Mining for viral fragments in methylation enriched sequencing data

Most next generation sequencing experiments generate more data than is required for the experimental set up. For example, methyl-CpG binding domain (MBD) affinity purification based sequencing is often used for DNA-methylation profiling, but up to 30% of the sequenced fragments cannot be mapped uniquely to the reference genome. Here we present and evaluate a methodology for the identification of viruses in these otherwise unused paired-end MBD-seq data. Viral detection is accomplished by mapping non-reference alignable reads to a comprehensive set of viral genomes. As viruses play an important role in epigenetics and cancer development, 92 (pre)malignant and benign samples, originating from two different collections of cervical samples and related cell lines, were used in this study. These samples include primary carcinomas (n=22), low- & high-grade cervical intrapeithelial neoplasia (CIN1 & CIN2/3 - n=2/n=30) and normal tissue (n=20), as well as control samples (n=17). Viruses that were detected include phages, adenoviruses, herpesviridae and HPV. HPV, which causes virtually all cervical cancers, was identified in 95% of the carcinomas, 100% of the CIN2/3 samples, both CIN1 samples and in 55% of the normal samples. Comparing the amount of mapped fragments on HPV for each HPV-infected sample yielded a significant difference between normal samples and carcinomas or CIN2/3 samples (adjusted p-values resp. < 10^-5, < 10^-5), reflecting different viral loads and/or methylation degrees in non-normal samples. Fragments originating from different HPV types could be distinguished and were independently validated by PCR-based assays with a specificity of 98% and a sensitivitity of 66%. In conclusion, although limited by the a priori knowledge of viral reference genome sequences, the proposed methodology can provide a first but substantial insight into the presence, concentration and types of methylated viral sequences in MBD-seq data without additional costs

Should You Hire [email protected]?

When a person applies for a job online, one of the first things a recruiter learns about the applicant is the applicant’s e-mail address. So what might a recruiter think about an applicant who refers to himself as DemonSeed420@ mail.com or [email protected]? That is, would job applicants with unprofessional e-mail addresses behave less professionally than applicants with more appropriate addresses? Will [email protected] be as unstable as she claims to be? Should an employer take a chance on [email protected]? Managers often make snap judgments about job candidates (Howard & Ferris, 1996) and do so using whatever information is available to them including the candidate’s smile, clothing, handshake, small talk (Barrick, Swider & Stewart, 2010), or name. For instance, Bertrand and Mullainathan (2004) mailed resumés in response to help wanted advertisements in Boston and Chicago. The researchers mailed identical resumés, manipulating only the first name of the applicants to be either a stereotypically “White” name or a stereotypically “African-American” name. Across all industries, occupations, and employer sizes, resumés with “White” names (e.g., Greg, Brad, Kristen, and Allison) received 50% more callbacks than did resumes with “African-American” names (e.g., Darnell, Jermaine, Latoya, and Tanisha). E-mail addresses function like names but e-mail addresses may have a greater potential to shape impressions than a given and/or family name because they can reflect more than gender and ethnicity. For example, e-mail addresses can imply skills ([email protected]), political affiliation (BlueDem@ mail.com), interests ([email protected]), and values ([email protected]). In a study about the relationship between e-mail addresses and personality traits, Back, Schmukle, and Egloff (2008) asked 600 university students to complete the Big Five Inventory. The researchers then gave the students’ e-mail addresses to a group of judges and asked the judges to guess how each student would score on the Big Five. The authors found that the judges were able to guess how the students scored on Openness and Conscientiousness. For example, judges guessed that students with addresses like [email protected] and [email protected] would score low on Conscientiousness, and they were right. Like Back and her colleagues, we tested the relationship between e-mail address and personality, but we also wanted to know if an address could tell us something about an applicant’s job qualifications. More specifically, we asked if candidates with addresses that contained references to sex, antisocial behavior, and deviant interests were less intelligent, conscientious, professional, and experienced than applicants without these types of references. We also asked if candidates with nondeviant but otherwise nonprofessional addresses including cutesy, geeky, and immature addresses were less qualified than candidates with more professional addresses