Literature mining for the biologist: from information retrieval to biological discovery

For the average biologist, hands-on literature mining currently means a keyword search in PubMed. However, methods for extracting biomedical facts from the scientific literature have improved considerably, and the associated tools will probably soon be used in many laboratories to automatically annotate and analyse the growing number of system-wide experimental data sets. Owing to the increasing body of text and the open-access policies of many journals, literature mining is also becoming useful for both hypothesis generation and biological discovery. However, the latter will require the integration of literature and high-throughput data, which should encourage close collaborations between biologists and computational linguists.     

The Gaggle: An open-source software system for integrating bioinformatics software and data sources

Background  

Systems biologists work with many kinds of data, from many different sources, using a variety of software tools. Each of these tools typically excels at one type of analysis, such as of microarrays, of metabolic networks and of predicted protein structure. A crucial challenge is to combine the capabilities of these (and other forthcoming) data resources and tools to create a data exploration and analysis environment that does justice to the variety and complexity of systems biology data sets. A solution to this problem should recognize that data types, formats and software in this high throughput age of biology are constantly changing.     

Open-source deep-learning software for bioimage segmentation

Microscopy images are rich in information about the dynamic relationships among biological structures. However, extracting this complex information can be challenging, especially when biological structures are closely packed, distinguished by texture rather than intensity, and/or low intensity relative to the background. By learning from large amounts of annotated data, deep learning can accomplish several previously intractable bioimage analysis tasks. Until the past few years, however, most deep-learning workflows required significant computational expertise to be applied. Here, we survey several new open-source software tools that aim to make deep-learning–based image segmentation accessible to biologists with limited computational experience. These tools take many different forms, such as web apps, plug-ins for existing imaging analysis software, and preconfigured interactive notebooks and pipelines. In addition to surveying these tools, we overview several challenges that remain in the field. We hope to expand awareness of the powerful deep-learning tools available to biologists for image analysis.     

BioMoby extensions to the Taverna workflow management and enactment software

Background  

As biology becomes an increasingly computational science, it is critical that we develop software tools that support not only bioinformaticians, but also bench biologists in their exploration of the vast and complex data-sets that continue to build from international genomic, proteomic, and systems-biology projects. The BioMoby interoperability system was created with the goal of facilitating the movement of data from one Web-based resource to another to fulfill the requirements of non-expert bioinformaticians. In parallel with the development of BioMoby, the European myGrid project was designing Taverna, a bioinformatics workflow design and enactment tool. Here we describe the marriage of these two projects in the form of a Taverna plug-in that provides access to many of BioMoby's features through the Taverna interface.     

Demystifying computer science for molecular ecologists

In this age of data‐driven science and high‐throughput biology, computational thinking is becoming an increasingly important skill for tackling both new and long‐standing biological questions. However, despite its obvious importance and conspicuous integration into many areas of biology, computer science is still viewed as an obscure field that has, thus far, permeated into only a few of the biology curricula across the nation. A national survey has shown that lack of computational literacy in environmental sciences is the norm rather than the exception [Valle & Berdanier (2012) Bulletin of the Ecological Society of America, 93, 373–389]. In this article, we seek to introduce a few important concepts in computer science with the aim of providing a context‐specific introduction aimed at research biologists. Our goal was to help biologists understand some of the most important mainstream computational concepts to better appreciate bioinformatics methods and trade‐offs that are not obvious to the uninitiated.     

BIRCH: A user-oriented,locally-customizable,bioinformatics system

Background  

Molecular biologists need sophisticated analytical tools which often demand extensive computational resources. While finding, installing, and using these tools can be challenging, pipelining data from one program to the next is particularly awkward, especially when using web-based programs. At the same time, system administrators tasked with maintaining these tools do not always appreciate the needs of research biologists.     

Computational Modeling,Formal Analysis,and Tools for Systems Biology

As the amount of biological data in the public domain grows, so does the range of modeling and analysis techniques employed in systems biology. In recent years, a number of theoretical computer science developments have enabled modeling methodology to keep pace. The growing interest in systems biology in executable models and their analysis has necessitated the borrowing of terms and methods from computer science, such as formal analysis, model checking, static analysis, and runtime verification. Here, we discuss the most important and exciting computational methods and tools currently available to systems biologists. We believe that a deeper understanding of the concepts and theory highlighted in this review will produce better software practice, improved investigation of complex biological processes, and even new ideas and better feedback into computer science.     

Genome annotation: which tools do we have for it?

Genome data have to be converted into knowledge to be useful to biologists. Many valuable computational tools have already been developed to help annotation of plant genome sequences, and these may be improved further, for example by identification of more gene regulatory elements. The lack of a standard computer-assisted annotation platform for eukaryotic genomes remains major bottle-neck.     

