Identifying subcellular localizations of mammalian protein complexes based on graph theory with a random forest algorithm
Zhan-Chao Li, Yan-Hua Lai, Li-Li Chen, Chao Chen, Yun Xie, Zong Dai and Xiao-Yong Zou 
DOI: 10.1039/C3MB25451H

A study of Caenorhabditis elegans DAF-2 mutants by metabolomics and differential correlation networks
Cecilia Castro, Jan Krumsiek, Nicolas J. Lehrbach, Steven A. Murfitt, Eric A. Miska and Julian L. Griffin
DOI: 10.1039/C3MB25539E

DNA thermodynamic stability and supercoil dynamics determine the gene expression program during the bacterial growth cycle
Patrick Sobetzko, Monika Glinkowska, Andrew Travers and Georgi Muskhelishvili 
DOI: 10.1039/C3MB25515H

Proteomic and ionomic profiling reveals significant alterations of protein expression and calcium homeostasis in cystic fibrosis cells
Domenico Ciavardelli, Melania D’Orazio, Luisa Pieroni, Ada Consalvo, Claudia Rossi, Paolo Sacchetta, Carmine Di Ilio, Andrea Battistoni and Andrea Urbani 
DOI: 10.1039/C3MB25594H

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PCR is normally needed to amplify the quantity of natural DNA samples for visual detection before they can be detected. For point-of-care applications in particular, the need for a PCR machine is cumbersome. In this communication, the researchers demonstrate a method for specific visual detection of a DNA sample without the need for PCR.

Gold nanoparticles are often coated with ligands for target specific detection. The different inter-particle distances provide a visual output when the target is added. Well-dispersed gold nanoparticles appear read and as the distance decreases this colour changes down the spectrum to purple and then to blue. Aggregation of the nanoparticles causes them to precipitate as black or grey sediments. It has been shown before that synthetic DNA sequences can be detected in this way using thiolated ligands. This study uses double stranded DNA samples at room temperature – surprising as single stranded DNA is optimal for adsorbing to the gold nanoparticle surface.

The researchers test their simple assay on genomic DNA extracts from Salmonella enterica. The sensitivity of the system leaves much to be desired compared to when PCR is used, however this easy protocol at room temperature with readily available agents and no need for electricity has some great advantages. The lack of PCR in detection of genomic DNA is a positive step forward for point-of-care diagnostics.

This short and urgent Communication is now free to access for the next four weeks*:

Direct visual detection of Salmonella genomic DNA using gold nanoparticles
Kamaladasan Kalidasan, Jia Ling Neo and Mahesh Uttamchandani
DOI: 10.1039/C3MB25527A

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This fascinating HOT review from Beena Kadakkuzha and Sathyanarayanan Puthanveettil at The Scripps Research Institute, USA, delves into the tools we can use to understand neural proteomics and genomics, why this is useful and how we can pull the information together to explain observations of higher brain function. They include: 

1. Relationship between gene expression and brain function
2. The need for functional genomics and proteomics
3. Sequencing, microarrays and next generation sequencing
4. Genomic databases
5. Single cell analysis
6. High-throughput challenges

This truly interesting review is now free to access for four weeks*, so you can read it now:

Genomics and proteomics in solving brain complexity
Beena M. Kadakkuzha and Sathyanarayanan V. Puthanveettil
DOI: 10.1039/C3MB25391K

                  

This is followed by an Opinion piece from Matthias Gstaiger and Ruedi Aebersold at ETH Zurich, Switzerland, on the increasing understanding of genotype-phenotype relationships due to deciphering proteome organisation.

Digital and analogical reality in proteomics investigation
Andrea Urbani, Massimo Castagnola, Mauro Fasano, Luca Bini, Alessandra Modesti, Anna Maria Timperio and Paola Roncada 
DOI: 10.1039/C3MB90013D

Genotype–phenotype relationships in light of a modular protein interaction landscape
Matthias Gstaiger and Ruedi Aebersold 
DOI: 10.1039/C3MB25583B

Amongst the three review articles in this Proteomics themed issue, a HOT review article by Jorg Stulke et al. at Georg-August-Universitat Gottingen, Germany, is featured on the front cover. This review taking a fresh look at the genes and proteins of Bacillus subtilis was featured on the blog recently. It highlights the difficulties with defining the essential genes of a particular organism.

Essential genes in Bacillus subtilis: a re-evaluation after ten years
Fabian M. Commichau, Nico Pietack and Jörg Stülke 
DOI: 10.1039/C3MB25595F

The inside front cover features work from Damiana Pieragostino et al. in Italy in which shotgun proteomics is used to provide a profile of the proteins in the tears of patients with primary open angle glaucoma. They find a mix of inflammatory proteins as possible biomarkers for early diagnosis of the disease, which is a major global cause of blindness.

Shotgun proteomics reveals specific modulated protein patterns in tears of patients with primary open angle glaucoma naïve to therapy
Damiana Pieragostino, Luca Agnifili, Vincenzo Fasanella, Simona D’Aguanno, Rodolfo Mastropasqua, Carmine Di Ilio, Paolo Sacchetta, Andrea Urbani and Piero Del Boccio
DOI: 10.1039/C3MB25463A

The Proteomics issue is packed with more reviews, communications, a Method article and several HOT articles, see the full contents list here.

