Information management for proteomics: a perspective

Proteomics is a data-rich discipline that makes extensive use of separation tools, mass spectrometry and bioinformatics to analyze and interpret the features and dynamics of the proteome. A major challenge for the field is how proteomics data can be stored and managed, such that data become permanent and can be mined with current and future tools. This article details our experience in the development of a commercial proteomic information management system. We identify the challenges faced in data acquisition, workflow management, data permanence, security, data interpretation and analysis, as well as the solutions implemented to address these issues. We finally provide a perspective on data management in proteomics and the implications for academic and industry-based researchers working in this field.     

Information management for proteomics: a perspective

Proteomics is a data-rich discipline that makes extensive use of separation tools, mass spectrometry and bioinformatics to analyze and interpret the features and dynamics of the proteome. A major challenge for the field is how proteomics data can be stored and managed, such that data become permanent and can be mined with current and future tools. This article details our experience in the development of a commercial proteomic information management system. We identify the challenges faced in data acquisition, workflow management, data permanence, security, data interpretation and analysis, as well as the solutions implemented to address these issues. We finally provide a perspective on data management in proteomics and the implications for academic and industry-based researchers working in this field.     

Scientific perspectivism: A philosopher of science's response to the challenge of big data biology

Big data biology—bioinformatics, computational biology, systems biology (including ‘omics’), and synthetic biology—raises a number of issues for the philosophy of science. This article deals with several such: Is data-intensive biology a new kind of science, presumably post-reductionistic? To what extent is big data biology data-driven? Can data ‘speak for themselves?’ I discuss these issues by way of a reflection on Carl Woese’s worry that “a society that permits biology to become an engineering discipline, that allows that science to slip into the role of changing the living world without trying to understand it, is a danger to itself.” And I argue that scientific perspectivism, a philosophical stance represented prominently by Giere, Van Fraassen, and Wimsatt, according to which science cannot as a matter of principle transcend our human perspective, provides the best resources currently at our disposal to tackle many of the philosophical issues implied in the modeling of complex, multilevel/multiscale phenomena.     

Using provenance to manage knowledge of in silico experiments

This article offers a briefing in one of the knowledge management issues of in silico experimentation in bioinformatics. Recording of the provenance of an experiment-what was done; where, how and why, etc. is an important aspect of scientific best practice that should be extended to in silico experimentation. We will do this in the context of eScience which has been part of the move of bioinformatics towards an industrial setting. Despite the computational nature of bioinformatics, these analyses are scientific and thus necessitate their own versions of typical scientific rigour. Just as recording who, what, why, when, where and how of an experiment is central to the scientific process in laboratory science, so it should be in silico science. The generation and recording of these aspects, or provenance, of an experiment are necessary knowledge management goals if we are to introduce scientific rigour into routine bioinformatics. In Silico experimental protocols should themselves be a form of managing the knowledge of how to perform bioinformatics analyses. Several systems now exist that offer support for the generation and collection of provenance information about how a particular in silico experiment was run, what results were generated, how they were generated, etc. In reviewing provenance support, we will review one of the important knowledge management issues in bioinformatics.     

Thriving in Multidisciplinary Research: Advice for New Bioinformatics Students

The sciences have seen a large increase in demand for students in bioinformatics and multidisciplinary fields in general. Many new educational programs have been created to satisfy this demand, but navigating these programs requires a non-traditional outlook and emphasizes working in teams of individuals with distinct yet complementary skill sets. Written from the perspective of a current bioinformatics student, this article seeks to offer advice to prospective and current students in bioinformatics regarding what to expect in their educational program, how multidisciplinary fields differ from more traditional paths, and decisions that they will face on the road to becoming successful, productive bioinformaticists.     

BioManager: the use of a bioinformatics web application as a teaching tool in undergraduate bioinformatics training

The completion of the human genome project, and other genome sequencing projects, has spearheaded the emergence of the field of bioinformatics. Using computer programs to analyse DNA and protein information has become an important area of life science research and development. While it is not necessary for most life science researchers to develop specialist bioinformatic skills (including software development), basic skills in the application of common bioinformatics software and the effective interpretation of results are increasingly required by all life science researchers. Training in bioinformatics is increasingly occurring within the university system as part of existing undergraduate science and specialist degrees. One difficulty in bioinformatics education is the sheer number of software programs required in order to provide a thorough grounding in the subject to the student. Teaching requires either a well-maintained internal server with all the required software, properly interfacing with student terminals, and with sufficient capacity to handle multiple simultaneous requests, or it requires the individual installation and maintenance of every piece of software on each computer. In both cases, there are difficult issues regarding site maintenance and accessibility. In this article, we discuss the use of BioManager, a web-based bioinformatics application integrating a variety of common bioinformatics tools, for teaching, including its role as the main bioinformatics training tool in some Australian and international universities. We discuss some of the issues with using a bioinformatics resource primarily created for research in an undergraduate teaching environment.     

