Moss systems biology en route: phytohormones in Physcomitrella development

The moss Physcomitrella patens has become a powerful model system in modern plant biology. Highly standardized cell culture techniques, as well as the necessary tools for computational biology, functional genomics and proteomics have been established. Large EST collections are available and the complete moss genome will be released soon. A simple body plan and the small number of different cell types in Physcomitrella facilitate the study of developmental processes. In the filamentous juvenile moss tissue, developmental decisions rely on the differentiation of single cells. Developmental steps are controlled by distinct phytohormones and integration of environmental signals. Especially the phytohormones auxin, cytokinin, and abscisic acid have distinct effects on early moss development. In this article, we review current knowledge about phytohormone influences on early moss development in an attempt to fully unravel the complex regulatory signal transduction networks underlying the developmental decisions of single plant cells in a holistic systems biology approach.     

Applications of integrative OMICs approaches to gene regulation studies

Background: Functional genomics employs dozens of OMICs technologies to explore the functions of DNA, RNA and protein regulators in gene regulation processes. Despite each of these technologies being powerful tools on their own, like the parable of blind men and an elephant, any one single technology has a limited ability to depict the complex regulatory system. Integrative OMICS approaches have emerged and become an important area in biology and medicine. It provides a precise and effective way to study gene regulations.Results: This article reviews current popular OMICs technologies, OMICs data integration strategies, and bioinformatics tools used for multi-dimensional data integration. We highlight the advantages of these methods, particularly in elucidating molecular basis of biological regulatory mechanisms. Conclusions: To better understand the complexity of biological processes, we need powerful bioinformatics tools to integrate these OMICs data. Integrating multi-dimensional OMICs data will generate novel insights into system-level gene regulations and serves as a foundation for further hypothesis-driven research.     

面向药物发现和精准医疗的基因表达谱分析

作为功能基因组学中重要的组成部分,基因表达谱在生物学、医学和药物研发等多个领域发挥着重要作用.特别是随着精准医疗概念的提出,整合多组学数据用于个性化医疗是未来的发展趋势.本文从基因表达谱的基本概念出发,重点介绍面向药物发现的基因表达谱分析方法,即基于关联图谱的方法、基于基因调控网络的方法和基于多组学数据整合的方法.系统整理了各种方法的研究进展,特别是在抗癌药物研发领域的最新进展,为利用基因表达谱数据进行药物研发提供方法借鉴.     

The pig genome project has plenty to squeal about

Significant progress on pig genetics and genomics research has been witnessed in recent years due to the integration of advanced molecular biology techniques, bioinformatics and computational biology, and the collaborative efforts of researchers in the swine genomics community. Progress on expanding the linkage map has slowed down, but the efforts have created a higher-resolution physical map integrating the clone map and BAC end sequence. The number of QTL mapped is still growing and most of the updated QTL mapping results are available through PigQTLdb. Additionally, expression studies using high-throughput microarrays and other gene expression techniques have made significant advancements. The number of identified non-coding RNAs is rapidly increasing and their exact regulatory functions are being explored. A publishable draft (build 10) of the swine genome sequence was available for the pig genomics community by the end of December 2010. Build 9 of the porcine genome is currently available with Ensembl annotation; manual annotation is ongoing. These drafts provide useful tools for such endeavors as comparative genomics and SNP scans for fine QTL mapping. A recent community-wide effort to create a 60K porcine SNP chip has greatly facilitated whole-genome association analyses, haplotype block construction and linkage disequilibrium mapping, which can contribute to whole-genome selection. The future 'systems biology' that integrates and optimizes the information from all research levels can enhance the pig community's understanding of the full complexity of the porcine genome. These recent technological advances and where they may lead are reviewed.     

Nuclear microenvironments and cancer

Nucleic acids and regulatory proteins are architecturally organized in nuclear microenvironments. The compartmentalization of regulatory machinery for gene expression, replication and repair, is obligatory for fidelity of biological control. Perturbations in the organization, assembly and integration of regulatory machinery have been functionally linked to the onset and progression of tumorigenesis. The combined application of cellular, molecular, biochemical and in vivo genetic approaches, together with structural biology, genomics, proteomics and bioinformatics, will likely lead to new approaches in cancer diagnostics and therapy.     

Computational Biology Methods and Their Application to the Comparative Genomics of Endocellular Symbiotic Bacteria of Insects

Comparative genomics has become a real tantalizing challenge in the postgenomic era. This fact has been mostly magnified by the plethora of new genomes becoming available in a daily bases. The overwhelming list of new genomes to compare has pushed the field of bioinformatics and computational biology forward toward the design and development of methods capable of identifying patterns in a sea of swamping data noise. Despite many advances made in such endeavor, the ever-lasting annoying exceptions to the general patterns remain to pose difficulties in generalizing methods for comparative genomics. In this review, we discuss the different tools devised to undertake the challenge of comparative genomics and some of the exceptions that compromise the generality of such methods. We focus on endosymbiotic bacteria of insects because of their genomic dynamics peculiarities when compared to free-living organisms.     

Quality estimation of multiple sequence alignments by Bayesian hypothesis testing

In this work we present a web-based tool for estimating multiple alignment quality using Bayesian hypothesis testing. The proposed method is very simple, easily implemented and not time consuming with a linear complexity. We evaluated method against a series of different alignments (a set of random and biologically derived alignments) and compared the results with tools based on classical statistical methods (such as sFFT and csFFT). Taking correlation coefficient as an objective criterion of the true quality, we found that Bayesian hypothesis testing performed better on average than the classical methods we tested. This approach may be used independently or as a component of any tool in computational biology which is based on the statistical estimation of alignment quality. AVAILABILITY: http://www.fmi.ch/groups/functional.genomics/tool.htm. SUPPLEMENTARY INFORMATION: Supplementary data are available from http://www.fmi.ch/groups/functional.genomics/tool-Supp.htm.     

An enzyme mechanism language for the mathematical modeling of metabolic pathways

MOTIVATION: As a first step toward the elucidation of the systems biology of complex biological systems, it was our goal to mathematically model common enzyme catalytic and regulatory mechanisms that repeatedly appear in biological processes such as signal transduction and metabolic pathways. RESULTS: We describe kMech, a Cellerator language extension that describes a suite of enzyme mechanisms. Each enzyme mechanism is parsed by kMech into a set of fundamental association-dissociation reactions that are translated by Cellerator into ordinary differential equations that are numerically solved by Mathematica. In addition, we present methods that use commonly available kinetic measurements to estimate rate constants required to solve these differential equations.     

Culture and manipulation of insect facultative symbionts

Insects from many different taxonomic groups harbor maternally transmitted bacterial symbionts. Some of these associations are ancient in origin and obligate in nature whereas others originated more recently and are facultative. Previous research focused on the biology of ancient obligate symbionts with essential nutritional roles in their insect hosts. However, recent important advances in understanding the biology of facultative associations have been driven by the development of techniques for the culture, genetic modification and manipulation of facultative symbionts. In this review, we examine these available experimental techniques and illustrate how they have provided fascinating new insight into the nature of associations involving facultative symbionts. We also propose a rationale for future research based on the integration of genomics and experimentation.