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Integrative analysis of large-scale biological data sets
Get PDFWe present two novel web-applications for microarray and gene/protein set analysis, ArrayMining.net and TopoGSA. These bioinformatics tools use integrative analysis methods, including ensemble and consensus machine learning techniques, as well as modular combinations of different analysis types, to extract new biological insights from experimental transcriptomics and proteomics data. They enable researchers to combine related algorithms and datasets to increase the robustness and accuracy of statistical analyses and exploit synergies of different computational methods, ranging from statistical learning to optimization and topological network analysis
Different Approaches For Protein Engineering In Industrial Biotechnology
Get PDFProtein engineering is the novel field which has wide applications from pharmaceutics, industry, commercial, laundry and research. It may apply rational design or non rational design or both. Site directed mutagenesis is a classical approach involving the protein folding principles and as such different techniques involving multidisciplinary research and broad knowledge is required involving biocomputing of complex data obtained from various sequencing projects and prediction of the future protein structure either chemically or genetically modified. Non rational mutagenesis or directed evolution involves random mutations in the gene encoding protein or shuffling the genes encoding different domains producing a random set of numerous large libraries of mutant proteins, using advanced technology the desired protein can be selected but the exact structure or changes may remain unnoticed
Three mutations in SASH1 cause the pathogenesis of dyschromatosis universalis hereditaria (DUH)
Get PDFDyschromatosis universalis hereditaria (DUH) is a rare genodermatosis characterized by hyper- and hypopigmented macules which form a reticulate or mottled pattern. The causal gene and the precise pathogenesis of DUH have been unclear since the disease was initially reported in 1933. However, we found three heterozygous mutations encoding amino acid substitutions in SASH1 in each of three nonconsanguineous DUH families. Immunohistochemistry and melanin staining showed distribution heterogenicity of melanocytes, predominantly melanized melanocytes in the epidermal tissues of a DUH patient. Specifically, we identified that mutations of SASH1 can up-regulate resident melanogenic proteins, transport proteins of melanosome, and induce increased mobility of melanocytes in vitro and in vivo. Furthermore, SASH1 was shown to interact with several proteins associated with melanogenesis in the MAPK signaling pathway and the endothelin signaling pathway, indicating an additional melanogenesis signaling pathway in the regulation of melanin biosynthesis. Collectively, these observations suggest that DUH is a heterogeneous disorder of increased production and transport of melanosomes caused by SASH1 mutation together with melanocyte maldistribution
Large sets of edit-metric sequence identification tags to facilitate large-scale multiplexing of reads from massively parallel sequencing
No full text*Background*
Massively parallel DNA sequencing technologies provide exponential increases in the amount of data returned from the sequencing process, relative to traditional (Sanger-based) techniques. Use of unique, synthetic oligonucleotides (identifying sequence tags) on each sample enables the deconvolution of samples pooled prior to massively parallel sequencing. To counteract oligonucleotide synthesis and sequencing errors, sequence tags should be drawn from combinations with sufficient differences and with an appropriate error-correcting code over the alphabet [A,C,G,T]. This method ensures that errors within the tags do not cause sequences to be assigned to the wrong sample while also enabling correction and recovery of incorrectly-sequenced or incorrectly-synthesized tags. The set of available tags should be large, allowing sample multiplexing to scale with rapid changes in sequencing platform output. The set of tags should also account for errors possible during both the oligonucleotide synthesis and sequencing processes. Most tags in current use have been designed to maintain a particular Hamming distance: a scheme that ensures the distance between tag sequences is maintained in the presence of substitutions. However, sequence identification tags conforming to the edit-metric are more appropriate: edit-metric sequence tags are robust to insertions, deletions, and substitution errors. 

*Results*
We present edittag, a python package containing several tools to facilitate the design of edit-metric-based sequence identification tags, check existing sets of sequence identification tags for conformance to the edit-metric, and apply sequence identification tags to primers and/or adapters. We use edittag to design several large sets of edit-metric sequence tags ranging from four to 10 nucleotides in length and edit distance three to nine. Finally, we test a set of fusion primers designed with the software developed here, demonstrating high levels of successful amplification. 

