Objective

The goal of this research is to learn how the editorial staffs of bioinformatics and medical informatics journals provide support for cross-community exposure. Models such as co-citation and co-author analysis measure the relationships between researchers; but they do not capture how environments that support knowledge transfer across communities are organized.

Methods

In this paper, we propose a social network analysis model to study how editorial boards integrate researchers from disparate communities. We evaluate our model by building relational networks based on the editorial boards of approximately 40 journals that serve as research outlets in medical informatics and bioinformatics. We track the evolution of editorial relationships through a longitudinal investigation over the years 2000 through 2005.

Results

Our findings suggest that there are research journals that support the collocation of editorial board members from the bioinformatics and medical informatics communities. Network centrality metrics indicate that editorial board members are located in the intersection of the communities and that the number of individuals in the intersection is growing with time.

Conclusions

Social network analysis methods provide insight into the relationships between the medical informatics and bioinformatics communities. The number of editorial board members facilitating the publication intersection of the communities has grown, but the intersection remains dependent on a small group of individuals and fragile.

Significant interest exists in establishing synergistic research in bioinformatics, systems biology and intelligent computing. Supported by the United States National Science Foundation (NSF), International Society of Intelligent Biological Medicine (http://www.ISIBM.org), International Journal of Computational Biology and Drug Design (IJCBDD) and International Journal of Functional Informatics and Personalized Medicine, the ISIBM International Joint Conferences on Bioinformatics, Systems Biology and Intelligent Computing (ISIBM IJCBS 2009) attracted more than 300 papers and 400 researchers and medical doctors world-wide. It was the only inter/multidisciplinary conference aimed to promote synergistic research and education in bioinformatics, systems biology and intelligent computing. The conference committee was very grateful for the valuable advice and suggestions from honorary chairs, steering committee members and scientific leaders including Dr. Michael S. Waterman (USC, Member of United States National Academy of Sciences), Dr. Chih-Ming Ho (UCLA, Member of United States National Academy of Engineering and Academician of Academia Sinica), Dr. Wing H. Wong (Stanford, Member of United States National Academy of Sciences), Dr. Ruzena Bajcsy (UC Berkeley, Member of United States National Academy of Engineering and Member of United States Institute of Medicine of the National Academies), Dr. Mary Qu Yang (United States National Institutes of Health and Oak Ridge, DOE), Dr. Andrzej Niemierko (Harvard), Dr. A. Keith Dunker (Indiana), Dr. Brian D. Athey (Michigan), Dr. Weida Tong (FDA, United States Department of Health and Human Services), Dr. Cathy H. Wu (Georgetown), Dr. Dong Xu (Missouri), Drs. Arif Ghafoor and Okan K Ersoy (Purdue), Dr. Mark Borodovsky (Georgia Tech, President of ISIBM), Dr. Hamid R. Arabnia (UGA, Vice-President of ISIBM), and other scientific leaders. The committee presented the 2009 ISIBM Outstanding Achievement Awards to Dr. Joydeep Ghosh (UT Austin), Dr. Aidong Zhang (Buffalo) and Dr. Zhi-Hua Zhou (Nanjing) for their significant contributions to the field of intelligent biological medicine.

The advent of high-throughput next generation sequencing technologies have fostered enormous potential applications of supercomputing techniques in genome sequencing, epi-genetics, metagenomics, personalized medicine, discovery of non-coding RNAs and protein-binding sites. To this end, the 2008 International Conference on Bioinformatics and Computational Biology (Biocomp) – 2008 World Congress on Computer Science, Computer Engineering and Applied Computing (Worldcomp) was designed to promote synergistic inter/multidisciplinary research and education in response to the current research trends and advances. The conference attracted more than two thousand scientists, medical doctors, engineers, professors and students gathered at Las Vegas, Nevada, USA during July 14–17 and received great success. Supported by International Society of Intelligent Biological Medicine (ISIBM), International Journal of Computational Biology and Drug Design (IJCBDD), International Journal of Functional Informatics and Personalized Medicine (IJFIPM) and the leading research laboratories from Harvard, M.I.T., Purdue, UIUC, UCLA, Georgia Tech, UT Austin, U. of Minnesota, U. of Iowa etc, the conference received thousands of research papers. Each submitted paper was reviewed by at least three reviewers and accepted papers were required to satisfy reviewers' comments. Finally, the review board and the committee decided to select only 19 high-quality research papers for inclusion in this supplement to BMC Genomics based on the peer reviews only. The conference committee was very grateful for the Plenary Keynote Lectures given by: Dr. Brian D. Athey (University of Michigan Medical School), Dr. Vladimir N. Uversky (Indiana University School of Medicine), Dr. David A. Patterson (Member of United States National Academy of Sciences and National Academy of Engineering, University of California at Berkeley) and Anousheh Ansari (Prodea Systems, Space Ambassador). The theme of the conference to promote synergistic research and education has been achieved successfully.

