ViVar: A Comprehensive Platform for the Analysis and Visualization of Structural Genomic Variation

Structural genomic variations play an important role in human disease and phenotypic diversity. With the rise of high-throughput sequencing tools, mate-pair/paired-end/single-read sequencing has become an important technique for the detection and exploration of structural variation. Several analysis tools exist to handle different parts and aspects of such sequencing based structural variation analyses pipelines. A comprehensive analysis platform to handle all steps, from processing the sequencing data, to the discovery and visualization of structural variants, is missing. The ViVar platform is built to handle the discovery of structural variants, from Depth Of Coverage analysis, aberrant read pair clustering to split read analysis. ViVar provides you with powerful visualization options, enables easy reporting of results and better usability and data management. The platform facilitates the processing, analysis and visualization, of structural variation based on massive parallel sequencing data, enabling the rapid identification of disease loci or genes. ViVar allows you to scale your analysis with your work load over multiple (cloud) servers, has user access control to keep your data safe and is easy expandable as analysis techniques advance. URL: https://www.cmgg.be/vivar/     

Molecular Optical Simulation Environment (MOSE): A Platform for the Simulation of Light Propagation in Turbid Media

The study of light propagation in turbid media has attracted extensive attention in the field of biomedical optical molecular imaging. In this paper, we present a software platform for the simulation of light propagation in turbid media named the “Molecular Optical Simulation Environment (MOSE)”. Based on the gold standard of the Monte Carlo method, MOSE simulates light propagation both in tissues with complicated structures and through free-space. In particular, MOSE synthesizes realistic data for bioluminescence tomography (BLT), fluorescence molecular tomography (FMT), and diffuse optical tomography (DOT). The user-friendly interface and powerful visualization tools facilitate data analysis and system evaluation. As a major measure for resource sharing and reproducible research, MOSE aims to provide freeware for research and educational institutions, which can be downloaded at http://www.mosetm.net.     

BIRS – Bioterrorism Information Retrieval System

Bioterrorism is the intended use of pathogenic strains of microbes to widen terror in a population. There is a definite need to promote research for development of vaccines, therapeutics and diagnostic methods as a part of preparedness to any bioterror attack in the future. BIRS is an open-access database of collective information on the organisms related to bioterrorism. The architecture of database utilizes the current open-source technology viz PHP ver 5.3.19, MySQL and IIS server under windows platform for database designing. Database stores information on literature, generic- information and unique pathways of about 10 microorganisms involved in bioterrorism. This may serve as a collective repository to accelerate the drug discovery and vaccines designing process against such bioterrorist agents (microbes). The available data has been validated from various online resources and literature mining in order to provide the user with a comprehensive information system.

Availability

The database is freely available at http://www.bioterrorism.biowaves.org     

Should Informed Consent for Cancer Treatment Include a Discussion about Hospital Outcome Disparities?

Background to the debate: Several studies have found disparities in the outcome of medical procedures across different hospitals—better outcomes have been associated with higher procedure volume. An Institute of Medicine workshop found such a “volume–outcome relationship” for two types of cancer surgery: resection of the pancreas and esophagus (http://www.iom.edu/?id=31508). This debate examines whether physicians have an ethical obligation to inform patients of hospital outcome disparities for these cancers.     

Report on the 2nd Annual Infinium Humanmethylation450 Array Workshop

The Illumina Infinium HumanMethylation450 BeadChip – the successor to their hugely popular HumanMethylation27 BeadChip – is arguably the most prevalent platform for large-scale studies of DNA methylome analysis. After the success of last year’s meeting¹ that discussed initial analysis strategies for this then-new platform, this year’s meeting (held at Queen Mary, University of London) included the presentation of now established pipelines and normalization methods for data analysis, as well as some exciting tools for down-stream analysis. The importance of defining cell composition was a new topic mentioned by most speakers. The epigenome varies between cell types and insuring that methylation differences are related to sample treatment and not a differing cell population is essential. The meeting was attended by 215 computational and bench scientists from 18 countries. There were 11 speakers, a small poster session, and a discussion session. Talks were recorded and are now freely available at http://www.illumina.com/applications/epigenetics/array-based_methylation_analysis/methylation-array-analysis-education.ilmn     

