Cell biology, chemogenomics and chemoproteomics

The scientific techniques used in molecular biological research and drug discovery have changed dramatically over the past 10 years due to the influence of genomics, proteomics and bioinformatics. Furthermore, genomics and functional genomics are now merging into a new scientific approach called chemogenomics. Advancements in the study of molecular cell biology are dependent upon "omics" researchers realizing the importance of and using the experimental tools currently available to cell biologists. For example, novel microscopic techniques utilizing advanced computer imaging allow for the examination of live specimens in a fourth dimension, viz., time. Yet, molecular biologists have not taken full advantage of these and other traditional and novel cell biology techniques for the further advancement of genomic and proteomic-oriented research. The application of traditional and novel cellular biological techniques will enhance the science of genomics. The authors hypothesize that a stronger interdisciplinary approach must be taken between cell biology (and its closely related fields) and genomics, proteomics and bio-chemoinformatics. Since there is a lot of confusion regarding many of the "omics" definitions, this article also clarifies some of the basic terminology used in genomics, and related fields. It also reviews the current status and future potential of chemogenomics and its relationship to cell biology. The authors also discuss and expand upon the differences between chemogenomics and the relatively new term--chemoproteomics. We conclude that the advances in cell biology methods and approaches and their adoption by "omics" researchers will allow scientists to maximize our knowledge about life.     

Advances in ionisation techniques for mass spectrometry-based omics research

Omics analysis by mass spectrometry (MS) is a vast field, with proteomics, metabolomics and lipidomics dominating recent research by exploiting biological MS ionisation techniques. Traditional MS ionisation techniques such as electrospray ionisation have limitations in analyte-specific sensitivity, modes of sampling and throughput, leading to many researchers investigating new ionisation methods for omics research. In this review, we examine the current landscape of these new ionisation techniques, divided into the three groups of (electro)spray-based, laser-based and other miscellaneous ionisation techniques. Due to the wide range of new developments, this review can only provide a starting point for further reading on each ionisation technique, as each have unique benefits, often for specialised applications, which promise beneficial results for different areas in the omics world.     

Novel physical chemistry approaches in biophysical researches with advanced application of lasers: Detection and manipulation

Novel methodologies utilizing pulsed or intense CW irradiation obtained from lasers have a major impact on biological sciences. In this article, recent development in biophysical researches fully utilizing the laser irradiation is described for three topics, time-resolved fluorescence spectroscopy, time-resolved thermodynamics, and manipulation of the biological assemblies by intense laser irradiation. First, experimental techniques for time-resolved fluorescence spectroscopy are concisely explained in Section 2. As an example of the recent application of time-resolved fluorescence spectroscopy to biological systems, evaluation of the viscosity of lipid bilayer membranes is described. The results of the spectroscopic experiments strongly suggest the presence of heterogeneous membrane structure with two different viscosity values in liposomes formed by a single phospholipid. Section 3 covers the time-resolved thermodynamics. Thermodynamical properties are important to characterize biomolecules. However, measurement of these quantities for short-lived intermediate species has been impossible by traditional thermodynamical techniques. Recently, development of a spectroscopic method based on the transient grating method enables us to measure these quantities and also to elucidate reaction kinetics which cannot be detected by other spectroscopic methods. The principle of the measurements and applications to some protein reactions are reviewed. Manipulation and fabrication of supramolecues, amino acids, proteins, and living cells by intense laser irradiation are described in Section 4. Unconventional assembly, crystallization and growth, amyloid fibril formation, and living cell manipulation are achieved by CW laser trapping and femtosecond laser-induced cavitation bubbling. Their spatio-temporal controllability is opening a new avenue in the relevant molecular and bioscience research fields. This article is part of a Special Issue entitled “Biophysical Exploration of Dynamical Ordering of Biomolecular Systems” edited by Dr. Koichi Kato.     

Data integration in the era of omics: current and future challenges

To integrate heterogeneous and large omics data constitutes not only a conceptual challenge but a practical hurdle in the daily analysis of omics data. With the rise of novel omics technologies and through large-scale consortia projects, biological systems are being further investigated at an unprecedented scale generating heterogeneous and often large data sets. These data-sets encourage researchers to develop novel data integration methodologies. In this introduction we review the definition and characterize current efforts on data integration in the life sciences. We have used a web-survey to assess current research projects on data-integration to tap into the views, needs and challenges as currently perceived by parts of the research community.     

