Institute of Bioinformatics and Biotechnology

Natal, Brazil

Institute of Bioinformatics and Biotechnology

Natal, Brazil

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Kroll J.E.,Institute of Bioinformatics and Biotechnology | Kroll J.E.,Brain Institute | de Souza S.J.,Brain Institute | de Souza G.A.,Institute of Bioinformatics and Biotechnology | de Souza G.A.,University of Oslo
PeerJ | Year: 2014

Integration of transcriptome data is a crucial step for the identification of rare protein variants in mass-spectrometry (MS) data with important consequences for all branches of biotechnology research. Here, we used Splooce, a database of splicing variants recently developed by us, to search MS data derived from a variety of human tumor cell lines. More than 800 new protein variants were identified whose corresponding MS spectra were specific to protein entries from Splooce. Although the types of splicing variants (exon skipping, alternative splice sites and intron retention) were found at the same frequency as in the transcriptome, we observed a large variety of modifications at the protein level induced by alternative splicing events. Surprisingly, we found that 40% of all protein modifications induced by alternative splicing led to the use of alternative translation initiation sites. Other modifications include frameshifts in the open reading frame and inclusion or deletion of peptide sequences. To make the dataset generated here available to the community in a more effective form, the Splooce portal (http://www.bioinformatics-brazil.org/splooce) was modified to report the alternative splicing events supported by MS data. © 2014 Kroll et al.


Kroll J.E.,Institute of Bioinformatics and Biotechnology | De Souza J.E.,Institute of Bioinformatics and Biotechnology | Stransky B.,Federal University of ABC | De Souza G.A.,University of Oslo | De Souza S.J.,Federal University of Rio Grande do Norte
Proceedings - 2012 IEEE 2nd Conference on Healthcare Informatics, Imaging and Systems Biology, HISB 2012 | Year: 2012

Alternative splicing events (AS) is one of the most significant components behind the complexity of multi-cellular organisms. Most, if not all, multi-exonic human genes undergo AS. Many AS events are involved in the etiology of cancer, among many other common human disorders. The emergence of next-generation sequencing offers a unique opportunity to explore the variability generated by AS at an exhaustive way. Furthermore, recent developments is new mass-spectometry platforms has allowed a deeper survey of the human proteome. Here, an analysis of intron retention, the most rare type of AS, was performed integrating transcriptome and proteome data. Intron retention events were evaluated in relation to several features, focusing whether they have biological significance or whether they are just spurius products from the splicing machinery. For the transcriptome analysis, the following dataset was used: 30,678 RefSeqs, 258,444 mRNAs, 6,987,423 ESTs and 9,565,439 sequences derived from NGS. For the proteome analysis, data from Geiger et al., MCP, 2012 was used. We were able to detect an intron retention event for 48% of all human genes. Confirming a previous publication from our group (Galante et al., RNA 2004), these events are enriched at the 3'and 5'untranslated regions (UTRs). Retained introns were significantly enriched with coding potential, which supports a biological role for these events. Furthermore, they were enriched for targets of microRNAs, suggesting a role of this type of AS in the regulation of expression induced by these non-coding RNAs. A significant number of events were detected at the proteome level. This information was integrated together with transcriptome data to further explore the role of intron retention in many biological phenomena. © 2012 IEEE.


Hickman O.J.,King's College London | Smith R.A.,King's College London | Dasgupta P.,King's College London | Narayana Rao S.,Genotypic Technology Pvt Ltd | And 6 more authors.
British Journal of Cancer | Year: 2016

Background: WFDC1/Prostate stromal 20 (ps20) is a small secreted protein highly expressed within the prostate stroma. WFDC1/ps20 expression is frequently downregulated or lost in prostate cancer (PCa) and ps20 has demonstrated growth-suppressive functions in numerous tumour model systems, although the mechanisms of this phenomenon are not understood.Methods:Ps20 was cloned and overexpressed in DU145, PC3, LNCaP and WPMY-1 cells. Cellular growth, cell cycle and apoptosis were characterised. WPMY-1 stromal cells expressing ps20 were characterised by transcriptome microarray and the function of WPMY-1 conditioned media on growth of PCa cell lines was assessed.Results:Prostrate stromal 20 expression enhanced the proliferation of LNCaP cells, whereas stromal WPMY-1 cells were inhibited and underwent increased apoptosis. Prostrate stromal 20-expressing WPMY-1 cells secrete a potently proapoptotic conditioned media. Prostrate stromal 20 overexpression upregulates expression of cyclooxygenase-2 (COX-2) in LNCaP and WPMY-1 cells, and induces expression of a growth-suppressive phenotype, which inhibits proliferation of PCa cells by ps20-expressing WPMY-1 conditioned media. This growth suppression was subsequently shown to be dependent on COX-2 function.Conclusions:This work posits that expression of ps20 in the prostate stroma can regulate growth of epithelial and other tissues through the prostaglandin synthase pathway, and thereby restricts development and progression of neoplasms. This provides a rational for selective pressure against ps20 expression in tumour- associated stroma. © 2016 Cancer Research UK.


