scholarly journals Multi-omics Topic Modeling for Breast Cancer Classification

2021 ◽  
Author(s):  
Filippo Valle ◽  
Matteo Osella ◽  
Michele Caselle
Keyword(s):  
Breast Cancer ◽  
Topic Modeling ◽  
Copy Number ◽  
Messenger Rna ◽  
Copy Number Variations ◽  
Cancer Development ◽  
Omics Data ◽  
Driver Genes ◽  
Block Modeling ◽  
Post Transcriptional Regulation

The integration of transcriptional data with other layers of information, such as the post-transcriptional regulation mediated by microRNAs, can be crucial to identify the driver genes and the subtypes of complex and heterogeneous diseases such as cancer. This paper presents an approach based on topic modeling to accomplish this integration task. More specifically, we show how an algorithm based on a hierarchical version of stochastic block modeling can be naturally extended to integrate any combination of 'omics data. We test this approach on breast cancer samples from the TCGA database, integrating data on messenger RNA, microRNAs and copy number variations. We show that the inclusion of the microRNA layer significantly improves the accuracy of subtype classification. Moreover, some of the hidden structures or ``topics'' that the algorithm extracts actually correspond to genes and microRNAs involved in breast cancer development, and are associated to the survival probability.

scholarly journals Comprehensive Genomic And Epigenomic Analyses on Transcriptomic Regulation In Stomach Adenocarcinoma

2021 ◽  
Author(s):  
Junxing Chen ◽  
Weinan Liu ◽  
Jiabin Du ◽  
Pengcheng Wang ◽  
Jintian Wang ◽  
...  
Keyword(s):  
Copy Number ◽  
Messenger Rna ◽  
Copy Number Variations ◽  
Cancer Development ◽  
Mutation Rates ◽  
Independent Data ◽  
Omics Integration ◽  
Copy Numbers ◽  
Stomach Adenocarcinoma ◽  
Points Of View

Abstract DNA copy number variations (CNVs) and alterations in methylation (MET)-induced transcriptomic dysregulation plays an important role in promoting heterogeneous Stomach adenocarcinoma (STAD) progression. However, the association between DNA MET and CNVs, and the effect of this association during cancer development remain unknown. Altogether 313 STAD specimens had been extracted to examine DNA MET and copy numbers, and to measure messenger RNA (mRNA) expression (EXP). According to our results, copy-number-correlated (CNVcor) genes were remarkably co-regulated with MET-correlated (METcor) ones. Additionally, CNVcor and METcor genes were carried out multi-omics integration, and 3 STAD prognostic subtypes had been identified and verified using the independent data. Typically, the subtype that had higher aggressiveness was found to be associated with reduced PIK3CA, ARID1A, SPECC1, ZFHX3, KMT2D, OBSCN, ZBTB20, FSIP2, RANBP2 and TTN mutation rates, as well as increased JPH3, PLCXD3, and KCNB1 expression. Our results suggested that above mentioned genes played vital parts during invasive STAD development. And results of this comprehensive analyses on transcriptomic regulation at genomic and epigenetic levels facilitate to understand STAD pathology at various points of view, and assist in developing the effective STAD treatment.

scholarly journals Genomic alterations caused by HPV integration in a cohort of Chinese endocervical adenocarcinomas

2021 ◽  
Author(s):  
Wenhui Li ◽  
Wanjun Lei ◽  
Xiaopei Chao ◽  
Xiaochen Song ◽  
Yalan Bi ◽  
...  
Keyword(s):  
Copy Number ◽  
Somatic Mutations ◽  
Hpv Infection ◽  
Copy Number Variations ◽  
Cervical Adenocarcinoma ◽  
Structural Variations ◽  
Driver Genes ◽  
Genetic Changes ◽  
Genomic Changes ◽  
Whole Exome