Supported by National Science Foundation (NSF), International Society of Intelligent Biological Medicine (ISIBM), International Journal of Computational Biology and Drug Design and International Journal of Functional Informatics and Personalized Medicine, IEEE 7th Bioinformatics and Bioengineering attracted more than 600 papers and 500 researchers and medical doctors. It was the only synergistic inter/multidisciplinary IEEE conference with 24 Keynote Lectures, 7 Tutorials, 5 Cutting-Edge Research Workshops and 32 Scientific Sessions including 11 Special Research Interest Sessions that were designed dynamically at Harvard in response to the current research trends and advances. The committee was very grateful for the IEEE Plenary Keynote Lectures given by: Dr. A. Keith Dunker (Indiana), Dr. Jun Liu (Harvard), Dr. Brian Athey (Michigan), Dr. Mark Borodovsky (Georgia Tech and President of ISIBM), Dr. Hamid Arabnia (Georgia and Vice-President of ISIBM), Dr. Ruzena Bajcsy (Berkeley and Member of United States National Academy of Engineering and Member of United States Institute of Medicine of the National Academies), Dr. Mary Yang (United States National Institutes of Health and Oak Ridge, DOE), Dr. Chih-Ming Ho (UCLA and Member of United States National Academy of Engineering and Academician of Academia Sinica), Dr. Andy Baxevanis (United States National Institutes of Health), Dr. Arif Ghafoor (Purdue), Dr. John Quackenbush (Harvard), Dr. Eric Jakobsson (UIUC), Dr. Vladimir Uversky (Indiana), Dr. Laura Elnitski (United States National Institutes of Health) and other world-class scientific leaders. The Harvard meeting was a large academic event 100% full-sponsored by IEEE financially and academically. After a rigorous peer-review process, the committee selected 27 high-quality research papers from 600 submissions. The committee is grateful for contributions from keynote speakers Dr. Russ Altman (IEEE BIBM conference keynote lecturer on combining simulation and machine learning to recognize function in 4D), Dr. Mary Qu Yang (IEEE BIBM workshop keynote lecturer on new initiatives of detecting microscopic disease using machine learning and molecular biology, http://ieeexplore.ieee.org/servlet/opac?punumber=4425386) and Dr. Jack Y. Yang (IEEE BIBM workshop keynote lecturer on data mining and knowledge discovery in translational medicine) from the first IEEE Computer Society BioInformatics and BioMedicine (IEEE BIBM) international conference and workshops, November 2-4, 2007, Silicon Valley, California, USA.

This paper presents the Bioinformatics Computational Journal (BCJ), a framework for conducting and managing computational experiments in bioinformatics and computational biology. These experiments often involve series of computations, data searches, filters, and annotations which can benefit from a structured environment. Systems to manage computational experiments exist, ranging from libraries with standard data models to elaborate schemes to chain together input and output between applications. Yet, although such frameworks are available, their use is not widespread–ad hoc scripts are often required to bind applications together. The BCJ explores another solution to this problem through a computer based environment suitable for on-site use, which builds on the traditional laboratory notebook paradigm. It provides an intuitive, extensible paradigm designed for expressive composition of applications. Extensive features facilitate sharing data, computational methods, and entire experiments. By focusing on the bioinformatics and computational biology domain, the scope of the computational framework was narrowed, permitting us to implement a capable set of features for this domain. This report discusses the features determined critical by our system and other projects, along with design issues. We illustrate the use of our implementation of the BCJ on two domain-specific examples.