De Souza J.E.S.,Institute of Bioinformatics and Biotechnology | De Souza J.E.S.,University of Sao Paulo | De Souza J.E.S.,International Research Center | Fonseca A.F.,Institute of Bioinformatics and Biotechnology | And 7 more authors.
PLoS ONE | Year: 2014

A new method, which allows for the identification and prioritization of predicted cancer genes for future analysis, is presented. This method generates a gene-specific score called the "S-Score" by incorporating data from different types of analysis including mutation screening, methylation status, copy-number variation and expression profiling. The method was applied to the data from The Cancer Genome Atlas and allowed the identification of known and potentially new oncogenes and tumor suppressors associated with different clinical features including shortest term of survival in ovarian cancer patients and hormonal subtypes in breast cancer patients. Furthermore, for the first time a genome-wide search for genes that behave as oncogenes and tumor suppressors in different tumor types was performed. We envisage that the S-score can be used as a standard method for the identification and prioritization of cancer genes for follow-up studies. © 2014 de Souza et al.


Stransky B.,Federal University of ABC | de Souza S.J.,Federal University of ABC | de Souza S.J.,Ludwig Institute for Cancer Research | de Souza S.J.,Institute of Bioinformatics and Biotechnology
Frontiers in Physiology | Year: 2013

Tumorigenesis can be seen as an evolutionary process, in which the transformation of a normal cell into a tumor cell involves a number of limiting genetic and epigenetic events, occurring in a series of discrete stages. However, not all mutations in a cell are directly involved in cancer development and it is likely that most of them (passenger mutations) do not contribute in any way to tumorigenesis. Moreover, the process of tumor evolution is punctuated by selection of advantageous (driver) mutations and clonal expansions. Regarding these driver mutations, it is uncertain how many limiting events are required and/or sufficient to promote a tumorigenic process or what are the values associated with the adaptive advantage of different driver mutations. In spite of the availability of high-quality cancer data, several assumptions about the mechanistic process of cancer initiation and development remain largely untested, both mathematically and statistically. Here we review the development of recent mathematical/computational models and discuss their impact in the field of tumor biology. © 2013 Stransky and de Souza.


Satpute S.K.,University of Pune | Banat I.M.,University of Ulster | Dhakephalkar P.K.,Agharkar Research Institute | Banpurkar A.G.,University of Pune | And 2 more authors.
Biotechnology Advances | Year: 2010

Marine biosphere offers wealthy flora and fauna, which represents a vast natural resource of imperative functional commercial grade products. Among the various bioactive compounds, biosurfactant (BS)/bioemulsifiers (BE) are attracting major interest and attention due to their structural and functional diversity. The versatile properties of surface active molecules find numerous applications in various industries. Marine microorganisms such as Acinetobacter, Arthrobacter, Pseudomonas, Halomonas, Myroides, Corynebacteria, Bacillus, Alteromonas sp. have been studied for production of BS/BE and exopolysaccharides (EPS). Due to the enormity of marine biosphere, most of the marine microbial world remains unexplored. The discovery of potent BS/BE producing marine microorganism would enhance the use of environmental biodegradable surface active molecule and hopefully reduce total dependence or number of new application oriented towards the chemical synthetic surfactant industry. Our present review gives comprehensive information on BS/BE which has been reported to be produced by marine microorganisms and their possible potential future applications. © 2010 Elsevier Inc.


