Navegando por Autor "Kroll, José Eduardo"

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Bioinformatics analysis of the human surfaceome reveals new targets for a variety of tumor types
(Hindawi, 2016-10-18) Fonseca, André L.; Silva, Vandeclécio Lira da; Fonseca, Marbella M.; Meira, Isabella Tanus Job e; Silva, Thayná Emília Oliveira; Kroll, José Eduardo; Ribeiro-dos-Santos, André M.; Freitas, Cléber R.; Furtado, Raimundo; Souza, Jorge Estefano Santana de; Ferreira, Beatriz Stransky; Souza, Sandro José de
It is estimated that 10 to 20% of all genes in the human genome encode cell surface proteins and due to their subcellular localization these proteins represent excellent targets for cancer diagnosis and therapeutics. Therefore, a precise characterization of the surfaceome set in different types of tumor is needed. Using TCGA data from 15 different tumor types and a new method to identify cancer genes, the -score, we identified several potential therapeutic targets within the surfaceome set. This allowed us to expand a previous analysis from us and provided a clear characterization of the human surfaceome in the tumor landscape. Moreover, we present evidence that a three-gene set—WNT5A, CNGA2, and IGSF9B—can be used as a signature associated with shorter survival in breast cancer patients. The data made available here will help the community to develop more efficient diagnostic and therapeutic tools for a variety of tumor types
Bioinformatics Analysis of the Human Surfaceome Reveals New Targets for a Variety of Tumor Types
(2016-10-18) Fonseca, André L.; Silva, Vandeclécio L. da; Fonseca, Marbella M.; Meira, Isabella T. J.; Silva, Thayná E. da; Kroll, José Eduardo; Ribeiro-dos-Santos, André M.; Freitas, Cléber R.; Furtado, Raimundo; Souza, Sandro José de; Ferreira, Beatriz Stransky; Souza, Sandro José de
It is estimated that 10 to 20% of all genes in the human genome encode cell surface proteins and due to their subcellular localization these proteins represent excellent targets for cancer diagnosis and therapeutics. Therefore, a precise characterization of the surfaceome set in different types of tumor is needed. Using TCGA data from 15 different tumor types and a new method to identify cancer genes, the -score, we identified several potential therapeutic targets within the surfaceome set. This allowed us to expand a previous analysis from us and provided a clear characterization of the human surfaceome in the tumor landscape. Moreover, we present evidence that a three-gene set—WNT5A, CNGA2, and IGSF9B—can be used as a signature associated with shorter survival in breast cancer patients. The data made available here will help the community to develop more efficient diagnostic and therapeutic tools for a variety of tumor types.
Comparação entre amostras selvagem e BRCA-associadas em câncer de ovário
(Universidade Federal do Rio Grande do Norte, 2016-12-01) Coêlho, Ana Carolina Miranda Fernandes; Souza, Jorge Estefano Santana de; Kroll, José Eduardo
O câncer de ovário representa a principal causa de morte dentre as neoplasias malignas ginecológicas. Apesar da evolução das técnicas cirúrgicas e dos regimes quimioterápicos, a taxa de sobrevida das pacientes com câncer de ovário continua baixa devido ao diagnóstico tardio. Mutações nos genes BRCA constituem o fator de risco mais significativo para o desenvolvimento dessa doença. Usando dados do TCGA, para esta neoplasia específica, juntamente com o método do S-score, foram identificados genes previamente conhecidos e de outros potencias genes envolvidos no processo de carcinogênese. Além disso, propôs-se assinaturas gênicas, compostas por três genes, associadas à uma sobrevida mais curta em pacientes com câncer de ovário. Portanto, os dados apresentados nesse estudo poderão auxiliar o desenvolvimento de ferramentas diagnósticas e terapêuticas mais eficientes, baseadas nas características moleculares do tumor, possibilitando uma redução na taxa de mortalidade associada ao câncer de ovário.
