Novel comprehensive approach for accessible biomarker identification and absolute quantification from precious human tissues

The identification of specific biomarkers obtained directly from human pathological lesions remains a major challenge, because the amount of tissue available is often very limited. We have developed a novel, comprehensive, and efficient method permitting the identification and absolute quantification of potentially accessible proteins in such precious samples. This protein subclass comprises cell membrane associated and extracellular proteins, which are reachable by systemically deliverable substances and hence especially suitable for diagnosis and targeted therapy applications. To isolate such proteins, we exploited the ability of chemically modified biotin to label ex vivo accessible proteins and the fact that most of these proteins are glycosylated. This approach consists of three successive steps involving first the linkage of potentially accessible proteins to biotin molecules followed by their purification. The remaining proteins are then subjected to glycopeptide isolation. Finally, the analysis of the nonglycosylated peptides and their involvement in an in silico method increased the confident identification of glycoproteins. The value of the technique was demonstrated on human breast cancer tissue samples originating from 5 individuals. Altogether, the method delivered quantitative data on more than 400 potentially accessible proteins (per sample and replicate). In comparison to biotinylation or glycoprotein analysis alone, the sequential method significantly increased the number (≥30% and ≥50% respectively) of potentially therapeutically and diagnostically valuable proteins. The sequential method led to the identification of 93 differentially modulated proteins, among which several were not reported to be associated with the breast cancer. One of these novel potential biomarkers was CD276, a cell membrane-associated glycoprotein. The immunohistochemistry analysis showed that CD276 is significantly differentially expressed in a series of breast cancer lesions. Due to the fact that our technology is applicable to any type of tissue biopsy, it bears the ability to accelerate the discovery of new relevant biomarkers in a broad spectrum of pathologies.     

斑马鱼在生命科学研究中的应用

利用模式生物进行研究是推动生命科学发展的主要手段之一.斑马鱼已成为继小鼠之后的又一个重要的模式脊椎动物.本文将重点介绍斑马鱼在学习记忆和疾病研究领域中的应用,以及我国推动斑马鱼相关研究的策略.     

Anni 2.0: a multipurpose text-mining tool for the life sciences

Anni 2.0 is an online tool () to aid the biomedical researcher with a broad range of information needs. Anni provides an ontology-based interface to MEDLINE and retrieves documents and associations for several classes of biomedical concepts, including genes, drugs and diseases, with established text-mining technology. In this article we illustrate Anni's usability by applying the tool to two use cases: interpretation of a set of differentially expressed genes, and literature-based knowledge discovery.     

Melatonin: perspectives in the life sciences

The pineal gland hormone melatonin is now considered an important neuroendocrine component of animal physiology. Although the functional status of melatonin has been well described for subhuman species, there is a paucity of data concerning the physiological role of this hormone in man. This paucity of data has much to do with the limitations of experimental design imposed by the practical and ethical difficulties associated with the study of a nocturnally secreted hormone. The recent advent of salivary melatonin assay has provided a very practical means of monitoring melatonin secretion in long-term longitudinal type community based studies of pineal gland function in human health and disease. The efforts to describe key chronobiological changes in melatonin secretion of possible functional significance have been accompanied by a seemingly less enthusiastic search to describe the nature of the melatonin receptor, another highly important component of the 'melatonin message'. The functional relevance of specific chronobiological changes in melatonin secretion cannot be completely understood without an increased knowledge of melatonin action at the receptor level. The present work describes the recent methodological advance in the investigation of human pineal gland physiology represented by salivary melatonin assay, and discusses the present status of our knowledge of the melatonin receptor.     

绿色荧光蛋白——照亮生命科学的一盏明灯

绿色荧光蛋白的发现及应用具有划时代的重要意义,它不仅为当代生物学研究提供了极为实用的基本研究手段,并且在此基础上改造发展和发现了一系列荧光蛋白,拓展了应用范围。这使得对微观生物学的研究也可以进入一个时空结合,研究鲜活动态过程的新时代。本文主要回顾总结了绿色荧光蛋白的发现、优化改造及其应用。     

微卫星不稳定性的生物学意义及其应用前景

微卫星为遍布于人类基因组中的简单重复序列。在人群中,它们呈现高度多态性,并且稳定遗传。微卫星的高度多态性是微卫星不稳定性的表现,它与错配修复基因的缺陷有关。微卫星不稳定性已广泛应用于肿瘤学的研究,并依此提出了肿瘤发生的“增变基因”途径。     

dCLIP: a computational approach for comparative CLIP-seq analyses

Although comparison of RNA-protein interaction profiles across different conditions has become increasingly important to understanding the function of RNA-binding proteins (RBPs), few computational approaches have been developed for quantitative comparison of CLIP-seq datasets. Here, we present an easy-to-use command line tool, dCLIP, for quantitative CLIP-seq comparative analysis. The two-stage method implemented in dCLIP, including a modified MA normalization method and a hidden Markov model, is shown to be able to effectively identify differential binding regions of RBPs in four CLIP-seq datasets, generated by HITS-CLIP, iCLIP and PAR-CLIP protocols. dCLIP is freely available at http://qbrc.swmed.edu/software/.     