系统生物学研究中不同组学数据的整合

高通量实验方法的发展导致大量基因组、转录组、代谢组等组学数据的出现,组学数据的整合为全面了解生物学系统提供了条件.但是,由于当前实验技术手段的限制,高通量组学数据大多存在系统偏差,数据类型和可靠程度也各不相同,这给组学数据的整合带来了困难.本文以转录组、蛋白质组和代谢组为重点,综述了近年来组学数据整合方面的研究进展,包括新的数据整合方法和分析平台.虽然现存的数据统计和网络分析的方法有助于发现不同组学数据之间的关联,但是生物学意义上的深层次的数据整合还有待于生物、数学、计算机等各种领域的全面发展.     

Surface analysis of lipids by mass spectrometry: More than just imaging

Mass spectrometry is now an indispensable tool for lipid analysis and is arguably the driving force in the renaissance of lipid research. In its various forms, mass spectrometry is uniquely capable of resolving the extensive compositional and structural diversity of lipids in biological systems. Furthermore, it provides the ability to accurately quantify molecular-level changes in lipid populations associated with changes in metabolism and environment; bringing lipid science to the “omics” age. The recent explosion of mass spectrometry-based surface analysis techniques is fuelling further expansion of the lipidomics field. This is evidenced by the numerous papers published on the subject of mass spectrometric imaging of lipids in recent years. While imaging mass spectrometry provides new and exciting possibilities, it is but one of the many opportunities direct surface analysis offers the lipid researcher. In this review we describe the current state-of-the-art in the direct surface analysis of lipids with a focus on tissue sections, intact cells and thin-layer chromatography substrates. The suitability of these different approaches towards analysis of the major lipid classes along with their current and potential applications in the field of lipid analysis are evaluated.     

Integration of omics data: how well does it work for bacteria?

In the current omics era, innovative high-throughput technologies allow measuring temporal and conditional changes at various cellular levels. Although individual analysis of each of these omics data undoubtedly results into interesting findings, it is only by integrating them that gaining a global insight into cellular behaviour can be aimed at. A systems approach thus is predicated on data integration. However, because of the complexity of biological systems and the specificities of the data-generating technologies (noisiness, heterogeneity, etc.), integrating omics data in an attempt to reconstruct signalling networks is not trivial. Developing its methodologies constitutes a major research challenge. Besides for their intrinsic value towards health care, environment and industry, prokaryotes are ideal model systems to further develop these methods because of their lower regulatory complexity compared with eukaryotes, and the ease with which they can be manipulated. Several successful examples outlined in this review already show the potential of the systems approach for both fundamental and industrial applications, which would be time-consuming or impossible to develop solely through traditional reductionist approaches.     

New techniques in fast time-resolved structure determination.

New techniques in fast time-resolved X-ray crystallography provide a different approach to understanding the structural basis of protein function. Two biological systems have been studied as part of the refinement of these techniques, and have actually spurred new ideas in time-resolved structural studies. The dissociation of carbon monoxide from carbon-monoxy myoglobin has earlier been investigated over a time range spanning 18 orders of magnitude (femtoseconds to hours) using spectroscopic methods. Rapid time-resolved determination of the entire myoglobin structure made it possible to determine both the position of the CO after photodissociation and the entire globin structure, over a time range from nanoseconds to milliseconds, during which the heme and globin relax and the carbon monoxide rebinds. Photoactive yellow protein, a relative newcomer to biophysical research, has a fully-reversible photocycle containing several spectrally distinct intermediates. Identifying and solving the structures of each intermediate is the initial goal in time-resolved studies on this protein and will contribute to a greater understanding of the biological process of light driven signal transduction.     

Information engineering infrastructure for life sciences and its implementation in China

Biological data,represented by the data from omics platforms,are accumulating exponentially.As some other data-intensive scientific disciplines such as high-energy physics,climatology,meteorology,geology,geography and environmental sciences,modern life sciences have entered the information-rich era,the era of the 4th paradigm.The creation of Chinese information engineering infrastructure for pan-omics studies(CIEIPOS) has been long overdue as part of national scientific infrastructure,in accelerating the further development of Chinese life sciences,and translating rich data into knowledge and medical applications.By gathering facts of current status of international and Chinese bioinformatics communities in collecting,managing and utilizing biological data,the essay stresses the significance and urgency to create a ’data hub’ in CIEIPOS,discusses challenges and possible solutions to integrate,query and visualize these data.Another important component of CIEIPOS,which is not part of traditional biological data centers such as NCBI and EBI,is omics informatics.Mass spectroscopy platform was taken as an example to illustrate the complexity of omics informatics.Its heavy dependency on computational power is highlighted.The demand for such power in omics studies is argued as the fundamental function to meet for CIEIPOS.Implementation outlook of CIEIPOS in hardware and network is discussed.     

