Systematic control of protein interactions for systems biology

Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 12/2011; 108(51):20279-80. DOI: 10.1073/pnas.1118084109
Source: PubMed
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    ABSTRACT: Chromatin immunoprecipitation followed by sequencing (ChIP-seq) is a technique for genome-wide profiling of DNA-binding proteins, histone modifications or nucleosomes. Owing to the tremendous progress in next-generation sequencing technology, ChIP-seq offers higher resolution, less noise and greater coverage than its array-based predecessor ChIP-chip. With the decreasing cost of sequencing, ChIP-seq has become an indispensable tool for studying gene regulation and epigenetic mechanisms. In this Review, I describe the benefits and challenges in harnessing this technique with an emphasis on issues related to experimental design and data analysis. ChIP-seq experiments generate large quantities of data, and effective computational analysis will be crucial for uncovering biological mechanisms.
    Nature Reviews Genetics 10/2009; 10(10):669-80. DOI:10.1038/nrg2641 · 39.79 Impact Factor
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    ABSTRACT: A cell's behavior is a consequence of the complex interactions between its numerous constituents, such as DNA, RNA, proteins and small molecules. Cells use signaling pathways and regulatory mechanisms to coordinate multiple processes, allowing them to respond to and adapt to an ever-changing environment. The large number of components, the degree of interconnectivity and the complex control of cellular networks are becoming evident in the integrated genomic and proteomic analyses that are emerging. It is increasingly recognized that the understanding of properties that arise from whole-cell function require integrated, theoretical descriptions of the relationships between different cellular components. Recent theoretical advances allow us to describe cellular network structure with graph concepts and have revealed organizational features shared with numerous non-biological networks. We now have the opportunity to describe quantitatively a network of hundreds or thousands of interacting components. Moreover, the observed topologies of cellular networks give us clues about their evolution and how their organization influences their function and dynamic responses.
    Journal of Cell Science 12/2005; 118(Pt 21):4947-57. DOI:10.1242/jcs.02714 · 5.33 Impact Factor
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    ABSTRACT: Fluorescence probes based on the principle of Förster resonance energy transfer (FRET) have shed new light on our understanding of signal transduction cascades. Among them, unimolecular FRET probes containing fluorescence proteins are rapidly increasing in number because these genetically encoded probes can be easily loaded into living cells and allow simple acquisition of FRET images. We have developed probes for small GTPases, tyrosine kinases, serine-threonine kinases and phosphoinositides. Images obtained with these probes have revealed that membrane protrusions such as nascent lamellipodia or neurites provide an active signalling platform in the growth factor-stimulated cells.
    Philosophical Transactions of The Royal Society B Biological Sciences 07/2008; 363(1500):2143-51. DOI:10.1098/rstb.2008.2267 · 6.31 Impact Factor


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