Joshi B.N.,Institute of Bioinformatics and Biotechnology | Bhat M.,Institute of Bioinformatics and Biotechnology | Kothiwale S.K.,Institute of Bioinformatics and Biotechnology | Tirmale A.R.,Institute of Bioinformatics and Biotechnology | Bhargava S.Y.,University of Pune
Evidence-based Complementary and Alternative Medicine | Year: 2011

Diabetes mellitus is a metabolic syndrome characterized by an increase in the blood glucose level. Treatment of diabetes is complicated due to multifactorial nature of the disease. Azadirachta indica Adr. Juss and Bougainvillea spectabilis are reported to have medicinal values including antidiabetic properties. In the present study using in vivo diabetic murine model, A. indica and B. spectabilis chloroform, methanolic and aqueous extracts were investigated for the biochemical parameters important for controlling diabetes. It was found that A. indica chloroform extract and B. spectabilis aqueous, methanolic extracts showed a good oral glucose tolerance and significantly reduced the intestinal glucosidase activity. Interestingly, A. indica chloroform and B. spectabilis aqueous extracts showed significant increase in glucose-6-phosphate dehydrogenase activity and hepatic, skeletal muscle glycogen content after 21 days of treatment. In immunohistochemical analysis, we observed a regeneration of insulin-producing cells and corresponding increase in the plasma insulin and c-peptide levels with the treatment of A. indica chloroform and B. spectabilis aqueous, methanolic extracts. Analyzing the results, it is clear that A. indica chloroform and B. spectabilis aqueous extracts are good candidates for developing new neutraceuticals treatment for diabetes. Copyright 2011 Menakshi Bhat et al.


Kroll J.E.,Institute of Bioinformatics and Biotechnology | Kroll J.E.,Federal University of Rio Grande do Norte | Kim J.,University of California at San Diego | Ohno-Machado L.,University of California at San Diego | de Souza S.J.,Federal University of Rio Grande do Norte
PeerJ | Year: 2015

Motivation. Alternative splicing events (ASEs) are prevalent in the transcriptome of eukaryotic species and are known to influence many biological phenomena. The identification and quantification of these events are crucial for a better understanding of biological processes. Next-generation DNA sequencing technologies have allowed deep characterization of transcriptomes and made it possible to address these issues. ASEs analysis, however, represents a challenging task especially when many different samples need to be compared. Some popular tools for the analysis of ASEs are known to report thousands of events without annotations and/or graphical representations. A new tool for the identification and visualization of ASEs is here described, which can be used by biologists without a solid bioinformatics background. Results. A software suite named Splicing Express was created to perform ASEs analysis from transcriptome sequencing data derived from next-generation DNA sequencing platforms. Its major goal is to serve the needs of biomedical researchers who do not have bioinformatics skills. Splicing Express performs automatic annotation of transcriptome data (GTF files) using gene coordinates available from the UCSC genome browser and allows the analysis of data from all available species. The identification of ASEs is done by a known algorithm previously implemented in another tool named Splooce. As a final result, Splicing Express creates a set of HTML files composed of graphics and tables designed to describe the expression profile of ASEs among all analyzed samples. By using RNA-Seq data fromthe Illumina Human BodyMap and the Rat BodyMap, we show that Splicing Express is able to performall tasks in a straightforward way, identifying well-known specific events. Availability and Implementation. Splicing Express is written in Perl and is suitable to run only in UNIX-like systems. More details can be found at: http://www. bioinformatics-brazil.org/splicingexpress. © 2015 Kroll et al.


PubMed | Institute of Bioinformatics and Biotechnology
Type: | Journal: Evidence-based complementary and alternative medicine : eCAM | Year: 2012

Diabetes mellitus is a metabolic syndrome characterized by an increase in the blood glucose level. Treatment of diabetes is complicated due to multifactorial nature of the disease. Azadirachta indica Adr. Juss and Bougainvillea spectabilis are reported to have medicinal values including antidiabetic properties. In the present study using invivo diabetic murine model, A. indica and B. spectabilis chloroform, methanolic and aqueous extracts were investigated for the biochemical parameters important for controlling diabetes. It was found that A. indica chloroform extract and B. spectabilis aqueous, methanolic extracts showed a good oral glucose tolerance and significantly reduced the intestinal glucosidase activity. Interestingly, A. indica chloroform and B. spectabilis aqueous extracts showed significant increase in glucose-6-phosphate dehydrogenase activity and hepatic, skeletal muscle glycogen content after 21 days of treatment. In immunohistochemical analysis, we observed a regeneration of insulin-producing cells and corresponding increase in the plasma insulin and c-peptide levels with the treatment of A. indica chloroform and B. spectabilis aqueous, methanolic extracts. Analyzing the results, it is clear that A. indica chloroform and B. spectabilis aqueous extracts are good candidates for developing new neutraceuticals treatment for diabetes.

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