dbPepVar: A novel cancer proteogenomics database
(Institute of Electrical and Electronics Engineers (IEEE), 2022-08) Cunha, Lucas Marques da; Terrematte, Patrick Cesar Alves; Fiúza, Tayná da Silva; Silva, Vandeclecio Lira da; Kroll, José Eduardo; Souza, Sandro José de; Souza, Gustavo Antonio de
Cancers arise from the acquisition of DNA mutations, such as substitutions, deletions, amplifications, and rearrangements. Understanding the distribution and correlation of such mutations in cancer may aid the characterization of the disease and subsequent identification of biomarkers for diagnosis and treatment. The proteogenomics database (dbPepVar) created here combines genetic variation information from dbSNP with protein sequences from NCBI’s RefSeq. Public mass spectrometry datasets (Ovarian, Colorectal, Breast, and Prostate) were used to perform a pan-cancer analysis, allowing the identification of unique genetic variations. As a result, 3,726 variant peptides were identified in samples from patients with ovarian cancer, 2,543 in prostate, 2,661 in breast and 2,411 in colon-rectal cancer patients. Data resulting from the proteogenomics approach employed and connected to other biological databases is now available in an intuitive and dynamic web portal where novice users can explore general aspects of the dataset in graph or table format, or dive in to filter the data with click and select options or using more advanced queries with regex. All data can be downloaded in csv or pdf format. In perspective, the web portal developed may direct studies to identify new therapeutic targets for different cancers, and one can also use our database for characterization of variants in samples of unknown genetic background, such as archived samples
Genome-wide identification of cancer/testis genes and their association with prognosis in a pan-cancer analysis
(Impact Journals, 2017-10-10) Silva, Vandeclécio Lira da; Fonseca, André Faustino; Fonseca, Marbella M.; Silva, Thayna Emília da; Coelho, Ana Carolina; Kroll, José Eduardo; Souza, Jorge Estefano Santana de; Ferreira, Beatriz Stransky; Souza, Gustavo Antônio de; Souza, Sandro José de
Cancer/testis (CT) genes are excellent candidates for cancer immunotherapies because of their restrict expression in normal tissues and the capacity to elicit an immune response when expressed in tumor cells. In this study, we provide a genomewide screen for CT genes with the identification of 745 putative CT genes. Comparison with a set of known CT genes shows that 201 new CT genes were identified. Integration of gene expression and clinical data led us to identify dozens of CT genes associated with either good or poor prognosis. For the CT genes related to good prognosis, we show that there is a direct relationship between CT gene expression and a signal for CD8+ cells infiltration for some tumor types, especially melanoma
Identifcation of rare alternative splicing events in MS/MS data reveals a signifcant fraction of alternative translation initiation sites
(2014-11-13) Kroll, José Eduardo; Souza, Sandro José de; Souza, Gustavo A. de
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.
Identification of NUDT15 gene variants in Amazonian Amerindians and admixed individuals from northern Brazil
(2020-04-15) Rodrigues, Juliana Carla Gomes; Souza, Tatiane Piedade de; Pastana, Lucas Favacho; Santos, André Maurício Ribeiro dos; Fernandes, Marianne Rodrigues; Pinto, Pablo; Wanderley, Alayde Vieira; Souza, Sandro José de; Kroll, José Eduardo; Pereira, Adenilson Leão; Magalhães, Leandro; Mercês, Laís Reis das; Vidal, Amanda Ferreira; Vinasco-Sandoval, Tatiana; Cavalcante, Giovanna Chaves; Guerreiro, João Farias; Assumpção, Paulo Pimentel de; Ribeiro-dos-Santos, Ândrea; Santos, Sidney; Santos, Ney Pereira Carneiro dos
Introduction The nudix hydrolase 15 (NUDT15) gene acts in the metabolism of thiopurine, by catabolizing its active metabolite thioguanosine triphosphate into its inactivated form, thioguanosine monophosphate. The frequency of alternative NUDT15 alleles, in particular those that cause a drastic loss of gene function, varies widely among geographically distinct populations. In the general population of northern Brazilian, high toxicity rates (65%) have been recorded in patients treated with the standard protocol for acute lymphoblastic leukemia, which involves thiopurine-based drugs. The present study characterized the molecular profile of the coding region of the NUDT15 gene in two groups, non-admixed Amerindians and admixed individuals from the Amazon region of northern Brazil. Methods The entire NUDT15 gene was sequenced in 64 Amerindians from 12 Amazonian groups and 82 admixed individuals from northern Brazil. The DNA was extracted using phenol-chloroform. The exome libraries were prepared using the Nextera Rapid Capture Exome (Illumina) and SureSelect Human All Exon V6 (Agilent) kits. The allelic variants were annotated in the ViVa® (Viewer of Variants) software. Results Four NUDT15 variants were identified: rs374594155, rs1272632214, rs147390019, andrs116855232. The variants rs1272632214 and rs116855232 were in complete linkage disequilibrium, and were assigned to the NUDT15*2 genotype. These variants had high frequencies in both our study populations in comparison with other populations catalogued in the 1000 Genomes database. We also identified the NUDT15*4 haplotype in our study populations, at frequencies similar to those reported in other populations from around the world. Conclusion Our findings indicate that Amerindian and admixed populations from northern Brazil have high frequencies of the NUDT15 haplotypes that alter the metabolism profile of thiopurines.