The explosion of genome sequencing data along with genotype to phenotype correlation studies has created data deluge in the area of biomedical sciences. The aim of the Medical bioinformatics section is to aid the development and maturation of the field by providing a platform for the translation of these datasets into useful clinical applications. The increase in computing capabilities and availability of different data from advanced technologies will allow researchers to build System Biology models of various diseases in order to efficiently develop new therapeutic interventions and reduce the current prohibitively large costs of drug discovery.

The section welcomes studies on the development of Biomedical Informatics for translational medicine and clinical applications, including tools, methodologies and data integration.

Motivation: With the explosion of biomedical literature and the evolution of online and open access, scientists are reading more articles from a wider variety of journals. Thus, the list of core journals relevant to their research may be less obvious and may often change over time. To help researchers quickly identify appropriate journals to read and publish in, we developed a web application for finding related journals based on the analysis of PubMed log data.

Availability: http://www.ncbi.nlm.nih.gov/IRET/Journals

Contact: luzh@ncbi.nlm.nih.gov

Supplementary information: Supplementary data are available at Bioinformatics online.

The public sharing of primary research datasets potentially benefits the research community but is not yet common practice. In this pilot study, we analyzed whether data sharing frequency was associated with funder and publisher requirements, journal impact factor, or investigator experience and impact. Across 397 recent biomedical microarray studies, we found investigators were more likely to publicly share their raw dataset when their study was published in a high-impact journal and when the first or last authors had high levels of career experience and impact. We estimate the USA’s National Institutes of Health (NIH) data sharing policy applied to 19% of the studies in our cohort; being subject to the NIH data sharing plan requirement was not found to correlate with increased data sharing behavior in multivariate logistic regression analysis. Studies published in journals that required a database submission accession number as a condition of publication were more likely to share their data, but this trend was not statistically significant. These early results will inform our ongoing larger analysis, and hopefully contribute to the development of more effective data sharing initiatives.

Background

The SYMBIOmatics Specific Support Action (SSA) is "an information gathering and dissemination activity" that seeks "to identify synergies between the bioinformatics and the medical informatics" domain to improve collaborative progress between both domains (ref. to ). As part of the project experts in both research fields will be identified and approached through a survey. To provide input to the survey, the scientific literature was analysed to extract topics relevant to both medical informatics and bioinformatics.

Results

This paper presents results of a systematic analysis of the scientific literature from medical informatics research and bioinformatics research. In the analysis pairs of words (bigrams) from the leading bioinformatics and medical informatics journals have been used as indication of existing and emerging technologies and topics over the period 2000–2005 ("recent") and 1990–1990 ("past"). We identified emerging topics that were equally important to bioinformatics and medical informatics in recent years such as microarray experiments, ontologies, open source, text mining and support vector machines. Emerging topics that evolved only in bioinformatics were system biology, protein interaction networks and statistical methods for microarray analyses, whereas emerging topics in medical informatics were grid technology and tissue microarrays.

Conclusion

We conclude that although both fields have their own specific domains of interest, they share common technological developments that tend to be initiated by new developments in biotechnology and computer science.

When the human genome project was conceived, its leaders wanted all researchers to have equal access to the data and associated research tools. Their vision of equal access provides an unprecedented teaching opportunity. Teachers and students have free access to the same databases that researchers are using. Furthermore, the recent movement to deliver scientific publications freely has presented a second source of current information for teaching. I have developed a genomics course that incorporates many of the public-domain databases, research tools, and peer-reviewed journals. These online resources provide students with exciting entree into the new fields of genomics, proteomics, and bioinformatics. In this essay, I outline how these fields are especially well suited for inclusion in the undergraduate curriculum. Assessment data indicate that my students were able to utilize online information to achieve the educational goals of the course and that the experience positively influenced their perceptions of how they might contribute to biology.

The 6th Benelux Bioinformatics Conference (BBC11) held in Luxembourg on 12 and 13 December 2011 attracted around 200 participants, including internationally-renowned guest speakers and more than 100 peer-reviewed submissions from 3 continents. Researchers from the public and private sectors convened at BBC11 to discuss advances and challenges in a wide spectrum of application areas. A key theme of the conference was the contribution of bioinformatics to enable and accelerate translational and clinical research. The BBC11 stressed the need for stronger collaborating efforts across disciplines and institutions. The demonstration of the clinical relevance of systems approaches and of next-generation sequencing-based measurement technologies are among the existing opportunities for increasing impact in translational research. Translational bioinformatics will benefit from research models that strike a balance between the importance of protecting intellectual property and the need to openly access scientific and technological advances. The full conference proceedings are freely available at http://www.bbc11.lu.