Bioinformatics and data-intensive scientific discovery in the beginning of the 21st century

This article is a summary of the bioinformatics issues and challenges of data-intensive science as discussed in the NSF-funded Data-Intensive Science (DIS) workshop in Seattle, September 19-20, 2010.     

Forensic DNA and bioinformatics

The field of forensic science is increasingly based on biomolecular data and many European countries are establishing forensic databases to store DNA profiles of crime scenes of known offenders and apply DNA testing. The field is boosted by statistical and technological advances such as DNA microarray sequencing, TFT biosensors, machine learning algorithms, in particular Bayesian networks, which provide an effective way of evidence organization and inference. The aim of this article is to discuss the state of art potentialities of bioinformatics in forensic DNA science. We also discuss how bioinformatics will address issues related to privacy rights such as those raised from large scale integration of crime, public health and population genetic susceptibility-to-diseases databases.     

蛋白质/核酸相互作用研究方法进展

蛋白质和核酸是构成生命体最为重要的两类生物大分子,蛋白质与核酸的相互作用是分子生物学研究的中心问题之一,它是许多生命活动的重要组成部分。研究蛋白质/核酸相互作用近期采用的新技术有:核酸适体技术、生物信息学方法、蛋白质芯片技术以及纳米技术等。本文就这些新的研究方法进行综述。     

Experience using web services for biological sequence analysis

Programmatic access to data and tools through the web using so-called web services has an important role to play in bioinformatics. In this article, we discuss the most popular approaches based on SOAP/WS-I and REST and describe our, a cross section of the community, experiences with providing and using web services in the context of biological sequence analysis. We briefly review main technological approaches as well as best practice hints that are useful for both users and developers. Finally, syntactic and semantic data integration issues with multiple web services are discussed.     

Bioinformatics Goes to School—New Avenues for Teaching Contemporary Biology

Since 2010, the European Molecular Biology Laboratory''s (EMBL) Heidelberg laboratory and the European Bioinformatics Institute (EMBL-EBI) have jointly run bioinformatics training courses developed specifically for secondary school science teachers within Europe and EMBL member states. These courses focus on introducing bioinformatics, databases, and data-intensive biology, allowing participants to explore resources and providing classroom-ready materials to support them in sharing this new knowledge with their students.In this article, we chart our progress made in creating and running three bioinformatics training courses, including how the course resources are received by participants and how these, and bioinformatics in general, are subsequently used in the classroom. We assess the strengths and challenges of our approach, and share what we have learned through our interactions with European science teachers.     

A review of bioinformatics education in the UK

If the completion of the first draft of the human genome represents the coming of age of bioinformatics, then the emergence of bioinformatics as a university degree subject represents its establishment. In this paper bioinformatics as a subject for formal study is discussed, rather than as a subject for research, and a selection of the taught, mainly graduate, courses currently available in the UK are reviewed. Throughout, the author tries to draw parallels between the integration of bioinformatics into biomedical research and teaching today, and that of molecular biology, two decades ago. Others have made this analogy between these two relatively young disciplines. Although research sources are referenced, the author makes no pretence of objectivity. This article contains his opinions, and those of a number of current bioinformatics course organisers whose comments on the subject were solicited in advance specifically for this paper. The course organisers kindly advised how they planned their curricula, and described the special strengths of their programmes. Comments from present and former students of several bioinformatics degree programmes were also solicited. Except where individuals are directly quoted, any opinions expressed herein should be considered the author's. Compared with its sister piece [Marion Zatz, in previous issue of Briefings in Bioinformatics pp. 353], this paper is less about funding policy--which, in the UK, has lately (if belatedly) been more generous towards bioinformatics teaching--than it is about practice and content; the requirements of the bioinformatics research communities, the corresponding emphases of bioinformatics courses, and the general market for holders of bioinformatics degrees. Individual courses are cited throughout as examples, but the final section contains a full annotated listing with URL addresses. Based on the author's own experience of practising and teaching bioinformatics, he describes the skills he believes will be most useful to bioinformaticians in the near future and suggests ways to prepare students of bioinformatics for a fall in demand for those abilities.     