Identification of variants (rs11571707, rs144848, and rs11571769) in the BRCA2 gene associated with hereditary breast cancer in indigenous populations of the brazilian Amazon
(MDPI AG, 2021-01-22) Dobbin, Elizabeth Ayres Fragoso; Medeiros, Jéssyca Amanda Gomes; Costa, Marta Solange Camarinha Ramos; Rodrigues, Juliana Carla Gomes; Guerreiro, João Farias; Kroll, José Eduardo; Souza, Sandro José de; Assumpção, Paulo Pimentel de; Ribeiro-dos-Santos, Ândrea; Santos, Sidney Emanuel Batista dos; Burbano, Rommel Mario Rodríguez; Fernandes, Marianne Rodrigues; Santos, Ney Pereira Carneiro dos
Estimates show that 5–10% of breast cancer cases are hereditary, caused by genetic variants in autosomal dominant genes; of these, 16% are due to germline mutations in the BRCA1 and BRCA2 genes. The comprehension of the mutation profile of these genes in the Brazilian population, particularly in Amazonian Amerindian groups, is scarce. We investigated fifteen polymorphisms in the BRCA1 and BRCA2 genes in Amazonian Amerindians and compared the results with the findings of global populations publicly available in the 1000 Genomes Project database. Our study shows that three variants (rs11571769, rs144848, and rs11571707) of the BRCA2 gene, commonly associated with hereditary breast cancer, had a significantly higher allele frequency in the Amazonian Amerindian individuals in comparison with the African, American, European, and Asian groups analyzed. These data outline the singular genetic profiles of the indigenous population from the Brazilian Amazon region. The knowledge about BRCA1 and BRCA2 variants is critical to establish public policies for hereditary breast cancer screening in Amerindian groups and populations admixed with them, such as the Brazilian population
NFAT1 Transcription Factor Regulates Cell Cycle Progression and Cyclin E Expression in B Lymphocytes
(2016) Teixeira, Leonardo K.; Carrossini, Nina; Sécca, Cristiane; Kroll, José Eduardo; DaCunha, Déborah C.; Faget, Douglas V.; Carvalho, Lilian D. S.; Souza, Sandro José de; Viola, João P. B.
The NFAT family of transcription factors has been primarily related to T cell development, activation, and differentiation. Further studies have shown that these ubiquitous proteins are observed in many cell types inside and outside the immune system, and are involved in several biological processes, including tumor growth, angiogenesis, and invasiveness. However, the specific role of the NFAT1 family member in naive B cell proliferation remains elusive. Here, we demonstrate that NFAT1 transcription factor controls Cyclin E expression, cell proliferation, and tumor growth in vivo. Specifically, we show that inducible expression of NFAT1 inhibits cell cycle progression, reduces colony formation, and controls tumor growth in nude mice. We also demonstrate that NFAT1-deficient naive B lymphocytes show a hyperproliferative phenotype and high levels of Cyclin E1 and E2 upon BCR stimulation when compared to wild-type B lymphocytes. NFAT1 transcription factor directly regulates Cyclin E expression in B cells, inhibiting the G1/S cell cycle phase transition. Bioinformatics analysis indicates that low levels of NFAT1 correlate with high expression of Cyclin E1 in different human cancers, including Diffuse Large B-cell Lymphomas (DLBCL). Together, our results demonstrate a repressor role for NFAT1 in cell cycle progression and Cyclin E expression in B lymphocytes, and suggest a potential function for NFAT1 protein in B cell malignancies.
Splicing Express: a software suite for alternative splicing analysis using next-generation sequencing data
(2015-11-19) Kroll, José Eduardo; Kim, Jihoon; Ohno-Machado, Lucila; Souza, Sandro José de
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 from the Illumina Human Body Map and the Rat Body Map, we show that Splicing Express is able to perform all 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.