Avanti lipid tools: Connecting lipids,technology, and cell biology

Lipid research is challenging owing to the complexity and diversity of the lipidome. Here we review a set of experimental tools developed for the seasoned lipid researcher, as well as, those who are new to the field of lipid research. Novel tools for probing protein–lipid interactions, applications for lipid binding antibodies, enhanced systems for the cellular delivery of lipids, improved visualization of lipid membranes using gold-labeled lipids, and advances in mass spectrometric analysis techniques will be discussed. Because lipid mediators are known to participate in a host of signal transduction and trafficking pathways within the cell, a comprehensive lipid toolbox that aids the science of lipidomics research is essential to better understand the molecular mechanisms of interactions between cellular components. This article is part of a Special Issue entitled Tools to study lipid functions.     

Insect Innate Immunity Database (IIID): An Annotation Tool for Identifying Immune Genes in Insect Genomes

The innate immune system is an ancient component of host defense. Since innate immunity pathways are well conserved throughout many eukaryotes, immune genes in model animals can be used to putatively identify homologous genes in newly sequenced genomes of non-model organisms. With the initiation of the “i5k” project, which aims to sequence 5,000 insect genomes by 2016, many novel insect genomes will soon become publicly available, yet few annotation resources are currently available for insects. Thus, we developed an online tool called the Insect Innate Immunity Database (IIID) to provide an open access resource for insect immunity and comparative biology research (http://www.vanderbilt.edu/IIID). The database provides users with simple exploratory tools to search the immune repertoires of five insect models (including Nasonia), spanning three orders, for specific immunity genes or genes within a particular immunity pathway. As a proof of principle, we used an initial database with only four insect models to annotate potential immune genes in the parasitoid wasp genus Nasonia. Results specify 306 putative immune genes in the genomes of N. vitripennis and its two sister species N. giraulti and N. longicornis. Of these genes, 146 were not found in previous annotations of Nasonia immunity genes. Combining these newly identified immune genes with those in previous annotations, Nasonia possess 489 putative immunity genes, the largest immune repertoire found in insects to date. While these computational predictions need to be complemented with functional studies, the IIID database can help initiate and augment annotations of the immune system in the plethora of insect genomes that will soon become available.     

Open Labware: 3-D Printing Your Own Lab Equipment

The introduction of affordable, consumer-oriented 3-D printers is a milestone in the current “maker movement,” which has been heralded as the next industrial revolution. Combined with free and open sharing of detailed design blueprints and accessible development tools, rapid prototypes of complex products can now be assembled in one’s own garage—a game-changer reminiscent of the early days of personal computing. At the same time, 3-D printing has also allowed the scientific and engineering community to build the “little things” that help a lab get up and running much faster and easier than ever before.Applications of 3-D printing technologies (Fig. 1A, Box 1) have become as diverse as the types of materials that can be used for printing. Replacement parts at the International Space Station may be printed in orbit from durable plastics or metals, while back on Earth the food industry is starting to explore the same basic technology to fold strings of chocolate into custom-shaped confectionary. Also, consumer-oriented laser-cutting technology makes it very easy to cut raw materials such as sheets of plywood, acrylic, or aluminum into complex shapes within seconds. The range of possibilities comes to light when those mechanical parts are combined with off-the-shelf electronics, low-cost microcontrollers like Arduino boards [1], and single-board computers such as a Beagleboard [2] or a Raspberry Pi [3]. After an initial investment of typically less than a thousand dollars (e.g., to set-up a 3-D printer), the only other materials needed to build virtually anything include a few hundred grams of plastic (approximately US$30/kg), cables, and basic electronic components [4,5].Open in a separate windowFig 1Examples of open 3-D printed laboratory tools. A ₁, Components for laboratory tools, such as the base for a micromanipulator [18] shown here, can be rapidly prototyped using 3-D printing. A _2, The printed parts can be easily combined with an off-the-shelf continuous rotation servo-motor (bottom) to motorize the main axis. B ₁, A 3-D printable micropipette [8], designed in OpenSCAD [19], shown in full (left) and cross-section (right). B ₂, The pipette consists of the printed parts (blue), two biro fillings with the spring, an off-the-shelf piece of tubing to fit the tip, and one screw used as a spacer. B ₃, Assembly is complete with a laboratory glove or balloon spanned between the two main printed parts and sealed with tape to create an airtight bottom chamber continuous with the pipette tip. Accuracy is ±2–10 μl depending on printer precision, and total capacity of the system is easily adjusted using two variables listed in the source code, or accessed via the “Customizer” plugin on the thingiverse link [8]. See also the first table.