This editorial announces Algorithms for Molecular Biology, a new online open access journal published by BioMed Central. By launching the first open access journal on algorithmic bioinformatics, we provide a forum for fast publication of high-quality research articles in this rapidly evolving field. Our journal will publish thoroughly peer-reviewed papers without length limitations covering all aspects of algorithmic data analysis in computatioal biology. Publications in Algorithms for Molecular Biology are easy to find, highly visible and tracked by organisations such as PubMed. An established online submission system makes a fast reviewing procedure possible and enables us to publish accepted papers without delay. All articles published in our journal are permanently archived by PubMed Central and other scientific archives. We are looking forward to receiving your contributions.

Biology has a conceptual basis that allows one to build models and theorize across many life sciences, including medicine and medically-related disciplines. A dearth of good venues for publication has been perceived during a period when bioinformatics, systems analysis and biomathematics are burgeoning.

Steps have been taken to provide the sort of journal with a quick turnaround time for manuscripts which is online and freely accessible to all readers, whatever their persuasion or discipline. We have now been running for some time a journal which has had many good papers presented pre-launch, and a steady stream of papers thereafter. The value of this journal as a new venue has already been vindicated.

Within a short space of time, we have founded a state-of-the-art electronic journal freely accessible to all in a much sort-after interdisciplinary field that will be of benefit to the thinking life scientist, which must include medically qualified doctors as well as scientists who prefer to build their new hypotheses on basic principles and sound concepts underpinning biology. At the same time, these principles are not sacrosanct and require critical analysis. The journal promises to deliver many exciting ideas in the future.

Policies supporting the rapid and open sharing of proteomic data are being implemented by the leading journals in the field. The proteomics community is taking steps to ensure that data are made publicly accessible and are of high quality, a challenging task that requires the development and deployment of methods for measuring and documenting data quality metrics. On September 18, 2010, the U.S. National Cancer Institute (NCI) convened the “International Workshop on Proteomic Data Quality Metrics” in Sydney, Australia, to identify and address issues facing the development and use of such methods for open access proteomics data. The stakeholders at the workshop enumerated the key principles underlying a framework for data quality assessment in mass spectrometry data that will meet the needs of the research community, journals, funding agencies, and data repositories. Attendees discussed and agreed up on two primary needs for the wide use of quality metrics: (1) an evolving list of comprehensive quality metrics and (2) standards accompanied by software analytics. Attendees stressed the importance of increased education and training programs to promote reliable protocols in proteomics. This workshop report explores the historic precedents, key discussions, and necessary next steps to enhance the quality of open access data.

By agreement, this article is published simultaneously in the Journal of Proteome Research, Molecular and Cellular Proteomics, Proteomics, and Proteomics Clinical Applications as a public service to the research community. The peer review process was a coordinated effort conducted by a panel of referees selected by the journals.

In today’s proteomics research, various techniques and instrumentation bioinformatics tools are necessary to manage the large amount of heterogeneous data with an automatic quality control to produce reliable and comparable results. Therefore a data-processing pipeline is mandatory for data validation and comparison in a data-warehousing system. The proteome bioinformatics platform ProteinScape has been proven to cover these needs. The reprocessing of HUPO BPP participants’ MS data was done within ProteinScape. The reprocessed information was transferred into the global data repository PRIDE.

ProteinScape as a data-warehousing system covers two main aspects: archiving relevant data of the proteomics workflow and information extraction functionality (protein identification, quantification and generation of biological knowledge). As a strategy for automatic data validation, different protein search engines are integrated. Result analysis is performed using a decoy database search strategy, which allows the measurement of the false-positive identification rate. Peptide identifications across different workflows, different MS techniques, and different search engines are merged to obtain a quality-controlled protein list.

The proteomics identifications database (PRIDE), as a public data repository, is an archiving system where data are finally stored and no longer changed by further processing steps. Data submission to PRIDE is open to proteomics laboratories generating protein and peptide identifications. An export tool has been developed for transferring all relevant HUPO BPP data from ProteinScape into PRIDE using the PRIDE.xml format.