AbstractThe association between human papillomavirus (HPV) integration and relevant genomic changes in uterine cervical adenocarcinoma is poorly understood. This study is to depict the genomic mutational landscape in a cohort of 20 patients. HPV+ and HPV− groups were defined as patients with and without HPV integration in the host genome. The genetic changes between these two groups were described and compared by whole-genome sequencing (WGS) and whole-exome sequencing (WES). WGS identified 2916 copy number variations and 743 structural variations. WES identified 6113 somatic mutations, with a mutational burden of 2.4 mutations/Mb. Six genes were predicted as driver genes: PIK3CA, KRAS, TRAPPC12, NDN, GOLGA6L4 and BAIAP3. PIK3CA, NDN, GOLGA6L4, and BAIAP3 were recognized as significantly mutated genes (SMGs). HPV was detected in 95% (19/20) of patients with cervical adenocarcinoma, 7 of whom (36.8%) had HPV integration (HPV+ group). In total, 1036 genes with somatic mutations were confirmed in the HPV+ group, while 289 genes with somatic mutations were confirmed in the group without HPV integration (HPV− group); only 2.1% were shared between the two groups. In the HPV+ group, GOLGA6L4 and BAIAP3 were confirmed as SMGs, while PIK3CA, NDN, KRAS, FUT1, and GOLGA6L64 were identified in the HPV− group. ZDHHC3, PKD1P1, and TGIF2 showed copy number amplifications after HPV integration. In addition, the HPV+ group had significantly more neoantigens. HPV integration rather than HPV infection results in different genomic changes in cervical adenocarcinoma.

Cancer Target Gene Screening: a web application for breast cancer target gene screening using multi-omics data analysis

2019 ◽  
Vol 21 (2) ◽  
pp. 663-675 ◽  
Author(s):  
Hyung-Yong Kim ◽  
Hee-Joo Choi ◽  
Jeong-Yeon Lee ◽  
Gu Kong
Keyword(s):  
Breast Cancer ◽  
Web Application ◽  
Target Gene ◽  
Biological Significance ◽  
Cancer Type ◽  
Omics Data ◽  
Breast Cancer Patients ◽  
Driver Genes ◽  
Cancer Driver ◽  
Gene Screening

Abstract Breast cancer comprises several molecular subtypes with distinct clinical features and treatment responses, and a substantial portion of each subtype remains incurable. A comprehensive analysis of multi-omics data and clinical profiles is required in order to better understand the biological complexity of this cancer type and to identify new prognostic and therapeutic markers. Thus, there arises a need for useful analytical tools to assist in the investigation and clinical management of the disease. We developed Cancer Target Gene Screening (CTGS), a web application that provides rapid and user-friendly analysis of multi-omics data sets from a large number of primary breast tumors. It allows the investigation of genomic and epigenomic aberrations, evaluation of transcriptomic profiles and performance of survival analyses and of bivariate correlations between layers of omics data. Notably, the genome-wide screening function of CTGS prioritizes candidate genes of clinical and biological significance among genes with copy number alteration, DNA methylation and dysregulated expression by the integrative analysis of different types of omics data in customized subgroups of breast cancer patients. These features may help in the identification of druggable cancer driver genes in a specific subtype or the clinical condition of human breast cancer. CTGS is available at http://ctgs.biohackers.net.

scholarly journals Signaling Network Assessment of Mutations and Copy Number Variations Predict Breast Cancer Subtype-Specific Drug Targets

Cell Reports ◽  
2013 ◽  
Vol 5 (1) ◽  
pp. 216-223 ◽  
Author(s):  
Naif Zaman ◽  
Lei Li ◽  
Maria Luz Jaramillo ◽  
Zhanpeng Sun ◽  
Chabane Tibiche ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Copy Number ◽  
Drug Targets ◽  
Breast Cancer Subtype ◽  
Copy Number Variations ◽  
Signaling Network ◽  
Specific Drug ◽  
Cancer Subtype

Detection of Copy Number Variations in Breast Cancer Samples Using Single-nucleotide Polymorphism-targeted Massively Multiplexed PCR

2014 ◽  
Vol 207 (6) ◽  
pp. 287
Author(s):  
Joshua E. Babiarz ◽  
Bernhard G. Zimmermann ◽  
Tudor Constantin ◽  
Ryan Swenerton ◽  
Eser Kirkizlar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Single Nucleotide Polymorphism ◽  
Copy Number ◽  
Copy Number Variations ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Multiplexed Pcr

Non-invasive Cell-free Tumor DNA-based Detection of Breast Cancer-related Copy Number Variations

2014 ◽  
Vol 207 (6) ◽  
pp. 287-288
Author(s):  
Bernhard G. Zimmermann ◽  
Eser Kirkizlar ◽  
Matthew Hill ◽  
Tudor Constantin ◽  
Styrmir Sigurjonsson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Copy Number ◽  
Copy Number Variations ◽  
Non Invasive ◽  
Invasive Cell ◽  
Tumor Dna

scholarly journals Germline copy number variations are associated with breast cancer risk and prognosis

