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Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Somatic copy number alterations (CNAs) play a significant role in the development of this lethal cancer. In this study, we present a meta-analysis of CNAs for a total of 1,395 HNSCC samples. Publicly available R packages and in-house scripts were used for genomic array data processing, including normalization, segmentation and CNA calling. We detected 125 regions of significant gains or losses using GISTIC algorithm and found several potential driver genes in these regions. The incidence of chromothripsis in HNSCC was estimated to be 6%, and the chromosome pulverization hotspot regions were detected. We determined 323 genomic locations significantly enriched for breakpoints, which indicate HNSCC-specific genomic instability regions. Unsupervised clustering of genome-wide CNA data revealed a sub-cluster predominantly composed of nasopharynx tumors and presented a large proportion of HPV-positive samples. These results will facilitate the discovery of therapeutic candidates and extend our molecular understanding of HNSCC.

Triple‑negative breast cancer (TNBC) accounts for ~15% of all breast cancer diagnoses each year. Patients with TNBC tend to have a higher risk for early relapse and a worse prognosis. TNBC is characterized by extensive somatic copy number alterations (CNAs). However, the DNA CNA profile of TNBC remains to be extensively investigated. The present study assessed the genomic profile of CNAs in 201 TNBC samples, aiming to identify recurrent CNAs that may drive the pathogenesis of TNBC. In total, 123 regions of significant amplification and deletion were detected using the Genomic Identification of Significant Targets in Cancer algorithm, and potential driver genes for TNBC were identified. A total of 31 samples exhibited signs of chromothripsis and revealed chromosome pulverization hotspot regions. The present study further determined 199 genomic locations that were significantly enriched for breakpoints, which indicated TNBC‑specific genomic instability regions. Unsupervised hierarchical clustering of tumors resulted in three main subgroups that exhibited distinct CNA profiles, which may reveal the heterogeneity of molecular mechanisms in TNBC subgroups. These results will extend the molecular understanding of TNBC and will facilitate the discovery of therapeutic and diagnostic target candidates.

Chromothripsis is a recently observed phenomenon in cancer cells in which one or several chromosomes shatter into pieces with subsequent inaccurate reassembly and clonal propagation. This type of event generates a potentially vast number of mutations within a relatively short-time period, and has been considered as a new paradigm in cancer development. Despite recent advances, much work is still required to better understand the molecular mechanisms of this phenomenon, and thus an easy-to-use tool is in urgent need for automatically detecting and annotating chromothripsis. Here we present CTLPScanner, a web server for detection of chromothripsis-like pattern (CTLP) in genomic array data. The output interface presents intuitive graphical representations of detected chromosome pulverization region, as well as detailed results in table format. CTLPScanner also provides additional information for associated genes in chromothripsis region to help identify the potential candidates involved in tumorigenesis. To assist in performing meta-data analysis, we integrated over 50 000 pre-processed genomic arrays from The Cancer Genome Atlas and Gene Expression Omnibus into CTLPScanner. The server allows users to explore the presence of chromothripsis signatures from public data resources, without carrying out any local data processing. CTLPScanner is freely available at http://cgma.scu.edu.cn/CTLPScanner/.

Background The integration of DNA methylation and copy number alteration data promises to provide valuable insight into the underlying molecular mechanisms responsible for cancer initiation and progression. However, the generation and processing of these datasets are costly and time-consuming if carried out separately. The Illumina Infinium HumanMethylation450 BeadChip, initially designed for the evaluation of DNA methylation levels, allows copy number variant calling using bioinformatics tools. Results A substantial amount of Infinium HumanMethylation450 data across various cancer types has been accumulated in recent years and is a valuable resource for large-scale data analysis. Here we present MethCNA, a comprehensive database for genomic and epigenomic data integration in human cancer. In the current release, MethCNA contains about 10,000 tumor samples representing 37 cancer types. All raw array data were collected from The Cancer Genome Atlas and NCBI Gene Expression Omnibus database and analyzed using a pipeline that integrated multiple computational resources and tools. The normalized copy number aberration data and DNA methylation alterations were obtained. We provide a user-friendly web-interface for data mining and visualization. Conclusions The Illumina Infinium HumanMethylation450 BeadChip enables the interrogation and integration of both genomic and epigenomic data from exactly the same DNA specimen, and thus can aid in distinguishing driver from passenger mutations in cancer. We expect MethCNA will enable researchers to explore DNA methylation and copy number alteration patterns, identify key oncogenic drivers in cancer, and assist in the development of targeted therapies. MethCNA is publicly available online at http://cgma.scu.edu.cn/MethCNA. Electronic supplementary material The online version of this article (10.1186/s12864-018-4525-0) contains supplementary material, which is available to authorized users.