                  

Acetylation of proteins happens after they have been synthesised by translation and can change a protein’s properties markedly. It is thought to occur in disordered regions of proteins. The level of acetylation can be studied over the whole proteome and this is termed the acetylome. This study describes a comprehensive bioinformatics analysis of the acetylome of Toxoplasma at a particular stage of the life cycle. They look specifically at the disorder status of acetylated versus non-acetylated lysines. They conclude that dramatic change takes place when the parasite transitions during its life cycle from an intracellular to extracellular environment.

Free to access for the next 4 weeks*, you can read the discussion of their results now:

Protein intrinsic disorder in the acetylome of intracellular and extracellular Toxoplasma gondii
Bin Xue, Victoria Jeffers, William J. Sullivan and Vladimir N. Uversky
DOI: 10.1039/C3MB25517D

                  

In this HOT article, using a divergent synthetic approach Fukase et al. synthesize the lipophilic terminals, known as lipid As, of lipopolysaccharides from Gram-negative bacteria H. pylori and P. gingivalis. They study the structures’ cytokine induction activities, which are indicative of their immune function.

From this synthetic study, they explain the link between P. gingivalis infection and atherosclerosis. Lipid A 1 and 2 selectively induce IL-18 and inhibit IL-6 and IL-8, and a link between IL-18 and atherosclerosis is known.

Read their interesting divergent synthesis procedure and conclusions in full, as this HOT article is free to access for the next 4 weeks*:

Dual-labeled glycoclusters: synthesis and their application in monitoring lectin-mediated endocytosis
Xizhe Tian, Kyung-Hwa Baek and Injae Shin 
DOI: 10.1039/C3MB25491G

                  

In this HOT article, researchers at Donghua University, China, and the Gordon Life Science Institute, California, USA, propose a new multi-label learning approach.  They use a new predictor specialised for predicting the subcellular locations of animal proteins with both single and multiple sites to improve upon the various shortcomings of previous methods.

They define a new statistical predictor, iLoc-Animal, using a new classification involving protein sequences and a Gene Ontology approach. Five metrics were defined to rigorously measure the prediction quality. They cross-validate the system using a benchmarked dataset of 5000 different animal proteins and 20 defined subcellular locations where these proteins locate, including the cell membrane and mitochondria. This is an incredibly complex system, making the achievement of formulating a useful high-throughput predictor tool significant.

This HOT article is now free to access for the next 4 weeks* and the authors have also make the web-server iLoc-Animal freely accessible at http://www.jci-bioinfo.cn/iLoc-Animal. 

iLoc-Animal: a multi-label learning classifier for predicting subcellular localization of animal proteins
Wei-Zhong Lin, Jian-An Fang, Xuan Xiao and Kuo-Chen Chou
DOI: 10.1039/C3MB25466F

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Michael Washburn received his B.A. in chemistry from Grinnell College (Iowa, USA).  He then started his graduate studies at Michigan State University and received a Ph.D. in 1998 under the supervision of Prof. William W. Wells.  He then conducted post-doctoral training in proteomics in the Department of Molecular Biotechnology at the University of Washington with Dr. John R. Yates, III.   In 2000, he moved to San Diego with Dr. Yates and worked at the Torrey Mesa Research Institute as a staff scientist and a senior staff scientist.  In 2003, he started his independent career as the Director of Proteomics at the Stowers Institute for Medical Research in Kansas City, MO, USA.   His research interests are in quantitative proteomics and systems biology with a particular focus on the analysis of transcriptional regulatory complexes and chromatin remodeling complexes and their protein interaction networks.  He has published more than 140 scientific papers to date.

Below, Dr. Washburn shares his view on quantitative proteomics, systems biology, and the research areas he is working in currently:

                  

Led by Anna Panchenko, their focus is on protein binding in relation to intrinsically disordered human protein complexes i.e. proteins with no single defined structure.  Some disordered proteins are thought to undergo folding when binding to another protein interface, causing a change from disorder to order.  

In this work, the team find that phosphorylation, binding and disorder–order transitions are all related processes. Disorder and binding states affect phosphorylation of serine more than threonine.  Tyrosine is more often in ordered protein interfaces, explaining why tyrosine phosphorylation is often associated with structured domains. On the other hand, serine is usually found in disordered regions especially in protein–protein interaction networks and the researchers conclude that this is due to the vital role of serine in disorder–order transitions.

The work also goes into mechanisms of how intrinsic disorder is involved in the way phosphorylation affects binding. The team ask how phosphorylation might prevent disorder–order transitions occurring during a binding event. Phosphorylation sites have a direct role in binding and binding regulated by disorder is known to have a number of advantages. The association of these influences is the logical conclusion of this work, now free to access for 4 weeks*:

Regulation of protein–protein binding by coupling between phosphorylation and intrinsic disorder: analysis of human protein complexes
Hafumi Nishi, Jessica H. Fong, Christiana Chang, Sarah A. Teichmann and Anna R. Panchenko
DOI: 10.1039/C3MB25514J

                  

17- 21 June 2013, Loughborough University, UK

Don’t miss your chance to be part of the RSC Medicinal Chemistry Residential School, an intensive course which has trained some of the world’s leading medicinal chemists working in the pharmaceutical industry.

The early bird registration deadline of Monday 22 April 2013 is almost upon us. If you are a graduate or post-doctoral chemist with 1-5 years’ experience in the field of drug research or a final year PhD student in pharmacy and organic chemistry contemplating a career in medicinal chemistry, be sure to secure your space before this date to benefit from a great saving on the standard fee.

Please visit the dedicated webpage for full details about the RSC Medicinal Chemistry Residential School including the course programme, bursary applications and poster presentation opportunities.