从科研论文量看世界生命科学的发展

应用美国ESI基本科学指标数据库,对1993年至2003年世界科研产出成果进行统计分析,反映国内外生命科学重点研究领域和学科分布特点,揭示我国与国外相比存在的差距。从文献计量学角度,对我国生命科学的发展提出了建设性意见。     

Inquiry-based undergraduate teaching in the life sciences at large research universities: a perspective on the Boyer Commission Report

The 1998 Boyer Commission Report advocated improvement of undergraduate education at large research universities through large-scale participation of undergraduates in the universities' research mission. At a recent conference sponsored by the Reinvention Center, which is dedicated to furthering the goals of the Boyer Commission, participants discussed progress toward these goals and recommendations for future action. A breakout group representing the life sciences concluded that independent research experience for every undergraduate may not be feasible or desirable but that transformation of lecture courses to more inquiry-based and interactive formats can effectively further the Commission's goals.     

Opportunities and challenges for the life sciences community

Twenty-first century life sciences have transformed into data-enabled (also called data-intensive, data-driven, or big data) sciences. They principally depend on data-, computation-, and instrumentation-intensive approaches to seek comprehensive understanding of complex biological processes and systems (e.g., ecosystems, complex diseases, environmental, and health challenges). Federal agencies including the National Science Foundation (NSF) have played and continue to play an exceptional leadership role by innovatively addressing the challenges of data-enabled life sciences. Yet even more is required not only to keep up with the current developments, but also to pro-actively enable future research needs. Straightforward access to data, computing, and analysis resources will enable true democratization of research competitions; thus investigators will compete based on the merits and broader impact of their ideas and approaches rather than on the scale of their institutional resources. This is the Final Report for Data-Intensive Science Workshops DISW1 and DISW2. The first NSF-funded Data Intensive Science Workshop (DISW1, Seattle, WA, September 19-20, 2010) overviewed the status of the data-enabled life sciences and identified their challenges and opportunities. This served as a baseline for the second NSF-funded DIS workshop (DISW2, Washington, DC, May 16-17, 2011). Based on the findings of DISW2 the following overarching recommendation to the NSF was proposed: establish a community alliance to be the voice and framework of the data-enabled life sciences. After this Final Report was finished, Data-Enabled Life Sciences Alliance (DELSA, www.delsall.org ) was formed to become a Digital Commons for the life sciences community.     

Social tagging in the life sciences: characterizing a new metadata resource for bioinformatics

Background  

Academic social tagging systems, such as Connotea and CiteULike, provide researchers with a means to organize personal collections of online references with keywords (tags) and to share these collections with others. One of the side-effects of the operation of these systems is the generation of large, publicly accessible metadata repositories describing the resources in the collections. In light of the well-known expansion of information in the life sciences and the need for metadata to enhance its value, these repositories present a potentially valuable new resource for application developers. Here we characterize the current contents of two scientifically relevant metadata repositories created through social tagging. This investigation helps to establish how such socially constructed metadata might be used as it stands currently and to suggest ways that new social tagging systems might be designed that would yield better aggregate products.     

Systems microscopy: An emerging strategy for the life sciences

Dynamic cellular processes occurring in time and space are fundamental to all physiology and disease. To understand complex and dynamic cellular processes therefore demands the capacity to record and integrate quantitative multiparametric data from the four spatiotemporal dimensions within which living cells self-organize, and to subsequently use these data for the mathematical modeling of cellular systems. To this end, a raft of complementary developments in automated fluorescence microscopy, cell microarray platforms, quantitative image analysis and data mining, combined with multivariate statistics and computational modeling, now coalesce to produce a new research strategy, “systems microscopy”, which facilitates systems biology analyses of living cells. Systems microscopy provides the crucial capacities to simultaneously extract and interrogate multiparametric quantitative data at resolution levels ranging from the molecular to the cellular, thereby elucidating a more comprehensive and richly integrated understanding of complex and dynamic cellular systems. The unique capacities of systems microscopy suggest that it will become a vital cornerstone of systems biology, and here we describe the current status and future prospects of this emerging field, as well as outlining some of the key challenges that remain to be overcome.