Exploring the Synergy Between Industrial Ecology and System of Systems to Understand Complexity

Two objectives are pursued in this article. First, from a methodological perspective, we explore the relationships among the constructs of complex adaptive systems, systems of systems, and industrial ecology. Through examination of central traits of each, we find that industrial ecology and system of systems present complementary frameworks for posing systemic problems in the context of sociotechnical applications. Furthermore, we contend that complexity science (the basis for the study of complex adaptive systems) provides a natural and necessary foundation and set of tools to analyze mechanisms such as evolution, emergence, and regulation in these applications. The second objective of the article is to illustrate the use of two tools from complexity sciences to address a network transition problem in air transportation framed from the system-of-systems viewpoint and shaped by an industrial ecology perspective. A stochastic simulation consisting of network theory analysis combined with agent-based modeling to study the evolution of an air transport network is presented. Patterns in agent behavior that lead to preferred outcomes across two scenarios are observed, and the implications of these results for decision makers are described. Furthermore, we highlight the necessity for future efforts to combine the merits of both system of systems and industrial ecology in tackling the issues of complexity in such large-scale, sociotechnical problems.     

2D electrophoresis-based expression proteomics: a microbiologist's perspective

Quantitative proteomics based on 2D electrophoresis (2-DE) coupled with peptide mass fingerprinting is still one of the most widely used quantitative proteomics approaches in microbiology research. Our view on the exploitation of this global expression analysis technique and its contribution and potential to push forward the field of molecular microbial physiology towards a molecular systems microbiology perspective is discussed in this article. The advances registered in 2-DE-based quantitative proteomic analysis leading to increased protein resolution, sensitivity and accuracy, and the promising use of 2-DE to gain insights into post-translational modifications at a proteome-wide level (considering all the proteins/protein forms expressed by the genome) are focused on. Given the progress made in this field, it is foreseen that the 2-DE-based approach to quantitative proteomics will continue to be a fundamental tool for microbiologists working at a genome-wide scale. Guidelines are also provided for the exploitation of expression proteomics data, based on useful computational tools, and for the integration of these data with other genome-wide expression information. The advantages and limitations of a complete 2-DE-based expression proteomics analysis, envisaging the quantification of the global changes occurring in the proteome of a given cell depending on environmental or genetic manipulations, are discussed from the microbiologist's perspective. Particular focus is given to the emerging field of toxicoproteomics, a new systems toxicity approach that offers a powerful tool to directly monitor the earliest stages of the toxicological response by identifying critical proteins and pathways that are affected by, and respond to, a chemical stress. The experimental design and the bioinformatics analysis of data used in our laboratory to gain mechanistic insights through expression proteomics into the responses of the eukaryotic model Saccharomyces cerevisiae or of Pseudomonas strains to environmental toxicants are presented as case studies.     

2D electrophoresis-based expression proteomics: a microbiologist’s perspective

Quantitative proteomics based on 2D electrophoresis (2-DE) coupled with peptide mass fingerprinting is still one of the most widely used quantitative proteomics approaches in microbiology research. Our view on the exploitation of this global expression analysis technique and its contribution and potential to push forward the field of molecular microbial physiology towards a molecular systems microbiology perspective is discussed in this article. The advances registered in 2-DE-based quantitative proteomic analysis leading to increased protein resolution, sensitivity and accuracy, and the promising use of 2-DE to gain insights into post-translational modifications at a proteome-wide level (considering all the proteins/protein forms expressed by the genome) are focused on. Given the progress made in this field, it is foreseen that the 2-DE-based approach to quantitative proteomics will continue to be a fundamental tool for microbiologists working at a genome-wide scale. Guidelines are also provided for the exploitation of expression proteomics data, based on useful computational tools, and for the integration of these data with other genome-wide expression information. The advantages and limitations of a complete 2-DE-based expression proteomics analysis, envisaging the quantification of the global changes occurring in the proteome of a given cell depending on environmental or genetic manipulations, are discussed from the microbiologist’s perspective. Particular focus is given to the emerging field of toxicoproteomics, a new systems toxicity approach that offers a powerful tool to directly monitor the earliest stages of the toxicological response by identifying critical proteins and pathways that are affected by, and respond to, a chemical stress. The experimental design and the bioinformatics analysis of data used in our laboratory to gain mechanistic insights through expression proteomics into the responses of the eukaryotic model Saccharomyces cerevisiae or of Pseudomonas strains to environmental toxicants are presented as case studies.     

