Biochemical pathways analysis of microarray results: regulation of myogenesis in pigs

<p>Abstract</p> <p>Background</p> <p>Combining microarray results and biological pathway information will add insight into biological processes. Pathway information is widely available in databases through the internet.</p> <p>Mammalian muscle formation has been previously studied using microarray technology in pigs because these animals are an interesting animal model for muscle formation due to selection for increased muscle mass. Results indicated regulation of the expression of genes involved in proliferation and differentiation of myoblasts, and energy metabolism. The aim of the present study was to analyse microarrays studying myogenesis in pigs. It was necessary to develop methods to search biochemical pathways databases.</p> <p>Results</p> <p>PERL scripts were developed that used the names of the genes on the microarray to search databases. Synonyms of gene names were added to the list by searching the Gene Ontology database. The KEGG database was searched for pathway information using this updated gene list. The KEGG database returned 88 pathways. Most genes were found in a single pathway, but others were found in up to seven pathways. Combining the pathways and the microarray information 21 pathways showed sufficient information content for further analysis. These pathways were related to regulation of several steps in myogenesis and energy metabolism. Pathways regulating myoblast proliferation and muscle fibre formation were described. Furthermore, two networks of pathways describing the formation of the myoblast cytoskeleton and regulation of the energy metabolism during myogenesis were presented.</p> <p>Conclusion</p> <p>Combining microarray results and pathways information available through the internet provide biological insight in how the process of porcine myogenesis is regulated.</p

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Post-colonoscopy colorectal cancers in a national FIT-based CRC screening program

Background and study aims: Post-colonoscopy colorectal cancers (PCCRCs) decrease the effect of colorectal cancer (CRC) screening programs. To enable PCCRC incidence reduction on the long-term we classified PCCRCs diagnosed after colonoscopies performed in a fecal immunochemical test (FIT-) based screening program. Patients and methods: PCCRCs diagnosed after colonoscopies performed between 2014-2016 for positive FIT in the Dutch CRC screening program were included. PCCRCs were categorized according to the World Endoscopy Organization consensus statement into a) interval PCCRC (diagnosed before the recommended surveillance), b) non-interval-type-A (diagnosed at the recommended surveillance interval), c) non-interval-type-B (diagnosed after the recommended surveillance interval), or d) non-interval-type-C (diagnosed after the intended recommended surveillance interval, but not applied due to comorbidity). The most probable etiology was determined by root-cause analysis. Tumor stage distributions were compared between categories. Results: 116,362 colonoscopies were performed after positive FIT with 9,978 screen-detected CRCs. During follow-up, 432 PCCRCs were diagnosed. The 3-year PCCRC rate was 2.7%. PCCRCs were categorized as interval (53.5%), non-interval-type-A (14.6%), non-interval-type-B (30.6%), and non-interval-type-C (1.4%). Interval PCCRCs had as most common etiology a possible missed lesion with adequate examination (73.6%) and were more often diagnosed at an advanced stage (stage III/IV, 53.2%) compared to non-interval-type-A (15.9%, p&lt;0.001) and non-interval-type-B (40.9%, p=0.025) PCCRCs. Conclusions: The 3-year PCCRC rate was low in this FIT-based CRC screening program. Approximately half of PCCRCs were interval PCCRCs. These were mostly caused by missed lesions and were diagnosed at more advanced stage. This emphasizes the importance of high-quality colonoscopy with optimal polyp detection.</p