Extracting meaning from biological imaging data

Biological imaging continues to improve, capturing continually longer-term, richer, and more complex data, penetrating deeper into live tissue. How do we gain insight into the dynamic processes of disease and development from terabytes of multidimensional image data? Here I describe a collaborative approach to extracting meaning from biological imaging data. The collaboration consists of teams of biologists and engineers working together. Custom computational tools are built to best exploit application-specific knowledge in order to visualize and analyze large and complex data sets. The image data are summarized, extracting and modeling the features that capture the objects and relationships in the data. The summarization is validated, the results visualized, and errors corrected as needed. Finally, the customized analysis and visualization tools together with the image data and the summarization results are shared. This Perspective provides a brief guide to the mathematical ideas that rigorously quantify the notion of extracting meaning from biological image, and to the practical approaches that have been used to apply these ideas to a wide range of applications in cell and tissue optical imaging.     

Developmental biology: an array of new possibilities

Microarrays offer biologists comprehensive and powerful tools to analyze the involvement of genes in developmental processes at an unprecedented scale. Microarrays that employ defined sequences will permit us to elucidate genetic relationships and responses, while those that employ undefined DNA sequences (ESTs, cDNA, or genomic libraries) will help us to discover new genes, relate them to documented gene networks, and examine the way in which genes (and the process that they themselves control) are regulated. With access to broad new avenues of research come strategic and logistical headaches, most of which are embodied in the reams of data that are created over the course of an experiment. The solutions to these problems have provided interesting computational tools, which will allow us to compile huge data sets and to construct a genome-wide view of development. We are on the threshold of a new vista of possibilities where we might consider in comprehensive and yet specific detail, for example, the degree to which diverse organisms utilize similar genetic networks to achieve similar ends.     

Workflow management systems for gene sequence analysis and evolutionary studies – A Review

Post ‘omic’ era has resulted in the development of many primary, secondary and derived databases. Many analytical and visualization bioinformatics tools have been developed to manage and analyze the data available through large sequencing projects. Availability of heterogeneous databases and tools make it difficult for researchers to access information from varied sources and run different bioinformatics tools to get desired analysis done. Building integrated bioinformatics platforms is one of the most challenging tasks that bioinformatics community is facing. Integration of various databases, tools and algorithm is a challenging problem to deal with. This article describes the bioinformatics analysis workflow management systems that are developed in the area of gene sequence analysis and phylogeny. This article will be useful for biotechnologists, molecular biologists, computer scientists and statisticians engaged in computational biology and bioinformatics research.     

Performance comparison and evaluation of software tools for microRNA deep-sequencing data analysis

With the development of next-generation sequencing (NGS) techniques, many software tools have emerged for the discovery of novel microRNAs (miRNAs) and for analyzing the miRNAs expression profiles. An overall evaluation of these diverse software tools is lacking. In this study, we evaluated eight software tools based on their common feature and key algorithms. Three deep-sequencing data sets were collected from different species and used to assess the computational time, sensitivity and accuracy of detecting known miRNAs as well as their capacity for predicting novel miRNAs. Our results provide useful information for researchers to facilitate their selection of the optimal software tools for miRNA analysis depending on their specific requirements, i.e. novel miRNAs discovery or miRNA expression profile analysis of sequencing data sets.     

The Quantitative Methods Boot Camp: Teaching Quantitative Thinking and Computing Skills to Graduate Students in the Life Sciences

The past decade has seen a rapid increase in the ability of biologists to collect large amounts of data. It is therefore vital that research biologists acquire the necessary skills during their training to visualize, analyze, and interpret such data. To begin to meet this need, we have developed a “boot camp” in quantitative methods for biology graduate students at Harvard Medical School. The goal of this short, intensive course is to enable students to use computational tools to visualize and analyze data, to strengthen their computational thinking skills, and to simulate and thus extend their intuition about the behavior of complex biological systems. The boot camp teaches basic programming using biological examples from statistics, image processing, and data analysis. This integrative approach to teaching programming and quantitative reasoning motivates students’ engagement by demonstrating the relevance of these skills to their work in life science laboratories. Students also have the opportunity to analyze their own data or explore a topic of interest in more detail. The class is taught with a mixture of short lectures, Socratic discussion, and in-class exercises. Students spend approximately 40% of their class time working through both short and long problems. A high instructor-to-student ratio allows students to get assistance or additional challenges when needed, thus enhancing the experience for students at all levels of mastery. Data collected from end-of-course surveys from the last five offerings of the course (between 2012 and 2014) show that students report high learning gains and feel that the course prepares them for solving quantitative and computational problems they will encounter in their research. We outline our course here which, together with the course materials freely available online under a Creative Commons License, should help to facilitate similar efforts by others.This is part of the PLOS Computational Biology Education collection.     

Network thinking in ecology and evolution

Although pairwise interactions have always had a key role in ecology and evolutionary biology, the recent increase in the amount and availability of biological data has placed a new focus on the complex networks embedded in biological systems. The increased availability of computational tools to store and retrieve biological data has facilitated wide access to these data, not just by biologists but also by specialists from the social sciences, computer science, physics and mathematics. This fusion of interests has led to a burst of research on the properties and consequences of network structure in biological systems. Although traditional measures of network structure and function have started us off on the right foot, an important next step is to create biologically realistic models of network formation, evolution, and function. Here, we review recent applications of network thinking to the evolution of networks at the gene and protein level and to the dynamics and stability of communities. These studies have provided new insights into the organization and function of biological systems by applying existing techniques of network analysis. The current challenge is to recognize the commonalities in evolutionary and ecological applications of network thinking to create a predictive science of biological networks.     

