RRE: a tool for the extraction of non-coding regions surrounding annotated genes from genomic datasets

Abstract Summary: RRE allows the extraction of non-coding regions surrounding a coding sequence [i.e. gene upstream region, 5′-untranslated region (5′-UTR), introns, 3′-UTR, downstream region] from annotated genomic datasets available at NCBI. Availability: RRE parser and web-based interface are accessible at http://www.bioinformatica.unito.it/bioinformatics/rre/rre.htm

State of art fusion-finder algorithms are suitable to detect transcription-induced chimeras in normal tissues?

BACKGROUND: RNA-seq has the potential to discover genes created by chromosomal rearrangements. Fusion genes, also known as "chimeras", are formed by the breakage and re-joining of two different chromosomes. It is known that chimeras have been implicated in the development of cancer. Few publications in the past showed the presence of fusion events also in normal tissue, but with very limited overlaps between their results. More recently, two fusion genes in normal tissues were detected using both RNA-seq and protein data. Due to heterogeneous results in identifying chimeras in normal tissue, we decided to evaluate the efficacy of state of the art fusion finders in detecting chimeras in RNA-seq data from normal tissues. RESULTS: We compared the performance of six fusion-finder tools: FusionHunter, FusionMap, FusionFinder, MapSplice, deFuse and TopHat-fusion. To evaluate the sensitivity we used a synthetic dataset of fusion-products, called positive dataset; in these experiments FusionMap, FusionFinder, MapSplice, and TopHat-fusion are able to detect more than 78% of fusion genes. All tools were error prone with high variability among the tools, identifying some fusion genes not present in the synthetic dataset. To better investigate the false discovery chimera detection rate, synthetic datasets free of fusion-products, called negative datasets, were used. The negative datasets have different read lengths and quality scores, which allow detecting dependency of the tools on both these features. FusionMap, FusionFinder, mapSplice, deFuse and TopHat-fusion were error-prone. Only FusionHunter results were free of false positive. FusionMap gave the best compromise in terms of specificity in the negative dataset and of sensitivity in the positive dataset. CONCLUSIONS: We have observed a dependency of the tools on read length, quality score and on the number of reads supporting each chimera. Thus, it is important to carefully select the software on the basis of the structure of the RNA-seq data under analysis. Furthermore, the sensitivity of chimera detection tools does not seem to be sufficient to provide results consistent with those obtained in normal tissues on the basis of fusion events extracted from published data

Human papillomavirus infection in Rwanda at the moment of implementation of a national HPV vaccination programme

Background: Cervical cancer is the most common female cancer in Rwanda that, in 2011, became the first African country to implement a national vaccination programme against human papillomavirus (HPV). Methods: To provide a robust baseline for future evaluations of vaccine effectiveness, cervical cell specimens were obtained from 2508 women aged 18–69 years from the general population in Kigali, Rwanda, during 2013/14. 20 % of women were HIV-positive. Samples were used for liquid-based cytology and HPV testing (44 types) with GP5+/6+ PCR. Results: HPV prevalence was 34 %, being highest (54 %) in women ≤19 years and decreasing to 20 % at age ≥50. Prevalence of high risk (HR) HPV and cytological abnormalities was 22 and 11 % respectively (including 2 % with high-grade squamous intraepithelial lesions, HSIL) decreasing with age. Age-standardised prevalence of HR HPV was 22 % (or 19 % among HIV-negative women), and HPV16 was the most common type. Prevalence of HPV and cytological abnormalities were significantly higher in HIV-positive than HIV-negative women, and the difference increased with age. Other significant risk factors for HPV positivity in multivariate analyses were high lifetime number of sexual partners, receiving cash for sex, and being a farmer. 40 % of women with HSIL were infected with HPV16/18 and there was no significant difference between HIV-positive and HIV-negative women. Conclusions: This study confirms Rwanda to be a setting of high prevalence of HPV and cervical disease that is worsened by HIV. These data will serve as a robust baseline for future evaluations of HPV vaccine programme effectiveness

Dynamic Models for Public Health

Dynamic models are important tools for public health purposes; they allow esimaing the impact of diferent approaches and can be used for a populaion health improvement planning or to organize a response to an emerging public health issue. The aims of my thesis are to design, build, test, parameterized, and illustrated two dynamic models. One is a populaion-based model of Human Papilloma Virus (HPV) infecion natural history and vaccinaion; the other is an individual based model of tobacco control. Both models have been adapted to account for public health measure of prevenion and control. Also, both models can incorporate enough demographic data to adapt their outputs to speciic populaion, in which realisic intervenions are simulated. The model of HPV transmission and control has been adapted and parameterized to represent diferent populaions from both high- and low-middle-income countries, i.e. Sweden, Italy, US, and India, and diferent HPV types, i.e. 16,18, and 45. By contrast, the model of tobacco control has been designed to reproduce smoking behaviors and demography of the Italian populaion between year 2000 and 2013 and used to evaluate the efect of public health policy, e.g. smoking prevalence on the Italian populaion in year 2030. Both models are coded in C compuing language, according to high-performance programming standards, eicient data structures and algorithms, and opimizaion techniques to maximize the compuing eiciency. In my thesis, I have used the two models to predict the expected impact of selected public health intervenions both for HPV and cervical cancer control and for tobacco control. The outputs of each set of simulations have been analysed using advanced staisical methods/libraries, e.g. GNU Scieniic Library and sotware such as R (CRAN) and STATA. These predicions illustrate the potenial of using mathemaical model for assessing the efeciveness of selected prevenion and control measures

Human Papillomavirus Vaccination at a Time of Changing Sexual Behavior

Human papillomavirus (HPV) prevalence varies widely worldwide. We used a transmission model to show links between age-specific sexual patterns and HPV vaccination effectiveness. We considered rural India and the United States as examples of 2 heterosexual populations with traditional age-specific sexual behavior and gender-similar age-specific sexual behavior, respectively. We simulated these populations by using age-specific rates of sexual activity and age differences between sexual partners and found that transitions from traditional to gender-similar sexual behavior in women <35 years of age can result in increased (2.6-fold in our study) HPV16 prevalence. Our model shows that reductions in HPV16 prevalence are larger if vaccination occurs in populations before transitions in sexual behavior and that increased risk for HPV infection attributable to transition is preventable by early vaccination. Our study highlights the importance of using time-limited opportunities to introduce HPV vaccination in traditional populations before changes in age-specific sexual patterns occur