Box 1. Glossary

Open source

A collective license that defines terms of free availability and redistribution of published source material. Terms include free and unrestricted distribution, as well as full access to source code/blueprints/circuit board designs and derived works. For details, see http://opensource.org.

Maker movement

Technology-oriented extension of the traditional “Do-it-Yourself (DIY)” movement, typically denoting specific pursuits in electronics, CNC (computer numerical control) tools such as mills and laser cutters, as well as 3-D printing and related technologies.

3-D printing

Technology to generate three-dimensional objects from raw materials based on computer models. Most consumer-oriented 3-D printers print in plastic by locally melting a strand of raw material at the tip (“hot-end”) and “drawing” a 3-D object in layers. Plastic materials include Acrylnitrile butadiene styrene (ABS) and Polylactic acid (PLA). Many variations of 3-D printers exist, including those based on laser-polymerization or fusion of resins or powdered raw materials (e.g., metal or ceramic printers).

Arduino boards

Inexpensive and consumer-oriented microcontroller boards built around simple processors. These boards offer a variety of interfaces (serial ports, I2C and CAN bus, etc.), μs-timers, and multiple general-purpose input-output (GPIO) pins suitable for running simple, time-precise programs to control custom-built electronics.

Single board computers

Inexpensive single-board computers capable of running a mature operating system with graphical-user interface, such as Linux. Like microcontroller boards, they offer a variety of hardware interfaces and GPIO pins to control custom-built electronics.It therefore comes as no surprise that these technologies are also routinely used by research scientists and, especially, educators aiming to customize existing lab equipment or even build sophisticated lab equipment from scratch for a mere fraction of what commercial alternatives cost [6]. Designs for such “Open Labware” include simple mechanical adaptors [7], micropipettes (Fig. 1B) [8], and an egg-whisk–based centrifuge [9] as well as more sophisticated equipment such as an extracellular amplifier for neurophysiological experiments [10], a thermocycler for PCR [11], or a two-photon microscope [12]. At the same time, conceptually related approaches are also being pursued in chemistry [13–15] and material sciences [16,17]. See also

