Embedding of Genes Using Cancer Gene Expression Data: Biological Relevance and Potential Application on Biomarker Discovery

Artificial neural networks (ANNs) have been utilized for classification and prediction task with remarkable accuracy. However, its implications for unsupervised data mining using molecular data is under-explored. We found that embedding can extract biologically relevant information from The Cancer Genome Atlas (TCGA) gene expression dataset by learning a vector representation through gene co-occurrence. Ground truth relationship, such as cancer types of the input sample and semantic meaning of genes, were showed to retain in the resulting entity matrices. We also demonstrated the interpretability and usage of these matrices in shortlisting candidates from a long gene list as in the case of immunotherapy response. 73 related genes are singled out while the relatedness of 55 genes with immune checkpoint proteins (PD-1, PD-L1, and CTLA-4) are supported by literature. 16 novel genes (ACAP1, C11orf45, CD79B, CFP, CLIC2, CMPK2, CXCR2P1, CYTIP, FER, MCTO1, MMP25, RASGEF1B, SLFN12, TBC1D10C, TRAF3IP3, TTC39B) related to immune checkpoint proteins were identified. Thus, this method is feasible to mine big volume of biological data, and embedding would be a valuable tool to discover novel knowledge from omics data. The resulting embedding matrices mined from TCGA gene expression data are interactively explorable online (http://bit.ly/tcga-embedding-cancer) and could serve as an informative reference for gene relatedness in the context of cancer and is readily applicable to biomarker discovery of any molecular targeted therapy

A Parametric Study of an Effective Stress Liquefaction Model

A method for evaluating the soil parameters required for effective stress analyses of the earthquake liquefaction potential of saturated sands is described. By means of parametric studies, it is demonstrated that the drained volume change and rebound constants required, may be backfitted to match a given field liquefaction strength curve. By means of this technique, fully coupled effective stress response analyses and site liquefaction evaluations can become a more routine engineering tool

Fios e desafios da atenção à saúde da criança no estado do Espírito Santo: análise da mortalidade de zero a cinco anos com gestores do Programa Estadual de Saúde da Mulher e da Criança

Trata-se de um estudo de abordagem qualitativa que objetivou discutir a mortalidade de zero a cinco anos, no estado do Espírito Santo, no lapso de agosto de 2011 a agosto de 2012, a partir de matérias veiculadas por um jornal diário da mídia impressa de grande circulação, a saber A Gazeta. As referidas matérias constituíram uma hemeroteca que subsidiou a criação de um painel reprográfico. Os sujeitos da investigação foram os técnicos que compõem a equipe da Coordenação do Programa Estadual de Saúde da Mulher e da Criança, e a produção do material de estudo se deu a partir da análise de um grupo focal, com roteiro semiestruturado, tendo como partida a análise de uma cópia do painel contendo todas as máterias. Todo o material foi gravado e filmado. A Análise Institutucional foi a baliza norteadora de toda a elaboração e descrição do estudo. Conforme preconiza este quadro teórico proposto por Lourau, a etapa final do projeto constituiu-se em uma restituição concreta parte do procedimento científico, tratando-se da discussão das produções na pesquisa com os interessados, de modo a possibilitar a sua interferência direta neste processo. O estudo demonstrou que os sujeitos, a partir do dispositivo analisador natural, a morte de crianças menores de cinco anos, conseguiram fazer uma reflexão sobre o quanto é necessário buscar uma interlocução com os demais setores e perceber que a análise institucional, com sua potência de provocar a autoanálise e a autogestão, proporcionou-lhes uma possibilidade de repensar seus processos de trabalho na atenção à saúde da criança

Social Europe. No 2/87

BACKGROUND: DNA methylation is an important type of epigenetic modification involved in gene regulation. Although strong DNA methylation at promoters is widely recognized to be associated with transcriptional repression, many aspects of DNA methylation remain not fully understood, including the quantitative relationships between DNA methylation and expression levels, and the individual roles of promoter and gene body methylation. RESULTS: Here we present an integrated analysis of whole-genome bisulfite sequencing and RNA sequencing data from human samples and cell lines. We find that while promoter methylation inversely correlates with gene expression as generally observed, the repressive effect is clear only on genes with a very high DNA methylation level. By means of statistical modeling, we find that DNA methylation is indicative of the expression class of a gene in general, but gene body methylation is a better indicator than promoter methylation. These findings are general in that a model constructed from a sample or cell line could accurately fit the unseen data from another. We further find that promoter and gene body methylation have minimal redundancy, and either one is sufficient to signify low expression. Finally, we obtain increased modeling power by integrating histone modification data with the DNA methylation data, showing that neither type of information fully subsumes the other. CONCLUSION: Our results suggest that DNA methylation outside promoters also plays critical roles in gene regulation. Future studies on gene regulatory mechanisms and disease-associated differential methylation should pay more attention to DNA methylation at gene bodies and other non-promoter regions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-014-0408-0) contains supplementary material, which is available to authorized users

