Charting plant gene functions in the multi-omics and single-cell era

Despite the increased access to high-quality plant genome sequences, the set of genes with a known function remains far from complete. With the advent of novel bulk and single-cell omics profiling methods, we are entering a new era where advanced and highly integrative functional annotation strategies are being developed to elucidate the functions of all plant genes. Here, we review different multi-omics approaches to improve functional and regulatory gene characterization and highlight the power of machine learning and network biology to fully exploit the complementary information embedded in different omics layers. Finally, we discuss the potential of emerging single-cell methods and algorithms to further increase the resolution, allowing generation of functional insights about plant biology.     

Advances in proteomic technologies and their scope of application in understanding plant–pathogen interactions

Proteomics, one of the major tools of ‘omics’ is evolving phenomenally since the development and application of two-dimensional gel electrophoresis coupled with mass spectrometry at the end of twentieth century. However, the adoption and application of advanced proteomic technologies in understanding plant–pathogen interactions are far less, when compared to their application in other related fields of systems biology. Hence, this review is diligently focused on the advances in various proteomic approaches and their gamut of applications in different facets of phyto-pathoproteomics. Especially, the scope and application of proteomics in understanding fundamental concepts of plant–pathogen interactions such as identification of pathogenicity determinants (effector proteins), disease resistance proteins (resistance and pathogenesis-related proteins) and their regulation by post-translational modifications have been portrayed. This review, for the first time, presents a critical appraisal of various proteomic applications by assessing all phyto-pathoproteomics-related research publications that were published in peer-reviewed journals, during the period 2000–2016. This assessment has revealed the present status and contribution of proteomic applications in different categories of phyto-pathoproteomics, namely, cellular components, host–pathogen interactions, model and non-model plants, and utilization of different proteomic approaches. Comprehensively, the analysis highlights the burgeoning application of global proteome approaches in various crop diseases, and demand for acceleration in deploying advanced proteomic technologies to thoroughly comprehend the intricacies of complex and rapidly evolving plant–pathogen interactions.     

Changing concepts of the pulmonary plexiform lesion

The plexiform lesion is the hallmark of plexogenic pulmonary arteriopathy, which accompanies severe primary pulmonary hypertension. Over the years, a wide variety of hypotheses have been offered to explain the pathogenesis of these glomoid structures. Most recently, the new techniques and concepts of molecular biology have been applied to the study of the plexiform lesion and have indicated that they are composed of phenotypically abnormal endothelial cells with different pathogenic origins in primary and secondary pulmonary hypertension. The new approaches and concepts have suggested new vistas for exploration.     

Targeting and tinkering with interaction networks

Biological interaction networks have been in the scientific limelight for nearly a decade. Increasingly, the concept of network biology and its various applications are becoming more commonplace in the community. Recent years have seen networks move from pretty pictures with limited application to solid concepts that are increasingly used to understand the fundamentals of biology. They are no longer merely results of postgenome analysis projects, but are now the starting point of many of the most exciting new scientific developments. We discuss here recent progress in identifying and understanding interaction networks, new tools that use them in predictive ways in exciting areas of biology, and how they have become the focus of many efforts to study, design and tinker with biological systems, with applications in biomedicine, bioengineering, ecology and beyond.     

Systems Biology in Aging: Linking the Old and the Young

Aging can be defined as a process of progressive decline in the physiological capacity of an organism, manifested by accumulated alteration and destabilization at the whole system level. Systems biology approaches offer a promising new perspective to examine the old problem of aging. We begin this review by introducing the concepts of systems biology, and then illustrate the application of systems biology approaches to aging research, from gene expression profiling to network analysis. We then introduce the network that can be constructed using known lifespan and aging regulators, and conclude with a look forward to the future of systems biology in aging research. In summary, systems biology is not only a young field that may help us understand aging at a higher level, but also an important platform that can link different levels of knowledge on aging, moving us closer to a more comprehensive control of systematic decline during aging.     

Pattern, process and the evolution of meaning: species and units of selection

Many of the fundamental concepts of biology lack consensual, precise definitions. Partly, this is due to a contrast between our discrete language and the continuous character of nature. Some debates over these concepts are confounded by the use of the same terms with different specific meanings, indicating a possible need for an expanded scientific lexicon. Words have their own histories, and frequently scientific terms with a vernacular origin retain associated vestigial meanings. Even terms newly coined within science have histories and changing meanings, which can lead to confusion among debaters. Debates over concepts are further confounded when the same terms are used in different fields of biology, with distinct (even conflicting) objectives, and by biologists with different approaches and perspectives. I illustrate these issues by considering the debate over the concept of species and the unit of selection.     