The EU-funded ProDac project will coordinate the development of software tools covering international standards for the representation of proteomics data. The implementation of data submission pipelines and systematic data collection in public standards–compliant repositories will cover all aspects, from the generation of MS data in each laboratory to the conversion of all the annotating information and identifications to a standardized format. Such datasets can be used in the course of publishing in scientific journals.

Motivation

There is extensive interest in automating the collection, organization, and analysis of biological data. Data in the form of images in online literature present special challenges for such efforts. The first steps in understanding the contents of a figure are decomposing it into panels and determining the type of each panel. In biological literature, panel types include many kinds of images collected by different techniques, such as photographs of gels or images from microscopes. We have previously described the SLIF system (http://slif.cbi.cmu.edu) that identifies panels containing fluorescence microscope images among figures in online journal articles as a prelude to further analysis of the subcellular patterns in such images. This system contains a pretrained classifier that uses image features to assign a type (class) to each separate panel. However, the types of panels in a figure are often correlated, so that we can consider the class of a panel to be dependent not only on its own features but also on the types of the other panels in a figure.

Results

In this paper, we introduce the use of a type of probabilistic graphical model, a factor graph, to represent the structured information about the images in a figure, and permit more robust and accurate inference about their types. We obtain significant improvement over results for considering panels separately.

Availability

The code and data used for the experiments described here are available from http://murphylab.web.cmu.edu/software. Contact: murphy@cmu.edu

In a number of estimation problems in bioinformatics, accuracy measures of the target problem are usually given, and it is important to design estimators that are suitable to those accuracy measures. However, there is often a discrepancy between an employed estimator and a given accuracy measure of the problem. In this study, we introduce a general class of efficient estimators for estimation problems on high-dimensional binary spaces, which represent many fundamental problems in bioinformatics. Theoretical analysis reveals that the proposed estimators generally fit with commonly-used accuracy measures (e.g. sensitivity, PPV, MCC and F-score) as well as it can be computed efficiently in many cases, and cover a wide range of problems in bioinformatics from the viewpoint of the principle of maximum expected accuracy (MEA). It is also shown that some important algorithms in bioinformatics can be interpreted in a unified manner. Not only the concept presented in this paper gives a useful framework to design MEA-based estimators but also it is highly extendable and sheds new light on many problems in bioinformatics.

Online learning initiatives over the past decade have become increasingly comprehensive in their selection of courses and sophisticated in their presentation, culminating in the recent announcement of a number of consortium and startup activities that promise to make a university education on the internet, free of charge, a real possibility. At this pivotal moment it is appropriate to explore the potential for obtaining comprehensive bioinformatics training with currently existing free video resources. This article presents such a bioinformatics curriculum in the form of a virtual course catalog, together with editorial commentary, and an assessment of strengths, weaknesses, and likely future directions for open online learning in this field.

Designers have a saying that “the joy of an early release lasts but a short time. The bitterness of an unusable system lasts for years.” It is indeed disappointing to discover that your data resources are not being used to their full potential. Not only have you invested your time, effort, and research grant on the project, but you may face costly redesigns if you want to improve the system later. This scenario would be less likely if the product was designed to provide users with exactly what they need, so that it is fit for purpose before its launch. We work at EMBL-European Bioinformatics Institute (EMBL-EBI), and we consult extensively with life science researchers to find out what they need from biological data resources. We have found that although users believe that the bioinformatics community is providing accurate and valuable data, they often find the interfaces to these resources tricky to use and navigate. We believe that if you can find out what your users want even before you create the first mock-up of a system, the final product will provide a better user experience. This would encourage more people to use the resource and they would have greater access to the data, which could ultimately lead to more scientific discoveries. In this paper, we explore the need for a user-centred design (UCD) strategy when designing bioinformatics resources and illustrate this with examples from our work at EMBL-EBI. Our aim is to introduce the reader to how selected UCD techniques may be successfully applied to software design for bioinformatics.