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Mahalakshmi Kumaran ◽  
Carol E. Cass ◽  
Kathryn Graham ◽  
John R. Mackey ◽  
Roland Hubaux ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Copy Number ◽  
Copy Number Variations

scholarly journals Comprehensive Analysis of Metabolic Genes in Breast Cancer Based on Multi-Omics Data

2021 ◽  
Vol 27 ◽  
Author(s):  
Yu Hua ◽  
Lihong Gao ◽  
Xiaobo Li
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Arachidonic Acid ◽  
Copy Number Variation ◽  
Immune Cells ◽  
Copy Number ◽  
Clinical Parameters ◽  
Omics Data ◽  
Metabolic Genes ◽  
Number Variation

Background: Reprogramming of cell metabolism is one of the most important hallmarks of breast cancer. This study aimed to comprehensively analyze metabolic genes in the initiation, progression, and prognosis of breast cancer.Materials and Methods: Data from The Cancer Genome Atlas (TCGA) in breast cancer were downloaded including RNA-seq, copy number variation, mutation, and DNA methylation. A gene co-expression network was constructed by the weighted correlation network analysis (WGCNA) package in R. Association of metabolic genes with tumor-related immune cells and clinical parameters were also investigated.Results: We summarized 3,620 metabolic genes and observed mutations in 2,964 genes, of which the most frequently mutated were PIK3CA (51%), TNN (26%), and KMT2C (15%). Four genes (AKT1, ERBB2, KMT2C, and USP34) were associated with survival of breast cancer. Significant association was detected in the tumor mutation burden (TMB) of metabolic genes with T stage (p = 0.045) and N stage (p = 0.004). Copy number variations were significantly associated with recurrence and prognosis of breast cancer. The co-expression network for differentially expressed metabolic genes by WGCNA suggested that the modules were associated with glycerophospholipid, arachidonic acid, carbon, glycolysis/gluconeogenesis, and pyrimidine/purine metabolism. Glycerophospholipid metabolism correlated with most of the immune cells, while arachidonic acid metabolism demonstrated a significant correlation with endothelial cells. Methylation and miRNA jointly regulated 14 metabolic genes while mutation and methylation jointly regulated PIK3R1.Conclusion: Based on multi-omics data of somatic mutation, copy number variation, mRNA expression, miRNA expression, and DNA methylation, we identified a series of differentially expressed metabolic genes. Metabolic genes are associated with tumor-related immune cells and clinical parameters, which might be therapy targets in future clinical application.

scholarly journals Comprehensive Genomic Analysis Reveals the Prognostic Role of LRRK2 Copy-Number Variations in Human Malignancies

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 846
Author(s):  
Gianluca Lopez ◽  
Giulia Lazzeri ◽  
Alessandra Rappa ◽  
Giuseppe Isimbaldi ◽  
Fulvia Milena Cribiù ◽  
...  
Keyword(s):  
Copy Number ◽  
Prognostic Significance ◽  
Point Mutations ◽  
Genomic Analysis ◽  
Genetic Alterations ◽  
Copy Number Variations ◽  
Cancer Development ◽  
Future Research ◽  
Gene Deletions ◽  
Significant Difference

Genetic alterations of leucine-rich repeat kinase 2 (LRRK2), one of the most important contributors to familial Parkinson’s disease (PD), have been hypothesized to play a role in cancer development due to demographical and preclinical data. Here, we sought to define the prevalence and prognostic significance of LRRK2 somatic mutations across all types of human malignancies by querying the publicly available online genomic database cBioPortal. Ninety-six different studies with 14,041 cases were included in the analysis, and 761/14,041 (5.4%) showed genetic alterations in LRRK2. Among these, 585 (76.9%) were point mutations, indels or fusions, 168 (22.1%) were copy number variations (CNVs), and 8 (1.0%) showed both types of alterations. One case showed the somatic mutation R1441C. A significant difference in terms of overall survival (OS) was noted between cases harboring somatic LRRK2 whole deletions, amplifications, and CNV-unaltered cases (median OS: 20.09, 57.40, and 106.57 months, respectively; p = 0.0008). These results suggest that both LRRK2 amplifications and whole gene deletions could play a role in cancer development, paving the way for future research in terms of potential treatment with LRRK2 small molecule inhibitors for LRRK2-amplified cases.

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