IMGT, a system and an ontology that bridge biological and computational spheres in bioinformatics

IMGT, the international ImMunoGeneTics information system (http://imgt.cines.fr), is the reference in immunogenetics and immunoinformatics. IMGT standardizes and manages the complex immunogenetic data that include the immunoglobulins (IG) or antibodies, the T cell receptors (TR), the major histocompatibility complex (MHC) and the related proteins of the immune system (RPI), which belong to the immunoglobulin superfamily (IgSF) and the MHC superfamily (MhcSF). The accuracy and consistency of IMGT data and the coherence between the different IMGT components (databases, tools and Web resources) are based on IMGT-ONTOLOGY, the first ontology for immunogenetics and immunoinformatics. IMGT-ONTOLOGY manages the immunogenetics knowledge through diverse facets relying on seven axioms, 'IDENTIFICATION', 'DESCRIPTION', 'CLASSIFICATION', 'NUMEROTATION', 'LOCALIZATION', 'ORIENTATION' and 'OBTENTION', that postulate that objects, processes and relations have to be identified, described, classified, numerotated, localized, orientated, and that the way they are obtained has to be determined. These axioms constitute the Formal IMGT-ONTOLOGY, also designated as IMGT-Kaleidoscope. These axioms have been essential for the conceptualization of the molecular immunogenetics knowledge and for the creation of IMGT. Indeed all the components of the IMGT integrated system have been developed, based on standardized concepts and relations, thus allowing IMGT to bridge biological and computational spheres in bioinformatics. The same axioms can be used to generate concepts for multi-scale level approaches at the molecule, cell, tissue, organ, organism or population level, emphasizing the generalization of the application domain. In that way the Formal IMGT-ONTOLOGY represents a paradigm for the elaboration of ontologies in system biology.     

Tuning specificity and topology of lectins through synthetic biology

Lectins are non-immunoglobulin and non-catalytic glycan binding proteins that are able to decipher the structure and function of complex glycans. They are widely used as biomarkers for following alteration of glycosylation state in many diseases and have application in therapeutics. Controlling and extending lectin specificity and topology is the key for obtaining better tools. Furthermore, lectins and other glycan binding proteins can be combined with additional domains, providing novel functionalities. We provide a view on the current strategy with a focus on synthetic biology approaches yielding to novel specificity, but other novel architectures with novel application in biotechnology or therapy.     

IMGT-Kaleidoscope, the formal IMGT-ONTOLOGY paradigm

IMGT, the international ImMunoGeneTics information system (http://imgt.cines.fr), is the reference in immunogenetics and immunoinformatics. IMGT standardizes and manages the complex immunogenetic data which include the immunoglobulins (IG) or antibodies, the T cell receptors (TR), the major histocompatibility complex (MHC) and the related proteins of the immune system (RPI) which belong to the immunoglobulin superfamily (IgSF) and the MHC superfamily (MhcSF). The accuracy and consistency of IMGT data and the coherence between the different IMGT components (databases, tools and Web resources) are based on IMGT-ONTOLOGY, the first ontology for immunogenetics and immunoinformatics. IMGT-ONTOLOGY manages the immunogenetics knowledge through diverse facets relying on seven axioms, "IDENTIFICATION", "DESCRIPTION", "CLASSIFICATION", "NUMEROTATION", "LOCALIZATION", "ORIENTATION" and "OBTENTION", that postulate that objects, processes and relations have to be identified, described, classified, numerotated, localized, orientated, and that the way they are obtained has to be determined. These axioms constitute the Formal IMGT-ONTOLOGY, also designated as IMGT-Kaleidoscope. Through the example of the IG molecular synthesis, the concepts generated from the "IDENTIFICATION", "DESCRIPTION", "CLASSIFICATION" and "NUMEROTATION" axioms are detailed with their main instances and semantic relations. The axioms have been essential for the conceptualization of the molecular immunogenetics knowledge and can be used to generate concepts for multi scale approaches at the molecule, cell, tissue, organ, organism or population level, emphasizing the generalization of the application domain. In that way the Formal IMGT-ONTOLOGY represents a paradigm for the elaboration of ontologies in system biology.     

Engineering and control of biological systems: A new way to tackle complex diseases

The ongoing merge between engineering and biology has contributed to the emerging field of synthetic biology. The defining features of this new discipline are abstraction and standardisation of biological parts, decoupling between parts to prevent undesired cross-talking, and the application of quantitative modelling of synthetic genetic circuits in order to guide their design. Most of the efforts in the field of synthetic biology in the last decade have been devoted to the design and development of functional gene circuits in prokaryotes and unicellular eukaryotes. Researchers have used synthetic biology not only to engineer new functions in the cell, but also to build simpler models of endogenous gene regulatory networks to gain knowledge of the "rules" governing their wiring diagram. However, the need for innovative approaches to study and modify complex signalling and regulatory networks in mammalian cells and multicellular organisms has prompted advances of synthetic biology also in these species, thus contributing to develop innovative ways to tackle human diseases. In this work, we will review the latest progress in synthetic biology and the most significant developments achieved so far, both in unicellular and multicellular organisms, with emphasis on human health.     

