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Concept: Functional genomics

175

As the volume, complexity and diversity of the information that scientists work with on a daily basis continues to rise, so too does the requirement for new analytic software. The analytic software must solve the dichotomy that exists between the need to allow for a high level of scientific reasoning, and the requirement to have an intuitive and easy to use tool which does not require specialist, and often arduous, training to use. Information visualization provides a solution to this problem, as it allows for direct manipulation and interaction with diverse and complex data. The challenge addressing bioinformatics researches is how to apply this knowledge to data sets that are continually growing in a field that is rapidly changing.

Concepts: Scientific method, Psychology, Bioinformatics, Genomics, Emergence, Logic, Problem solving, Functional genomics

171

Next-Generation Sequencing (NGS) technologies and Genome-Wide Association Studies (GWAS) generate millions of reads and hundreds of datasets, and there is an urgent need for a better way to accurately interpret and distill such large amounts of data. Extensive pathway and network analysis allow for the discovery of highly significant pathways from a set of disease vs. healthy samples in the NGS and GWAS. Knowledge of activation of these processes will lead to elucidation of the complex biological pathways affected by drug treatment, to patient stratification studies of new and existing drug treatments, and to understanding the underlying anti-cancer drug effects. There are approximately 141 biological human pathway resources as of Jan 2012 according to the Pathguide database. However, most currently available resources do not contain disease, drug or organ specificity information such as disease-pathway, drug-pathway, and organ-pathway associations. Systematically integrating pathway, disease, drug and organ specificity together becomes increasingly crucial for understanding the interrelationships between signaling, metabolic and regulatory pathway, drug action, disease susceptibility, and organ specificity from high-throughput omics data (genomics, transcriptomics, proteomics and metabolomics).

Concepts: Genetics, Biology, Genomics, Chemotherapy, Genome-wide association study, Proteomics, Knowledge, Functional genomics

168

ABSTRACT Microorganisms grow under a remarkable range of extreme conditions. Environmental transcriptomic and proteomic studies have highlighted metabolic pathways active in extremophilic communities. However, metabolites directly linked to their physiology are less well defined because metabolomics methods lag behind other omics technologies due to a wide range of experimental complexities often associated with the environmental matrix. We identified key metabolites associated with acidophilic and metal-tolerant microorganisms using stable isotope labeling coupled with untargeted, high-resolution mass spectrometry. We observed >3,500 metabolic features in biofilms growing in pH ~0.9 acid mine drainage solutions containing millimolar concentrations of iron, sulfate, zinc, copper, and arsenic. Stable isotope labeling improved chemical formula prediction by >50% for larger metabolites (>250 atomic mass units), many of which were unrepresented in metabolic databases and may represent novel compounds. Taurine and hydroxyectoine were identified and likely provide protection from osmotic stress in the biofilms. Community genomic, transcriptomic, and proteomic data implicate fungi in taurine metabolism. Leptospirillum group II bacteria decrease production of ectoine and hydroxyectoine as biofilms mature, suggesting that biofilm structure provides some resistance to high metal and proton concentrations. The combination of taurine, ectoine, and hydroxyectoine may also constitute a sulfur, nitrogen, and carbon currency in the communities. IMPORTANCE Microbial communities are central to many critical global processes and yet remain enigmatic largely due to their complex and distributed metabolic interactions. Metabolomics has the possibility of providing mechanistic insights into the function and ecology of microbial communities. However, our limited knowledge of microbial metabolites, the difficulty of identifying metabolites from complex samples, and the inability to link metabolites directly to community members have proven to be major limitations in developing advances in systems interactions. Here, we show that combining stable-isotope-enabled metabolomics with genomics, transcriptomics, and proteomics can illuminate the ecology of microorganisms at the community scale.

Concepts: Archaea, Bacteria, Metabolism, Mass spectrometry, Genomics, Proteomics, Metabolomics, Functional genomics

167

A sharp decline in the availability of arable land and sufficient supply of irrigation water along with a continuous steep increase in food demands have exerted a pressure on farmers to produce more with fewer resources. A viable solution to release this pressure is to speed up the plant breeding process by employing biotechnology in breeding programs. The majority of biotechnological applications rely on information generated from various -omic technologies. The latest outstanding improvements in proteomic platforms and many other but related advances in plant biotechnology techniques offer various new ways to encourage the usage of these technologies by plant scientists for crop improvement programs. A combinatorial approach of accelerated gene discovery through genomics, proteomics, and other associated -omic branches of biotechnology, as an applied approach, is proving to be an effective way to speed up the crop improvement programs worldwide. In the near future, swift improvements in -omic databases are becoming critical and demand immediate attention for the effective utilization of these techniques to produce next-generation crops for the progressive farmers. Here, we have reviewed the recent advances in proteomics, as tools of biotechnology, which are offering great promise and leading the path toward crop improvement for sustainable agriculture.