Consent to ‘personal’ genomics and privacy

Direct-to-consumer genetic tests and population genome research challenge traditional notions of privacy and consentThe concerns about genetic privacy in the 1990s were largely triggered by the Human Genome Project (HGP) and the establishment of population biobanks in the following decade. Citizens and lawmakers were worried that genetic information on people, or even subpopulations, could be used to discriminate or stigmatize. The ensuing debates led to legislation both in Europe and the USA to protect the privacy of genetic information and prohibit genetic discrimination.Notions of genetic determinism have also been eroded as population genomics research has discovered a plethora of risk factors that offer only probabilistic value…Times have changed. The cost of DNA sequencing has decreased markedly, which means it will soon be possible to sequence individual human genomes for a few thousand dollars. Notions of genetic determinism have also been eroded as population genomics research has discovered a plethora of risk factors that offer only probabilistic value for predicting disease. Nevertheless, there are several increasingly popular internet genetic testing services that do offer predictions to consumers of their health risks on the basis of genetic factors, medical history and lifestyle. Also, not to be underestimated is the growing popularity of social networks on the internet that expose the decline in traditional notions of the privacy of personal information. It was only a matter of time until all these developments began to challenge the notion of genetic privacy.For instance, the internet-based Personal Genome Project asks volunteers to make their personal, medical and genetic information publicly available so as, “to advance our understanding of genetic and environmental contributions to human traits and to improve our ability to diagnose, treat, and prevent illness” (www.personalgenomes.org). The Project, which was founded by George Church at Harvard University, has enrolled its first 10 volunteers and plans to expand to 100,000. Its proponents have proclaimed the limitations, if not the death, of privacy (Lunshof et al, 2008) and maintain that, under the principle of veracity, their own personal genomes will be made public. Moreover, they have argued that in a socially networked world there can be no total guarantee of confidentiality. Indeed, total protection of privacy is increasingly unrealistic in an era in which direct-to-consumer (DTC) genetic testing is offered on the internet (Lee & Crawley, 2009) and forensic technologies can potentially ‘identify'' individuals in aggregated data sets, even if their identity has been anonymized (Homer et al, 2008).Since the start of the HGP in the 1990s, personal privacy and the confidentiality of genetic information have been important ethical and legal issues. Their ‘regulatory'' expression in policies and legislation has been influenced by both genetic determinism and exceptionalism. Paradoxically, there has been a concomitant emergence of collaborative and international consortia conducting genomics research on populations. These consortia openly share data, on the premise that it is for public benefit. These developments require a re-examination of an ‘ethics of scientific research'' that is founded solely on the protection and rights of the individual.… total protection of privacy is increasingly unrealistic in an era in which direct-to-consumer (DTC) genetic testing is offered on the internetAlthough personalized medicine empowers consumers and democratizes the sharing of ‘information'' beyond the data sharing that characterizes population genomics research (Kaye et al, 2009), it also creates new social groups based on beliefs of common genetic susceptibility and risk (Lee & Crawley, 2009). The increasing allure of DTC genetic tests and the growth of online communities based on these services also challenges research in population genomics to provide the necessary scientific knowledge (Yang et al, 2009). The scientific data from population studies might therefore lend some useful validation to the results from DTC, as opposed to the probabilistic ‘harmful'' information that is now provided to consumers (Ransohoff & Khoury, 2010; Action Group on Erosion, Technology and Concentration, 2008). Population data clearly erodes the linear, deterministic model of Mendelian inheritance, in addition to providing information on inherited risk factors. The socio-demographic data provided puts personal genetic risk factors in a ‘real environmental'' context (Knoppers, 2009).Thus, beginning with a brief overview of the principles of data sharing and privacy under both population and consumer testing, we will see that the notion of identifiability is closely linked to the definition of what constitutes ‘personal'' information. It is against this background that we need to examine the issue of consumer consent to online offers of genetic tests that promise whole-genome sequencing and analysis. Moreover, we also demonstrate the need to restructure ethical reviews of genetic research that are not part of classical clinical trials and that are non-interventionist, such as population studies.The HGP heralded a new open access approach under the Bermuda Principles of 1996: “It was agreed that all human genomic sequence information, generated by centres funded for large-scale human sequencing, should be freely available and in the public domain in order to encourage research and development and