SPLOOCE: A new portal for the analysis of human splicing variants
(2012-11) Kroll, José Eduardo; Galante, Pedro A. F.; Ohara, Daniel T.; Navarro, Fábio C. P.; Ohno-Machado, Lucila; Souza, Sandro José de
Understanding alternative splicing is crucial to elucidate the mechanisms behind several biological phenomena, including diseases. The huge amount of expressed sequences available nowadays represents an opportunity and a challenge to catalog and display alternative splicing events (ASEs). Although several groups have faced this challenge with relative success, we still lack a computational tool that uses a simple and straightforward method to retrieve, name and present ASEs. Here we present SPLOOCE , a portal for the analysis of human splicing variants. SPLOOCE uses a method based on regular expressions for retrieval of ASEs. We propose a simple syntax that is able to capture the complexity of ASEs.
The genomic profile associated with risk of severe forms of COVID-19 in amazonian native american populations
(MDPI, 2022-04-01) Astana, Lucas Favacho; Silva, Thays Amâncio; Gellen, Laura Patrícia Albarello; Vieira, Giovana Miranda; Assunção, Letícia Almeida de; Leitão, Luciana Pereira Colares; Silva, Natasha Monte da; Coelho, Rita de Cássia Calderaro; Alcântara, Angélica Leite de; Vinagre, Lui Wallacy Morikawa Souza; Rodrigues, Juliana Carla Gomes; Leal, Diana Feio da Veiga Borges; Fernandes, Marianne Rodrigues Fernandes; Souza, Sandro José de; Kroll, José Eduardo; Santos, André Mauricio Riberio dos; Burbano, Rommel Mario Rodríguez Burbano; Guerreiro, João Farias; Assumpção, Paulo Pimentel de; Santos, Ândrea Campos Ribeiro dos; Santos, Sidney Emanuel Batista dos; Santos, Ney Pereira Carneiro dos.
Genetic factors associated with COVID-19 disease outcomes are poorly understood. This study aimed to associate genetic variants in the SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6, XCR1, and ABO genes with the risk of severe forms of COVID-19 in Amazonian Native Americans, and to compare the frequencies with continental populations. The study population was composed of 64 Amerindians from the Amazon region of northern Brazil. The difference in frequencies between the populations was analyzed using Fisher’s exact test, and the results were significant when p ≤ 0.05. We investigated 64 polymorphisms in 7 genes; we studied 47 genetic variants that were new or had impact predictions of high, moderate, or modifier. We identified 15 polymorphisms with moderate impact prediction in 4 genes (ABO, CXCR6, FYCO1, and SLC6A20). Among the variants analyzed, 18 showed significant differences in allele frequency in the NAM population when compared to others. We reported two new genetic variants with modifier impact in the Amazonian population that could be studied to validate the possible associations with COVID-19 outcomes. The genomic profile of Amazonian Native Americans may be associated with protection from severe forms of COVID-19. This work provides genomic data that may help forthcoming studies to improve COVID-19 outcomes
A tool for integrating genetic and mass spectrometry-based peptide data: proteogenomics viewer: PV: a genome browser-like tool, which includes MS data visualization and peptide identification parameters
(Wiley, 2017-07) Kroll, José Eduardo; Silva, Vandeclecio Lira da; Souza, Sandro José de; Souza, Gustavo Antonio de
In this manuscript we describe Proteogenomics Viewer, a web-based tool that collects MS peptide identification, indexes to genomic sequence and structure, assigns exon usage, reports the identified protein isoforms with genomic alignments and, most importantly, allows the inspection of MS2 information for proper peptide identification. It also provides all performed indexing to facilitate global analysis of the data. The relevance of such tool is that there has been an increase in the number of proteogenomic efforts to improve the annotation of both genomics and proteomics data, culminating with the release of the two human proteome drafts. It is now clear that mass spectrometry-based peptide identification of uncharacterized sequences, such as those resulting from unpredicted exon joints or non-coding regions, is still prone to a higher than expected false discovery rate. Therefore, proper visualization of the raw data and the corresponding genome alignments are fundamental for further data validation and interpretation.

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Navegando por Autor "Kroll, José Eduardo"