The field of bioinformatics and computational biology has gone through a number of transformations during the past 15 years, establishing itself as a key component of new biology. This spectacular growth has been challenged by a number of disruptive changes in science and technology. Despite the apparent fatigue of the linguistic use of the term itself, bioinformatics has grown perhaps to a point beyond recognition. We explore both historical aspects and future trends and argue that as the field expands, key questions remain unanswered and acquire new meaning while at the same time the range of applications is widening to cover an ever increasing number of biological disciplines. These trends appear to be pointing to a redefinition of certain objectives, milestones, and possibly the field itself.

The ability to manage the constantly growing clinically relevant information in genetics available on the internet is becoming crucial in medical practice. Therefore, training students in teaching environments that develop bioinformatics skills is a particular challenge to medical schools. We present here an instructional approach that potentiates learning of hormone/vitamin mechanisms of action in gene regulation with the acquisition and practice of bioinformatics skills. The activity is integrated within the study of the Endocrine System module. Given a nucleotide sequence of a hormone or vitamin-response element, students use internet databases and tools to find the gene to which it belongs. Subsequently, students search how the corresponding hormone/vitamin influences the expression of that particular gene and how a dysfunctional interaction might cause disease. This activity was presented for four consecutive years to cohorts of 50–60 students/year enrolled in the 2nd year of the medical degree. 90% of the students developed a better understanding of the usefulness of bioinformatics and 98% intend to use web-based resources in the future. Since hormones and vitamins regulate genes of all body organ systems, this activity successfully integrates the whole body physiology of the medical curriculum.

Background

Recently, various evolution-related journals adopted policies to encourage or require archiving of phylogenetic trees and associated data. Such attention to practices that promote sharing of data reflects rapidly improving information technology, and rapidly expanding potential to use this technology to aggregate and link data from previously published research. Nevertheless, little is known about current practices, or best practices, for publishing trees and associated data so as to promote re-use.

Findings

Here we summarize results of an ongoing analysis of current practices for archiving phylogenetic trees and associated data, current practices of re-use, and current barriers to re-use. We find that the technical infrastructure is available to support rudimentary archiving, but the frequency of archiving is low. Currently, most phylogenetic knowledge is not easily re-used due to a lack of archiving, lack of awareness of best practices, and lack of community-wide standards for formatting data, naming entities, and annotating data. Most attempts at data re-use seem to end in disappointment. Nevertheless, we find many positive examples of data re-use, particularly those that involve customized species trees generated by grafting to, and pruning from, a much larger tree.

Conclusions

The technologies and practices that facilitate data re-use can catalyze synthetic and integrative research. However, success will require engagement from various stakeholders including individual scientists who produce or consume shareable data, publishers, policy-makers, technology developers and resource-providers. The critical challenges for facilitating re-use of phylogenetic trees and associated data, we suggest, include: a broader commitment to public archiving; more extensive use of globally meaningful identifiers; development of user-friendly technology for annotating, submitting, searching, and retrieving data and their metadata; and development of a minimum reporting standard (MIAPA) indicating which kinds of data and metadata are most important for a re-useable phylogenetic record.

Differential transcription in Ascaris suum was investigated using a genomic-bioinformatic approach. A cDNA archive enriched for molecules in the infective third-stage larva (L3) of A. suum was constructed by suppressive-subtractive hybridization (SSH), and a subset of cDNAs from 3075 clones subjected to microarray analysis using cDNA probes derived from RNA from different developmental stages of A. suum. The cDNAs (n = 498) shown by microarray analysis to be enriched in the L3 were sequenced and subjected to bioinformatic analyses using a semi-automated pipeline (ESTExplorer). Using gene ontology (GO), 235 of these molecules were assigned to ‘biological process’ (n = 68), ‘cellular component’ (n = 50), or ‘molecular function’ (n = 117). Of the 91 clusters assembled, 56 molecules (61.5%) had homologues/orthologues in the free-living nematodes Caenorhabditis elegans and C. briggsae and/or other organisms, whereas 35 (38.5%) had no significant similarity to any sequences available in current gene databases. Transcripts encoding protein kinases, protein phosphatases (and their precursors), and enolases were abundantly represented in the L3 of A. suum, as were molecules involved in cellular processes, such as ubiquitination and proteasome function, gene transcription, protein–protein interactions, and function. In silico analyses inferred the C. elegans orthologues/homologues (n = 50) to be involved in apoptosis and insulin signaling (2%), ATP synthesis (2%), carbon metabolism (6%), fatty acid biosynthesis (2%), gap junction (2%), glucose metabolism (6%), or porphyrin metabolism (2%), although 34 (68%) of them could not be mapped to a specific metabolic pathway. Small numbers of these 50 molecules were predicted to be secreted (10%), anchored (2%), and/or transmembrane (12%) proteins. Functionally, 17 (34%) of them were predicted to be associated with (non-wild-type) RNAi phenotypes in C. elegans, the majority being embryonic lethality (Emb) (13 types; 58.8%), larval arrest (Lva) (23.5%) and larval lethality (Lvl) (47%). A genetic interaction network was predicted for these 17 C. elegans orthologues, revealing highly significant interactions for nine molecules associated with embryonic and larval development (66.9%), information storage and processing (5.1%), cellular processing and signaling (15.2%), metabolism (6.1%), and unknown function (6.7%). The potential roles of these molecules in development are discussed in relation to the known roles of their homologues/orthologues in C. elegans and some other nematodes. The results of the present study provide a basis for future functional genomic studies to elucidate molecular aspects governing larval developmental processes in A. suum and/or the transition to parasitism.