Colémbolos (Hexapoda) como bioindicadores de la calidad de suelos

Se evaluaron invertebrados del suelo, en particular los colémbolos, como bioindicadores de la calidad de suelos contaminados con hidrocarburos en el sureste de México. Se realizaron 2 muestreos en verano-otoño del 2004, en 4 parcelas de 2 hectáreas, denominadas zona 1, 2, 3 y control. De cada unidad se tomaron 8 muestras que fueron procesadas por medio del embudo de Berlese-Tullgren y 4 por el método de flotación. Para colémbolos se determinaron los siguientes índices ecológicos: abundancia, riqueza, índice de Shannon (H’), dominancia (λ), equidad(J’) e índice de similitud (S). Se realizaron análisis fi sicoquímicos del suelo: hidrocarburos totales del petróleo (HTP) e hidrocarburos aromáticos policíclicos (HAP), porosidad, pH, CE, MO, N, P, K, CIC y textura. Los HTP, en las zonas contaminadas, sobrepasan los límites de las normas mexicanas ambientales. En todas las zonas de estudio se observaron colémbolos, ácaros y larvas de dípteros, por lo que su abundancia y diversidad pueden ser utilizadas como bioindicadores del grado de contaminación y calidad del suelo. En las zonas contaminadas se registraron abundancias muy bajas de Crustacea, Formicidae, Araneae, Diptera, Pseudoscorpionida, y Diplopoda. Las familias de los colémbolos más ampliamente distribuidas fueron Sminthurididae e Isotomidae. De acuerdo con el análisis de correlación, su diversidad de colémbolos es afectada por la presencia de HAP (fl ouranteno, naftaleno, pireno, criseno y fenantreno)

Analysis of a simulated microarray dataset: Comparison of methods for data normalisation and detection of differential expression (Open Access publication)

Microarrays allow researchers to measure the expression of thousands of genes in a single experiment. Before statistical comparisons can be made, the data must be assessed for quality and normalisation procedures must be applied, of which many have been proposed. Methods of comparing the normalised data are also abundant, and no clear consensus has yet been reached. The purpose of this paper was to compare those methods used by the EADGENE network on a very noisy simulated data set. With the a priori knowledge of which genes are differentially expressed, it is possible to compare the success of each approach quantitatively. Use of an intensity-dependent normalisation procedure was common, as was correction for multiple testing. Most variety in performance resulted from differing approaches to data quality and the use of different statistical tests. Very few of the methods used any kind of background correction. A number of approaches achieved a success rate of 95% or above, with relatively small numbers of false positives and negatives. Applying stringent spot selection criteria and elimination of data did not improve the false positive rate and greatly increased the false negative rate. However, most approaches performed well, and it is encouraging that widely available techniques can achieve such good results on a very noisy data set

Six Months of Balloon Treatment does Not Predict the Success of Gastric Banding

BACKGROUND: We studied whether weight loss by intragastric balloon would predict the outcome of subsequent gastric banding with regard to weight loss and BMI reduction. METHODS: A prospective cohort of patients with a body mass index (BMI)>40 kg/m(2) received an intragastric balloon for 6 months followed by laparoscopic adjustable gastric banding (LAGB). Successful balloon-induced weight loss was defined as > or =10% weight loss after 6 months. Successful surgical weight loss was defined as an additional 15% weight loss in the following 12 months. Patients were divided in group A, losing > or =10% of their initial weight with 6 months' balloon treatment, and group B, losing <10% of their initial weight. RESULTS: In 40 patients (32 female, 8 male; age 36.6 yr, range 26-54), the mean BMI decreased from 46.5 to 40.5 kg/m(2) (P <0.001) after 6 months of balloon treatment and to 35.2 kg/m(2) (P <0.001) 12 months after LAGB. Group A (25 patients) and group B (15 patients) had a significant difference in BMI decrease, 12.4 vs 9.0 kg/m(2) (P <0.05), after the total study duration of 18 months. However, there was no difference in BMI reduction (4.7 kg/m(2) vs 5.8 kg/m(2)) in the 12 months after LAGB. 6 patients in group A lost > or =10% of their starting weight during 6 months balloon treatment as well as > or =15% 12 months following LAGB. 6 patients in group B lost <10% of their starting weight after 6 months of BIB, but also lost > or =15% 12 months following LAGB. CONCLUSION: Intragastric balloon did not predict the success of subsequent LAG