to maximise its benefit to society” (HUGO, 1996). Reaffirmed in 2003 under the Fort Lauderdale Rules, the premise was that, “the scientific community will best be served if the results of community resource projects are made immediately available for free and unrestricted use by the scientific community to engage in the full range of opportunities for creative science” (HUGO, 2003). The international Human Genome Organization (HUGO) played an important role in achieving this consensus. Its Ethics Committee considered genomic databases as “global public goods” (HUGO Ethics Committee, 2003). The value of this information—based on the donation of biological samples and health information—to realize the benefits of personal genomics is maximized through collaborative, high-quality research. Indeed, it could be argued that, “there is an ethical imperative to promote access and exchange of information, provided confidentiality is protected” (European Society of Human Genetics, 2003). This promotion of data sharing culminated in a recent policy on releasing research data, including pre-publication data (Toronto International Data Release Workshop, 2009).There is room for improvement in both the personal genome and the population genome endeavoursIn its 2009 Guidelines for Human Biobanks and Genetic Research Databases, the Organization for Economic Cooperation and Development (OECD) states that the “operators of the HBGRD [Human Biobanks and Genetic Research Databases] should strive to make data and materials widely available to researchers so as to advance knowledge and understanding.” More specifically, the Guidelines propose mechanisms to ensure the validity of access procedures and applications for access. In fact, they insist that access to human biological materials and data should be based on “objective and clearly articulated criteria [...] consistent with the participants'' informed consent”. Access policies should be fair, transparent and not inhibit research (OECD, 2009).In parallel to such open and public science was the rise of privacy protection, particularly when it concerns genetic information. The United Nations Educational, Scientific and Cultural Organization''s (UNESCO) 2003 International Declaration on Human Genetic Data (UNESCO, 2003) epitomizes this approach. Setting genetic information apart from other sensitive medical or personal information, it mandated an “express” consent for each research use of human genetic data or samples in the absence of domestic law, or, when such use “corresponds to an important public interest reason”. Currently, however, large population genomics infrastructures use a broad consent as befits both their longitudinal nature as well as their goal of serving future unspecified scientific research. The risk is that ethics review committees that require such continuous “express” consents will thereby foreclose efficient access to data in such population resources for disease-specific research. It is difficult for researchers to provide proof of such “important public interest[s]” in order to avoid reconsents.Personal information itself refers to identifying and identifiable information. Logically, a researcher who receives a coded data set but who does not have access to the linking keys, would not have access to ‘identifiable'' information and so the rules governing access to personal data would not apply (Interagency Advisory Panel on Research Ethics, 2009; OHRP, 2008). In fact, in the USA, such research is considered to be on ‘non-humans'' and, in the absence of institutional rules to the contrary, it would theoretically not require research ethics approval (www.vanderbilthealth.com/main/25443).… the ethics norms that govern clinical research are not suited for the wide range of data privacy and consent issues in today''s social networks and bioinformatics systemsNevertheless, if the samples or data of an individual are accessible in more than one repository or on DTC internet sites, a remote possibility remains that any given individual could be re-identified (Homer et al, 2008). To prevent the restriction of open access to public databases, owing to the fear of re-identifiability, a more reasonable approach is necessary; “[t]his means that a mere hypothetical possibility to single out the individual is not enough to consider the persons as ‘identifiable''” (Data Protection Working Party, 2007). This is a proportionate and important approach because fundamental genomic ‘maps'' such as the International HapMap Project (www.hapmap.org) and the 1000 Genomes project (www.1000genomes.org) have stated as their goal “to make data as widely available as possible to further scientific progress” (Kaye et al, 2009). What then of the nature of the consent and privacy protections in DTC genetic testing?The Personal Genome Project makes the genetic and medical data of its volunteers publicly available. Indeed, there is a marked absence of the traditional confidentiality and other protections of the physician–patient relationship across such sites; overall, the degree of privacy protection by commercial DTC and other sequencing enterprises varies. The company 23andMe allows consumers to choose whether they wish to disclose personal information, but warns that disclosure of personal information is also possible “through other means not associated with 23andMe, […] to friends and/or family members […] and other individuals”. 