Concepts: Agriculture, Genomics, Fungus, Biotechnology, Irrigation, Functional genomics, Breeding, Agronomy

167

BACKGROUND: MultiAlign is a free software tool that aligns multiple liquid chromatography-mass spectrometry datasets to one another by clustering mass and chromatographic elution features across datasets. Applicable to both label-free proteomics and metabolomics comparative analyses, the software can be operated in several modes. For example, clustered features can be matched to a reference database to identify analytes, used to generate abundance profiles, linked to tandem mass spectra based on parent precursor masses, and culled for targeted liquid chromatography-tandem mass spectrometric analysis. MultiAlign is also capable of tandem mass spectral clustering to describe proteome structure and find similarity in subsequent sample runs. RESULTS: MultiAlign was applied to two large proteomics datasets obtained from liquid chromatography-mass spectrometry analyses of environmental samples. Peptides in the datasets for a microbial community that had a known metagenome were identified by matching mass and elution time features to those in an established reference peptide database. Results compared favorably with those obtained using existing tools such as VIPER, but with the added benefit of being able to trace clusters of peptides across conditions to existing tandem mass spectra. MultiAlign was further applied to detect clusters across experimental samples derived from a reactor biomass community for which no metagenome was available. Several clusters were culled for further analysis to explore changes in the community structure. Lastly, MultiAlign was applied to liquid chromatography-mass spectrometry-based datasets obtained from a previously published study of wild type and mitochondrial fatty acid oxidation enzyme knockdown mutants of human hepatocarcinoma to demonstrate its utility for analyzing metabolomics datasets. CONCLUSION: MultiAlign is an efficient software package for finding similar analytes across multiple liquid chromatography-mass spectrometry feature maps, as demonstrated here for both proteomics and metabolomics experiments. The software is particularly useful for proteomic studies where little or no genomic context is known, such as with environmental proteomics.

Concepts: Protein, Mass spectrometry, Genomics, Fatty acid metabolism, Chromatography, Analytical chemistry, Proteomics, Functional genomics

150

It is envisioned that a more precise study of the association between the traits and biomarkers will dramatically decrease the time and costs required to bring new improved disease resistance lines to market. The field of omics has an enormous potential to assess diseases more precise, including the identification and understanding of pathogenic mechanisms in legume crops, and have been exemplified by a relatively large number of studies. Recently, molecular genetic studies have accumulated a huge amount of genotypic data, through a more affordable next generation sequencing (NGS) technology, causing the omics approaches to fall behind. In this paper I provide an overview of genomics and proteomics and their use in legume crops, including the use of comparative genomics to identify homologous markers within legume crops.

Concepts: DNA, Gene, Genetics, Bioinformatics, Evolution, Genomics, Cultural studies, Functional genomics

150

Understanding plant’s defense mechanisms and their response to biotic stresses is of fundamental meaning for the development of resistant crop varieties and more productive agriculture. The Brassica genus involves a large variety of economically important species and cultivars used as vegetable source, oilseeds, forage and ornamental. Damage caused by pathogens attack affects negatively various aspects of plant growth, development, and crop productivity. Over the last few decades, advances in plant physiology, genetics, and molecular biology have greatly improved our understanding of plant responses to biotic stress conditions. In this regard, various ‘omics’ technologies enable qualitative and quantitative monitoring of the abundance of various biological molecules in a high-throughput manner, and thus allow determination of their variation between different biological states on a genomic scale. In this review, we have described advances in ‘omic’ tools (genomics, transcriptomics, proteomics and metabolomics) in the view of conventional and modern approaches being used to elucidate the molecular mechanisms that underlie Brassica disease resistance.

Concepts: DNA, Gene, Genetics, Biology, Genomics, Species, Qualitative research, Functional genomics

47

Personalized medicine is expected to benefit from combining genomic information with regular monitoring of physiological states by multiple high-throughput methods. Here, we present an integrative personal omics profile (iPOP), an analysis that combines genomic, transcriptomic, proteomic, metabolomic, and autoantibody profiles from a single individual over a 14 month period. Our iPOP analysis revealed various medical risks, including type 2 diabetes. It also uncovered extensive, dynamic changes in diverse molecular components and biological pathways across healthy and diseased conditions. Extremely high-coverage genomic and transcriptomic data, which provide the basis of our iPOP, revealed extensive heteroallelic changes during healthy and diseased states and an unexpected RNA editing mechanism. This study demonstrates that longitudinal iPOP can be used to interpret healthy and diseased states by connecting genomic information with additional dynamic omics activity.

Concepts: Medicine, Gene, Genetics, Epidemiology, Biology, Genomics, Proteomics, Functional genomics

28

The ethical landscape in the field of genomics is rapidly shifting. Plummeting sequencing costs, along with ongoing advances in bioinformatics, now make it possible to generate an enormous volume of genomic data about vast numbers of people. The informational richness, complexity, and frequently uncertain meaning of these data, coupled with evolving norms surrounding the sharing of data and samples and persistent privacy concerns, have generated a range of approaches to the ethical management of genomic information. As calls increase for the expanded use of broad or even open consent, and as controversy grows about how best to handle incidental genomic findings, these approaches, informed by normative analysis and empirical data, will continue to evolve alongside the science.

Concepts: Scientific method, Genetics, Bioinformatics, Genomics, Science, Empirical, Computational genomics, Functional genomics

28

Inflammatory lung diseases are highly complex in respect of pathogenesis and relationships between inflammation, clinical disease and response to treatment. Sophisticated large-scale analytical methods to quantify gene expression (transcriptomics), proteins (proteomics), lipids (lipidomics) and metabolites (metabolomics) in the lungs, blood and urine are now available to identify biomarkers that define disease in terms of combined clinical, physiological and patho-biological abnormalities. The aspiration is that these approaches will improve diagnosis, i.e., define pathological phenotypes, and facilitate the monitoring of disease and therapy and, also, unravel underlying molecular pathways. Biomarker studies can either select pre-defined biomarker(s) measured by specific methods or apply an “unbiased” approach involving detection platforms that are indiscriminate in focus. This article reviews the technologies presently available to study biomarkers of lung disease within the ‘omics field. The contributions of the individual 'omics analytical platforms to the field of respiratory diseases are summarised, with the goal of providing background on their respective abilities to contribute to systems medicine-based studies of lung disease.

Concepts: Gene, Cancer, Diseases and disorders, Respiratory disease, Pulmonology, Proteomics, Functional genomics, Systems biology