Accurate detection of chromothripsis event is important to study the mechanisms underlying this phenomenon. CTLPScanner ( http://cgma.scu.edu.cn/CTLPScanner/ ) is a web-based tool for identification and annotation of chromothripsis-like pattern (CTLP) in genomic array data. In this chapter, we illustrate the utility of CTLPScanner for screening chromosome pulverization regions and give interpretation of the results. The web interface offers a set of parameters and thresholds for customized screening. We also provide practical recommendations for effective chromothripsis detection. In addition to the user data processing module, CTLPScanner contains more than 50,000 preprocessed oncogenomic arrays, which allow users to explore the presence of chromothripsis signatures from public data resources.

ChromothripsisDB ( http://cgma.scu.edu.cn/ChromothripsisDB ) is a manually curated database containing a unified description of published chromothripsis cases and relevant genomic aberrations. Available data includes copy number alterations, chromosome structural variations, and gene annotations. The criteria used for detecting chromothripsis in each study are also provided. At present, the molecular mechanisms involved in chromothripsis phenomenon are not fully understood. Thus, further studies with large number of identified chromothripsis samples are needed. The current release of ChromothripsisDB contains more than 400 patient samples, representing over 100 research articles. It represents an extraordinary resource for mining the existing knowledge of chromothripsis.

Summary: Chromothripsis is a single catastrophic event that can lead to massive genomic rearrangements confined to one or a few chromosomes. It provides an alternative paradigm in cancer development and changes the conventional view that cancer develops in a stepwise progression. The mechanisms underlying chromothripsis and their specific impact on tumorigenesis are still poorly understood, and further examination of a large number of identified chromothripsis samples is needed. Unfortunately, this data are difficult to access, as they are scattered across multiple publications, come in different formats and descriptions, or are hidden in figures and supplementary materials. To improve access to this data and promote meta-analysis, we developed ChromothripsisDB, a manually curated database containing a unified description of all published chromothripsis cases and relevant genomic aberrations. Currently, 423 chromothripsis samples representing 107 research articles are included in our database. ChromothripsisDB represents an extraordinary resource for mining the existing knowledge of chromothripsis, and will facilitate the identification of mechanisms involved in this phenomenon. Availability and implementation: ChromothripsisDB is freely available at http://cgma.scu.edu.cn/ChromothripsisDB. Contact: haoyang.cai@scu.edu.cn Supplementary information: Supplementary data are available at Bioinformatics online.

At the onset of lactation, there are three distinct stages of mammary tissue development and function including mammogenesis, colostrogenesis, and lactogenesis. The mechanism of the transition from colostrogenesis to lactogenesis of Maiwa Yak is still unknown. In this study, mammary tissues from three Maiwa Yaks were collected at 1 and 30 d after parturition for transcriptome exploration using Affymetrix Bovine Genome Arrays. Comparing 1 and 30 d results, a total of 517 annotated differentially expressed genes (DEGs) were identified at the criteria of a P ≤ 0.05. The ratio of up-regulated genes to the down-regulated ones was around 1:2 (more specifically, 164:353). To depict the profile of DEGs, a dynamic impact approach (DIA) was used to analyse the microarray data based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. GO terms “fatty acid transport” and “monocarboxylic acid transport” were significantly induced during the colostrum period. The strongly impacted KEGG pa...