23andMe also announces that it might enter into commercial or other partnerships for access to its databases (www.23andme.com). deCODEme offers tiered levels of visibility, but does not grant access to third parties in the absence of explicit consumer authorization (www.decodeme.com). GeneEssence will share coded DNA samples with other parties and can transfer or sell personal information or samples with an opt-out option according to their Privacy Policy, though the terms of the latter can be changed at any time (www.geneessence.com). Navigenics is transparent: “If you elect to contribute your genetic information to science through the Navigenics service, you allow us to share Your Genetic Data and Your Phenotype Information with not-for-profit organizations who perform genetic or medical research” (www.navigenics.com). Finally, SeqWright separates the personal information of its clients from their genetic information so as to avoid access to the latter in the case of a security breach (www.seqwright.com).Much has been said about the lack of clinical utility and validity of DTC genetic testing services (Howard & Borry, 2009), to say nothing of the absence of genetic counsellors or physicians to interpret the resulting probabilistic information (Knoppers & Avard, 2009; Wright & Kroese, 2010). But what are the implications for consent and privacy considering the seemingly divergent needs of ensuring data sharing in population projects and ‘protecting'' consumer-citizens in the marketplace?At first glance, the same accusations of paternalism levelled at ethics review committees who hesitate to respect the broad consent of participants in population databases could be applied to restraining the very same citizens from genetic ‘info-voyeurism'' on the internet. But, it should be remembered that citizen empowerment, which enables their participation both in population projects and in DTC, is expressed within very different contexts. Population biobanks, by the very fact of their broad consent and long-term nature, have complex security systems and are subject to governance and ongoing ethical monitoring and review. In addition, independent committees evaluate requests for access (Knoppers & Abdul-Rahman, 2010). The same cannot be said for the governance of the DTC companies just presented.There is room for improvement in both the personal genome and the population genome endeavours. The former require regulatory approaches to ensure the quality, safety, security and utility of their services. The latter require further clarification of their ongoing funding and operations and more transparency to the public as researchers begin to access these resources for disease-specific studies (Institute of Medicine, 2009). Public genomic databases should be interoperable and grant access to authenticated researchers internationally in order to be of utility and statistical significance (Burton et al, 2009). Moreover, to enable international access to such databases for disease-specific research means that the interests of publicly funded research and privacy protection must be weighed against each other, rather than imposing a requirement that research has to demonstrate that the public interest substantially outweighs privacy protection (Weisbrot, 2009). Collaboration through interoperability has been one of the goals of the Public Population Project in Genomics (P³G; www.p3g.org) and, more recently, of the Biobanking and Biomolecular Resources Research Infrastructure (www.bbmri.eu).Even if the tools for harmonization and standardization are built and used, will trans-border data flow still be stymied by privacy concerns? The mutual recognition between countries of privacy equivalent approaches—that is, safe harbour—the limiting of access to approved researchers and the development of international best practices in privacy, security and transparency through a Code of Conduct along with a system for penalizing those who fail to respect such norms, would go some way towards maintaining public trust in genomic and genetic research (P3G Consortium et al, 2009). Finally, consumer protection agencies should monitor DTC sites under a regulatory regime, to ensure that these companies adhere to their own privacy policies.… genetic information is probabilistic and participating in population or on-line studies may not create the fatalistic and harmful discriminatory scenarios originally perceived or imaginedMore importantly in both contexts, the ethics norms that govern clinical research are not suited for the wide range of data privacy and consent issues in today''s social networks and bioinformatics systems. One could go further and ask whether the current biomedical ethics review system is inadequate—if not inappropriate—in these ‘data-driven research'' contexts. Perhaps it is time to create ethics review and oversight systems that are particularly adapted for those citizens who seek either to participate through online services or to contribute to population research resources. Both are contexts of minimal risk and require structural governance reforms rather than the application of traditional ethics consent and privacy review processes that are more suited to clinical research involving drugs or devices. In this information age, genetic information is probabilistic, and participating in population or online studies might not create the fatalistic and harmful discriminatory scenarios originally perceived or imagined. The time is ripe for a change in governance and regulatory approaches, a reform that is consistent with what citizens seem to have already understood and acted on.? Open in a separate windowBartha Maria Knoppers