Genomic and protein expression analysis reveals flap endonuclease 1 (FEN1) as a key biomarker in breast and ovarian cancer

FEN1 has key roles in Okazaki fragment maturation during replication, long patch base excision repair, rescue of stalled replication forks, maintenance of telomere stability and apoptosis. FEN1 may be dysregulated in breast and ovarian cancers and have clinicopathological significance in patients. We comprehensively investigated FEN1 mRNA expression in multiple cohorts of breast cancer [training set (128), test set (249), external validation (1952)]. FEN1 protein expression was evaluated in 568 oestrogen receptor (ER) negative breast cancers, 894 ER positive breast cancers and 156 ovarian epithelial cancers. FEN1 mRNA overexpression was highly significantly associated with high grade (p= 4.89 x 10 - 57) , high mitotic index (p= 5.25 x 10 - 28), pleomorphism (p= 6.31 x 10-19), ER negative (p= 9.02 x 10-35 ), PR negative (p= 9.24 x 10-24 ), triple negative phenotype (p= 6.67 x 10-21) , PAM50.Her2 (p=5.19 x 10-13 ), PAM50.Basal (p=2.7 x 10-41), PAM50.LumB (p=1.56 x 10-26), integrative molecular cluster 1 (intClust.1) ( p=7.47 x 10-12), intClust.5 (p=4.05 x 10-12) and intClust. 10 (p=7.59 x 10-38 ) breast cancers. FEN1 mRNA overexpression is associated with poor breast cancer specific survival in univariate (p=4.4 x 10-16) and multivariate analysis (p=9.19 x 10-7). At the protein level, in ER positive tumours , FEN1 overexpression remains significantly linked to high grade, high mitotic index and pleomorphism (ps< 0.01). In ER negative tumours, high FEN1 is significantly associated with pleomorphism, tumour type, lymphovascular invasion, triple negative phenotype, EGFR and HER2 expression (ps<0.05). In ER positive as well as in ER negative tumours, FEN1 protein over expression is associated with poor survival in univariate and multivariate analysis (ps<0.01). In ovarian epithelial cancers , similarly, FEN1 overexpression is associated with high grade, high stage and poor survival (ps<0.05). We conclude that FEN1 is a promising biomarker in breast and ovarian epithelial cancer

Editorial

info:eu-repo/semantics/publishedVersio

Albumin-bilirubin grade predicts the outcomes of liver resection versus radiofrequency ablation for very early/early stage of hepatocellular carcinoma

Background and purposeWhether liver resection or ablation should be the first-line treatment for very early/early hepatocellular carcinoma (HCC) in patients who are candidates for both remains controversial. The aim of this study was to determine if the newly-developed Albumin-Bilirubin (ALBI) grade might help in treatment selections and to evaluate the survival of patients treated with liver resection and radiofrequency ablation (RFA).MethodsPatients with BCLC stage 0/A HCC who were treated with curative liver resection and RFA from 2003 to 2013 were included. Baseline clinical and laboratory parameters were retrieved and reviewed from the hospital database. Liver function and its impact on survival was assessed by the ALBI score. Overall and disease-free survivals were compared between the two groups.Results488 patients underwent liver resection (n = 318) and RFA (n = 170) for BCLC stage 0/A HCC during the study period. Liver resection offered superior survival to RFA in patients with BCLC stage 0/A HCC in the whole cohort. After propensity score matching, liver resection offered superior overall survival and disease-free survival to RFA in patients with ALBI grade 1 (P = 0.0002 and P ConclusionsLiver resection offered superior survival to RFA in patients with BCLC stage 0/A HCC. The ALBI grade could identify those patients with worse liver function who did not gain any survival advantage from curative liver resection

Electronic cigarette use was not associated with quitting of conventional cigarettes in youth smokers

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