Author Summary

In the present study, we constructed a cDNA library enriched for molecules of the infective third-stage larva (L3) of Ascaris suum, the common roundworm of pigs. Using the method of suppressive-subtractive hybridization (SSH), we explored transcription of a subset of molecules by microarray analysis and conducted bioinformatic analyses to characterize these molecules, map them to biochemical pathways, and predict genetic interactions based on comparisons with Caenorhabditis elegans and/or other organisms. The results provide interesting insights into early molecular processes in A. suum. Approximately 60% of the L3-enriched molecules discovered had homologues in C. elegans. Probabilistic analyses suggested that a complex genetic network regulates or controls larval growth and development in A. suum L3s, some of which might be involved in or regulate the switch from the free-living to the parasitic stage. Functional studies of these molecules to elucidate developmental processes in Ascaris could assist in identifying new targets for intervention.

The application of whole-genome shotgun sequencing to microbial communities represents a major development in metagenomics, the study of uncultured microbes via the tools of modern genomic analysis. In the past year, whole-genome shotgun sequencing projects of prokaryotic communities from an acid mine biofilm, the Sargasso Sea, Minnesota farm soil, three deep-sea whale falls, and deep-sea sediments have been reported, adding to previously published work on viral communities from marine and fecal samples. The interpretation of this new kind of data poses a wide variety of exciting and difficult bioinformatics problems. The aim of this review is to introduce the bioinformatics community to this emerging field by surveying existing techniques and promising new approaches for several of the most interesting of these computational problems.

Despite advanced immunosuppression, redundancy in the molecular diversity of acute rejection (AR) often results in incomplete resolution of the injury response. We present a bioinformatics based approach for identification of these redundant molecular pathways in AR and a drug repositioning approach to suppress these using FDA approved drugs currently available for non-transplant indications. Two independent microarray data-sets from human renal allograft biopsies (n = 101) from patients on majorly Th1/IFN-y immune response targeted immunosuppression, with and without AR, were profiled. Using gene-set analysis across 3305 biological pathways, significant enrichment was found for the IL17 pathway in AR in both data-sets. Recent evidence suggests IL17 pathway as an important escape mechanism when Th1/IFN-y mediated responses are suppressed. As current immunosuppressions do not specifically target the IL17 axis, 7200 molecular compounds were interrogated for FDA approved drugs with specific inhibition of this axis. A combined IL17/IFN-y suppressive role was predicted for the antilipidemic drug Fenofibrate. To assess the immunregulatory action of Fenofibrate, we conducted in-vitro treatment of anti-CD3/CD28 stimulated human peripheral blood cells (PBMC), and, as predicted, Fenofibrate reduced IL17 and IFN-γ gene expression in stimulated PMBC. In-vivo Fenofibrate treatment of an experimental rodent model of cardiac AR reduced infiltration of total leukocytes, reduced expression of IL17/IFN-y and their pathway related genes in allografts and recipients’ spleens, and extended graft survival by 21 days (p<0.007). In conclusion, this study provides important proof of concept that meta-analyses of genomic data and drug databases can provide new insights into the redundancy of the rejection response and presents an economic methodology to reposition FDA approved drugs in organ transplantation.