系统生物学视野下的功能氨基酸组学

传统营养学将氨基酸作为蛋白质的构建单元来研究蛋白质和氨基酸。近年来的研究表明,氨基酸在物质代谢和免疫功能调控等方面亦发挥重要作用,并提出功能性氨基酸的概念。随着各种组学技术的不断发展,通过系统生物学的理念与方法整合组学数据,系统地分析功能氨基酸的分子作用机制、药效学、体内动态过程成为可能。为此,本文提出功能氨基酸组学的概念,指出功能氨基酸组学领域的科学问题,提出功能氨基酸组学的研究内容。研究结果可用于朝向特定目标的氨基酸组合设计。     

Advances in omics and bioinformatics tools for systems analyses of plant functions

Omics and bioinformatics are essential to understanding the molecular systems that underlie various plant functions. Recent game-changing sequencing technologies have revitalized sequencing approaches in genomics and have produced opportunities for various emerging analytical applications. Driven by technological advances, several new omics layers such as the interactome, epigenome and hormonome have emerged. Furthermore, in several plant species, the development of omics resources has progressed to address particular biological properties of individual species. Integration of knowledge from omics-based research is an emerging issue as researchers seek to identify significance, gain biological insights and promote translational research. From these perspectives, we provide this review of the emerging aspects of plant systems research based on omics and bioinformatics analyses together with their associated resources and technological advances.     

From observational to actionable: rethinking omics in biologics production

As the era of omics continues to expand with increasing ubiquity and success in both academia and industry, omics-based experiments are becoming commonplace in industrial biotechnology, including efforts to develop novel solutions in bioprocess optimization and cell line development. Omic technologies provide particularly valuable ‘observational’ insights for discovery science, especially in academic research and industrial R&D; however, biomanufacturing requires a different paradigm to unlock ‘actionable’ insights from omics. Here, we argue the value of omic experiments in biotechnology can be maximized with deliberate selection of omic approaches and forethought about analysis techniques. We describe important considerations when designing and implementing omic-based experiments and discuss how systems biology analysis strategies can enhance efforts to obtain actionable insights in mammalian-based biologics production.     

Interpretation of network-based integration from multi-omics longitudinal data

Multi-omics integration is key to fully understand complex biological processes in an holistic manner. Furthermore, multi-omics combined with new longitudinal experimental design can unreveal dynamic relationships between omics layers and identify key players or interactions in system development or complex phenotypes. However, integration methods have to address various experimental designs and do not guarantee interpretable biological results. The new challenge of multi-omics integration is to solve interpretation and unlock the hidden knowledge within the multi-omics data. In this paper, we go beyond integration and propose a generic approach to face the interpretation problem. From multi-omics longitudinal data, this approach builds and explores hybrid multi-omics networks composed of both inferred and known relationships within and between omics layers. With smart node labelling and propagation analysis, this approach predicts regulation mechanisms and multi-omics functional modules. We applied the method on 3 case studies with various multi-omics designs and identified new multi-layer interactions involved in key biological functions that could not be revealed with single omics analysis. Moreover, we highlighted interplay in the kinetics that could help identify novel biological mechanisms. This method is available as an R package netOmics to readily suit any application.     

Proteins in action: the physics of structural fluctuations and conformational changes

Structural dynamics is essential for the biological function of proteins. Results from new experimental techniques should be compared with those from previous experiments in order to obtain a consistent picture of the physics of intramolecular fluctuations and conformational changes. The high intensity and time structure of synchrotron radiation have made possible time-resolved X-ray structure analysis and the determination of phonon density spectra through the M?ssbauer effect. By combining results from M?ssbauer absorption spectroscopy, incoherent neutron scattering, low-temperature crystallography and optical spectroscopy, a physical picture of protein dynamics emerges.     

Role of nuclear analytical probe techniques in biological trace-element research

Many biomedical experiments require the qualitative and quantitative localization of trace elements with high sensitivity and good spatial resolution. The feasibility of measuring the chemical form of the elements, the time course of trace element metabolism, and conducting experiments in living biological systems are also important requirements for biological trace element research. Nuclear analytical techniques that employ ion or photon beams have grown in importance in the past decade and have led to several new experimental approaches. Some of the important features of these methods are reviewed here along with their role in trace element research. Examples of their use are given to illustrate potential for new research directions. It is emphasized that the effective application of these methods necessitates a closely integrated multidisciplinary scientific team.