Background DNA copy number profiles from microarray and sequencing experiments sometimes contain wave artefacts which may be introduced during sample preparation and cannot be removed completely by existing preprocessing methods. Besides, large derivative log ratio spread (DLRS) of the probes correlating with poor DNA quality is sometimes observed in genome screening experiments and may lead to unreliable copy number profiles. Depending on the extent of these artefacts and the resulting misidentification of copy number alterations/variations (CNA/CNV), it may be desirable to exclude such samples from analyses or to adapt the downstream data analysis strategy accordingly. Results Here, we propose a method to distinguish reliable genomic copy number profiles from those containing heavy wave artefacts and/or large DLRS. We define four features that adequately summarize the copy number profiles for reliability assessment, and train a classifier on a dataset of 1522 copy number profiles from various microarray platforms. The method can be applied to predict the reliability of copy number profiles irrespective of the underlying microarray platform and may be adapted for those sequencing platforms from which copy number estimates could be computed as a piecewise constant signal. Further details can be found at https://github.com/baudisgroup/CNARA. Conclusions We have developed a method for the assessment of genomic copy number profiling data, and suggest to apply the method in addition to and after other state-of-the-art noise correction and quality control procedures. CNARA could be instrumental in improving the assessment of data used for genomic data mining experiments and support the reliable functional attribution of copy number aberrations especially in cancer research. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-3074-7) contains supplementary material, which is available to authorized users.

Objectives MicroRNAs (miRNAs) are endogenous ~23 nucleotides (nt) RNAs, regulating gene expression by pairing to the mRNAs of protein-coding genes to direct their post-transcriptional repression. Both in normal and aberrant activities, miRNAs contribute to a recurring paradigm of cellular behaviors in pathological settings, especially in gerontology. Autophagy, a multi-step lysosomal degradation process with function to degrade long-lived proteins and damaged organelles, has significant impact on gerontology. Thus, elucidating how miRNAs participate in autophagy may enlarge the scope of miRNA in autophagy and facilitate researches in gerontology. Materials and methods Herein, based upon the published studies, predicted targets and gerontology-related diseases, we constructed a web resource named Gerontology-Autophagic-MicroRNA Database (GAMDB) (http://gamdb.liu-lab.com/index.php), which contained 836 autophagy-related miRNAs, 197 targeted genes/proteins and 56 aging-related diseases such as Parkinson' disease, Alzheimer's disease and Huntington's disease. Results and Conclusion We made use of large amounts of data to elucidate the intricate relationships between microRNA-regulated autophagic mechanisms and gerontology. This database will facilitate better understanding of autophagy regulation network in gerontology and thus promoting gerontology-related therapy in the future.

Objectives Autophagy, a highly conserved lysosomal degradation process in eukaryotic cells, can digest long-lived proteins and damaged organelles through vesicular trafficking pathways. Nowadays, mechanisms of autophagy have been gradually elucidated and thus the discovery of small-molecule drugs targeting autophagy has always been drawing much attention. So far, some autophagy-related web servers have been available online to facilitate scientists to obtain the information relevant to autophagy conveniently, such as HADb, CTLPScanner, iLIR server and ncRDeathDB. However, to the best of our knowledge, there is not any web server available about the autophagy-modulating compounds. Methods According to published articles, all the compounds and their relations with autophagy were anatomized. Subsequently, an online Autophagic Compound Database (ACDB) (http://www.acdbliulab.com/) was constructed, which contained information of 357 compounds with 164 corresponding signalling pathways and potential targets in different diseases. Results We achieved a great deal of information of autophagy-modulating compounds, including compounds, targets/pathways and diseases. ACDB is a valuable resource for users to access to more than 300 curated small-molecule compounds correlated with autophagy. Conclusions Autophagic compound database will facilitate to the discovery of more novel therapeutic drugs in the near future.