In-Silico Pharmacodynamics

Adverse effects are exhibited by most drugs in current clinical practice, the causes for which are often not known. In this post genomic era, bioinformatics has the potential to address several issues in understanding the mechanism of drug action and in designing improved drugs. This study describes the analysis of the possible pharmacodynamic behaviour of antihistamines blocking the histamine H(2) receptor (H(2)-antihistamines), by adopting the basic tenets of a systems biology approach. The different components that could form an appropriate sub-system are identified, thus providing a system landscape. Docking and analysis of the chosen antihistamines into each of these components resulted in identifying histamine N-methyl transferase (HNMT) as a potential unintended target for H(2)-antihistamines. Correlation with experimental data available from the literature indicates the inhibition of HNMT to be a possible cause for the adverse effects exhibited by these drugs. Implications for design of safer H(2)-antihistamines are discussed. The method reported here has the potential for application as a general strategy in understanding drug effects.     

Resilience Theory in Archaeology

The past can be characterized by periods of changing and stable relationships between human groups and their environment. In this article, I argue that use of "resilience theory" as a conceptual framework will assist archaeologists in interpreting the past in ways that are interesting and potentially relevant to contemporary issues. Many of the authors in this "In Focus" section primarily concentrate on the relationships associated with patterns of human extraction of resources and the impacts of those human activities on the continuing condition of the ecosystem. These processes are, of course, embedded in a complex web of relationships that are based on multiple interactions of underlying patterns and processes of both the ecological and social domains. In this article, I introduce a resilience theory perspective to argue that these transformations were characterized by very different reorganizations of the socioecological landscape and were the product of a variety of factors that operated at different scales of geography, time, and social organization.     

Evolving from bioinformatics in-the-small to bioinformatics in-the-large

We argue the significance of a fundamental shift in bioinformatics, from in-the-small to in-the-large. Adopting a large-scale perspective is a way to manage the problems endemic to the world of the small-constellations of incompatible tools for which the effort required to assemble an integrated system exceeds the perceived benefit of the integration. Where bioinformatics in-the-small is about data and tools, bioinformatics in-the-large is about metadata and dependencies. Dependencies represent the complexities of large-scale integration, including the requirements and assumptions governing the composition of tools. The popular make utility is a very effective system for defining and maintaining simple dependencies, and it offers a number of insights about the essence of bioinformatics in-the-large. Keeping an in-the-large perspective has been very useful to us in large bioinformatics projects. We give two fairly different examples, and extract lessons from them showing how it has helped. These examples both suggest the benefit of explicitly defining and managing knowledge flows and knowledge maps (which represent metadata regarding types, flows, and dependencies), and also suggest approaches for developing bioinformatics database systems. Generally, we argue that large-scale engineering principles can be successfully adapted from disciplines such as software engineering and data management, and that having an in-the-large perspective will be a key advantage in the next phase of bioinformatics development.     

Workshops: A Great Way to Enhance and Supplement a Degree

As part of the International Society for Computational Biology Student Council (ISCB-SC), Regional Student Groups (RSGs) have helped organise workshops in the emerging fields of bioinformatics and computational biology. Workshops are a great way for students to gain hands-on experience and rapidly acquire knowledge in advanced research topics where curriculum-based education is yet to be developed. RSG workshops have improved dissemination of knowledge of the latest bioinformatics techniques and resources among student communities and young scientists, especially in developing nations. This article highlights some of the benefits and challenges encountered while running RSG workshops. Examples cover a variety of subjects, including introductory bioinformatics and advanced bioinformatics, as well as soft skills such as networking, career development, and socializing. The collective experience condensed in this article is a useful starting point for students wishing to organise their own tailor-made workshops.     

Novel proteomic approaches for tissue analysis

Proteomics, the global study of protein expression and characteristics, has recently emerged as a key component in the field of molecular analysis. The dynamic nature of proteins, from ion channels to chaperones, presents a challenge, yet the understanding of these molecules provides a rich source of information. When applying proteomic analysis directly to human tissue samples, additional difficulties arise. The following article presents an overview of the current proteomic tools used in the analysis of tissues, beginning with conventional methods such as western blot analysis and 2D polyacrylamide gel electrophoresis. The most current high-throughput techniques being used today are also reviewed. These include protein arrays, reverse-phase protein lysate arrays, matrix-assisted laser desorption/ionization, surface-enhanced laser desorption/ionization and layered expression scanning. In addition, bioinformatics as well as issues regarding tissue preservation and microdissection to obtain pure cell populations are included. Finally, future directions of the tissue proteomics field are discussed.