP, even in the more recent OMS classification, although therapeutic impact is important. In this study we wished to determine the genetic alterations implicated in the HP of non-MALT MZL, using an integrated analysis of genome-wide CNC and transcriptomic data. Fresh-frozen tumor biopsies and clinical data were obtained from 66 untreated non-MALT MZL patients of 3 institutions (SLS, HD, CHLS, France). Features reviews including morphologic aspect, immunophenotype, and conventional cytogenetics, classified 52 cases as MZL and 14 cases as MZL with HP (HP-MZL). HP was assessed by the presence of large cells, the presence of cohesive sheets of larges cells, and elevated Ki67. CNC were analysed in 20 splenic MZL (SMZL), in 6 HP-SMZL cases including 2 matched cases, and in 3 germ-line DNA of these cases using array comparative genomic hybridization (array-CGH) (Agilent, 105K). Normalization of the array-CGH data was realized by Lowess correction. Transcriptomic analysis of 32 SMZL and 8 HP-MZL, including 2 matched cases, was performed with a nylon DNA microarray of 9,216 human genes. After Lowess correction, data were visualized by hierarchical clustering allowing to distinguish patterns of gene expression corresponding to precise functions, cell or tissue subtype. The ability of individual transcripts to distinguish MZL and HP-MZL subtypes was calculated using discriminating score and bootstrap resampling. The most common imbalances detected by cytogenetics were gains of 3/3q (n=11/61, 18 %) and 18q (n=13/61, 21%), and deletions in 7q (n=18/61, 17%), and were detected in both groups, SMZL and HP-SMZL. Array-CGH analysis showed that no recurrent CNC was specific of all HP-SMZL. Only 1 CNC was present in 4 of the 6 HP-SMZL cases, 3 in 3 cases, and 29 in 2 cases. These CNC could also be seen in SMZL. Comparing the matched pairs, we identified secondary CNC changes. One was located in 4p and includes 9 genes. Among them, was Cyclin G associated kinase. This CNC was also present in 2 other HP-MZL cases. Another was located in 6p and includes 4 genes, comprising IRF4. Another HP-SMZL case exhibited a HP-SMZL specific CN gain of the oncogene Myc in 8q. These 3 genes are known to be involved in proliferation. Gene expression profiling showed overexpression of genes involved in proliferation and underexpression of p53 in HP-MZL cases compared to SMZL cases. The proliferation signature included PCNA, genes involved in glycolysis (GAPD, LDHA), in cell cycle (CDC10, CDK4), and cell proliferation (TNFRSF13B, MCL1). Two other signatures included genes overexpressed specifically in HP-MZL: one specific to the stroma with MIG, STAT1, Cathepsin B and C, CREG, IGFR2R; and a cluster of unknown function regrouping several oncogenes (DEK, DJ-1), genes related to cell machinery and cell motility (HMMR, PRPF4, PPOX) and genes involved in signal transduction (ZNF146, FLJ10618, PBXL2). In addition to p53, HP-MZL underexpressed genes included PMSB1 in the proteasome, KLF2 and PFC. In conclusion, integrated genetic and transcriptomic analyses of non-MALT MZL and HP-MZL showed that histologic progression was related to the alteration of cell proliferation. Beside chromosomal alterations typical to SMZL, secondary CNC could be detected in HP-SMZL cases. These CNC included genes associated with cell proliferation: Cyclin G associated Kinase, IRF4, and Myc. These results highlight that deregulation of different pathways drive the MZL cells toward a higher proliferative rate charateristic of histologic progression.

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