活细胞单分子实时视见研究

我们对细胞生物学与分子生物学中有关分子事件和相互作用的认识,大部分都是集团平均水平研究的结果,并且基于所有的分子在给定时间内以完全相同的方式运动这样一种不真实的假设。现在,激光技术和全内反射显微镜的应用,以及绿色荧光蛋白(green fluorescent proteins,GFPs)等新的分子荧光探针的出现,使得显示活细胞单个生物分子的运动行为和轨迹成为可能。单分子水平的研究将会加深人们对分子和细胞生物学的基本概念的认识。     

A federated design for a neurobiological simulation engine: the CBI federated software architecture

Simulator interoperability and extensibility has become a growing requirement in computational biology. To address this, we have developed a federated software architecture. It is federated by its union of independent disparate systems under a single cohesive view, provides interoperability through its capability to communicate, execute programs, or transfer data among different independent applications, and supports extensibility by enabling simulator expansion or enhancement without the need for major changes to system infrastructure. Historically, simulator interoperability has relied on development of declarative markup languages such as the neuron modeling language NeuroML, while simulator extension typically occurred through modification of existing functionality. The software architecture we describe here allows for both these approaches. However, it is designed to support alternative paradigms of interoperability and extensibility through the provision of logical relationships and defined application programming interfaces. They allow any appropriately configured component or software application to be incorporated into a simulator. The architecture defines independent functional modules that run stand-alone. They are arranged in logical layers that naturally correspond to the occurrence of high-level data (biological concepts) versus low-level data (numerical values) and distinguish data from control functions. The modular nature of the architecture and its independence from a given technology facilitates communication about similar concepts and functions for both users and developers. It provides several advantages for multiple independent contributions to software development. Importantly, these include: (1) Reduction in complexity of individual simulator components when compared to the complexity of a complete simulator, (2) Documentation of individual components in terms of their inputs and outputs, (3) Easy removal or replacement of unnecessary or obsoleted components, (4) Stand-alone testing of components, and (5) Clear delineation of the development scope of new components.     

Molecular biology in physiology

The aim of this symposium on molecular biology in physiology was to introduce molecular biology to physiologists who had relatively little exposure to the new developments in this field, so that they can become conversant on this topic and contribute to the advancement of physiology by incorporating molecular biological approaches as a part of their research arsenal. After the discussion of the basic concepts, terminology, and methodology used in molecular biology, it was shown how these basic principles have been applied to the study of the genes encoding two membrane proteins that have important transport functions (band 3 and ATPase). The second half of the symposium consisted of papers on the state-of-the-art developments in the application of molecular biology to the studies of the atrial natriuretic factor and renin genes, adenylate cyclase-coupled adrenergic receptors, acetylcholine receptors and sodium channel, and long-term and short-term memories. The ultimate goal is that these examples will provide an impetus for the opening of new frontiers of research in physiology by taking advantage of the tools developed from recent advances in molecular biology.     

Magnetic tweezers: a sensitive tool to study DNA and chromatin at the single-molecule level.

The advent of single-molecule biology has allowed unprecedented insight into the dynamic behavior of biological macromolecules and their complexes. Unexpected properties, masked by the asynchronous behavior of myriads of molecules in bulk experiments, can be revealed; equally importantly, individual members of a molecular population often exhibit distinct features in their properties. Finally, the single-molecule approaches allow us to study the behavior of biological macromolecules under applied tension or torsion; understanding the mechanical properties of these molecules helps us understand how they function in the cell. In this review, we summarize the application of magnetic tweezers (MT) to the study of DNA behavior at the single-molecule level. MT can be conveniently used to stretch DNA and introduce controlled levels of superhelicity into the molecule and to follow to a high definition the action of different types of topoisomerases. Its potential for chromatin studies is also enormous, and we will briefly present our first chromatin results.     

Mining literature for systems biology

Currently, literature is integrated in systems biology studies in three ways. Hand-curated pathways have been sufficient for assembling models in numerous studies. Second, literature is frequently accessed in a derived form, such as the concepts represented by the Medical Subject Headings (MeSH) and Gene Ontologies (GO), or functional relationships captured in protein-protein interaction (PPI) databases; both of these are convenient, consistent reductions of more complex concepts expressed as free text in the literature. Moreover, their contents are easily integrated into computational processes required for dealing with large data sets. Last, mining text directly for specific types of information is on the rise as text analytics methods become more accurate and accessible. These uses of literature, specifically manual curation, derived concepts captured in ontologies and databases, and indirect and direct application of text mining, will be discussed as they pertain to systems biology.     

Recent application of metagenomic approaches toward the discovery of antimicrobials and other bioactive small molecules

Bacteria grown in pure culture have been the starting point for the discovery of many of the antibacterials now in use. Metagenomics, which utilizes culture-independent methods to access the collective genomes of natural bacterial populations, provides a means of exploring the antimicrobials produced by the large collections of bacteria that are known to be present in the environment but remain recalcitrant to culturing. Both novel small molecule antibiotics and new antibacterially active proteins have been identified using metagenomic approaches. The recent application of metagenomics to the discovery of bioactive small molecules, small molecule biosynthetic gene clusters and antibacterially active enzymes is discussed here.