Integrated prediction of the effect of mutations on multiple protein characteristics

Site-directed mutagenesis is routinely used in modern biology to elucidate the functional or biophysical roles of protein residues, and plays an important role in the field of rational protein design. Over the past decade, a number of computational tools have been developed that can predict the effect of point mutations on a protein's biophysical characteristics. However, these programs usually provide predictions for only a single characteristic. Furthermore, online versions of these tools are often impractical to use for examination of large and diverse sets of mutants. We have created a new web application, (http://enzyme.ucd.ie/PEAT_SA), that can simultaneously predict the effect of mutations on stability, ligand affinity and pK(a) values. PEAT-SA also provides an expanded feature-set with respect to other online tools which includes the ability to obtain predictions for multiple mutants in one submission. As a result, researchers who use site-directed mutagenesis can access state-of-the-art protein design methods with a fraction of the effort previously required. The results of benchmarking PEAT-SA on standard test-sets demonstrate that its accuracy for all three prediction types compares well to currently available tools. We illustrate PEAT-SA's potential by using it to investigate the influence of mutations on the activity of Subtilisin BPN'. This example demonstrates how the ability to obtain a wide range of information from one source, that can be combined to obtain deeper insight into the influence of mutations, makes PEAT-SA a valuable service to both experimental and computational biologists.     

Model building and model checking for biochemical processes

A central claim of computational systems biology is that, by drawing on mathematical approaches developed in the context of dynamic systems, kinetic analysis, computational theory and logic, it is possible to create powerful simulation, analysis, and reasoning tools for working biologists to decipher existing data, devise new experiments, and ultimately to understand functional properties of genomes, proteomes, cells, organs, and organisms. In this article, a novel computational tool is described that achieves many of the goals of this new discipline. The novelty of this system involves an automaton-based semantics of the temporal evolution of complex biochemical reactions starting from the representation given as a set of differential equations. The related tools also provide ability to qualitatively reason about the systems using a propositional temporal logic that can express an ordered sequence of events succinctly and unambiguously. The implementation of mathematical and computational models in the Simpathica and XSSYS systems is described briefly. Several example applications of these systems to cellular and biochemical processes are presented: the two most prominent are Leibler et al.'s repressilator (an artificial synthesized oscillatory network), and Curto-Voit-Sorribas-Cascante's purine metabolism reaction model.     

Automated data integration for developmental biological research

In an era exploding with genome-scale data, a major challenge for developmental biologists is how to extract significant clues from these publicly available data to benefit our studies of individual genes, and how to use them to improve our understanding of development at a systems level. Several studies have successfully demonstrated new approaches to classic developmental questions by computationally integrating various genome-wide data sets. Such computational approaches have shown great potential for facilitating research: instead of testing 20,000 genes, researchers might test 200 to the same effect. We discuss the nature and state of this art as it applies to developmental research.     

The Virtual Cell: a software environment for computational cell biology

The newly emerging field of computational cell biology requires software tools that address the needs of a broad community of scientists. Cell biological processes are controlled by an interacting set of biochemical and electrophysiological events that are distributed within complex cellular structures. Computational modeling is familiar to researchers in fields such as molecular structure, neurobiology and metabolic pathway engineering, and is rapidly emerging in the area of gene expression. Although some of these established modeling approaches can be adapted to address problems of interest to cell biologists, relatively few software development efforts have been directed at the field as a whole. The Virtual Cell is a computational environment designed for cell biologists as well as for mathematical biologists and bioengineers. It serves to aid the construction of cell biological models and the generation of simulations from them. The system enables the formulation of both compartmental and spatial models, the latter with either idealized or experimentally derived geometries of one, two or three dimensions.     

What You Should Know About Land-Cover Data

ABSTRACT Wildlife biologists are using land-characteristics data sets for a variety of applications. Many kinds of landscape variables have been characterized and the resultant data sets or maps are readily accessible. Often, too little consideration is given to the accuracy or traits of these data sets, most likely because biologists do not know how such data are compiled and rendered, or the potential pitfalls that can be encountered when applying these data. To increase understanding of the nature of land-characteristics data sets, I introduce aspects of source information and data-handling methodology that include the following: ambiguity of land characteristics; temporal considerations and the dynamic nature of the landscape; type of source data versus landscape features of interest; data resolution, scale, and geographic extent; data entry and positional problems; rare landscape features; and interpreter variation. I also include guidance for determining the quality of land-characteristics data sets through metadata or published documentation, visual clues, and independent information. The quality or suitability of the data sets for wildlife applications may be improved with thematic or spatial generalization, avoidance of transitional areas on maps, and merging of multiple data sources. Knowledge of the underlying challenges in compiling such data sets will help wildlife biologists to better assess the strengths and limitations and determine how best to use these data.