*Conclusions*
Researchers using sequence identification tags should consider using edit-metric-based sequence tags in place of the more common, Hamming-distance-based alternatives. Edit-metric sequence tags are robust to insertion, deletion, and substitution errors, thus more robust to all forms of error present during the DNA sequencing process. Edittag facilitates the generation and application of these robust sequence tags.

Kinetic model based on molecular mechanism for action potential
Get PDFThe Hodgkin-Huxley model for action potentials has been widely used but was not built on a microscopic description of the neuronal membrane. Through molecular dynamics simulations, the molecular mechanism of the channel currents is becoming clear. However, the quantitative link between molecular mechanism and action potential remains to be elucidated. Here, a kinetic model for action potential based on the molecular mechanism of the channel currents is proposed. Using it, the experimental observations about action potential are reproduced quantitatively and explained based on molecular mechanism. We find that the accumulation of Na+ ions near exit of the electivity filter is the dominant event to cause the refractory period of the Na+ channel and the types of the channel currents depend on its rate constants. The channel inductance represents the inertia of the channel to retain a certain ion binding state, the channel resistances include ones against state transition and charge transfer
Getting The Most Out of Your Research
Get PDFResearch is the cornerstone of invention, facilitator of innovation, and mother of discovery. Even though many students are competent in advancing through the class room and getting good grades, excellent research requires a different set of attitudinal and academic skills. This workshop, "Get the most out of your research" is an outstanding program developed from extensive time spent with brilliant scientists and a wide variety of mentored students. Familiarize yourself with the fine points of this workshop and arm yourself for a successful research career
Nationwide Study of Breast Cancer Risk Factors in Latinas
Get PDFBreast cancer is the most common cancer among American women. Any woman can be affected by breast cancer, with risk for the disease increasing with age. Risk for breast cancer is also exacerbated in women who have certain genetic alterations. Mutations in the BRCA1 and BRCA2 genes predispose women to breast and ovarian cancer, and are increasingly recognized in prostate and pancreatic cancers (1-3). In Caucasian and Asian ethnicities BRCA mutations are associated with basal-type/triple-negative disease. However this association between BRCA gene mutations and basal/triple-negative disease has been understudied in other ethnicities (4-6). The incidence and mortality of breast cancer of Hispanics and Native Americans are lower than other ethnicities; however they are underrepresented in epidemiological and clinical studies. Further, it is known that common recurrent mutations in BRCA1 and BRCA2 genes exist in Hispanic/Latino communities which account for 35-45% of mutation carriers (7, 8). The objective of our study is thus to investigate triple-negative disease and BRCA gene mutations in Hispanic women
SNPxGE2: a database for human 3-way SNP-expression associations
Get PDFRecently, gene co-expression relationships have been found to be often conditional and dynamic. Besides, many studies have suggested that single nucleotide polymorphisms (SNPs) have impacts on gene expression variations in human populations. The SNPxGE2 database contains the computationally predicted human 3-way SNP-expression associations, that is, the differential co-expression between 2 genes is associated with a genotype/SNP. This data was generated from a large scale association study that was based on the HapMap data, which covered 269 individuals from 4 human populations, 701,202 SNPs and 15,000 gene expression profiles. Two models of 3-way SNP-expression associations were considered: gap/substitution and on/off. The implementation was carried out using 64 Linux cluster nodes in ~30 days and assessed SNP-expression combinations. The results, including 4,713 on/off associations and 36,170 gap/substitution associations at a p-value cutoff of 0.001, can be queried in the SNPxGE2 database via either gene name or reference SNP ID. For each reported association, a detailed information page is provided. The SNPxGE2 database can be freely accessed at http://tunisia.ads.uga.edu/SNPxGE2/index.php
Isolation of new racemic sugar (D/L galacturonic acid) from leaves of Paederia foetida Linn.
Get PDFNew racemic sugars (D/L galacturonic acid) were isolate from the leaves of Paederia foetida Linn by the column chromatography. Identification of these isolated compound achieved by TLC, 1H-NMR, 13C-NMR, FTIR and Mass spectral data
Sensory adaptation in the light of information and energy
No full textSignal processing in neurons is constrained by internal noise and energy consumption. Neural systems often invest energy in amplifying signals to protect them against internal noise. There is no general expression for the trade-off between energy and information, because it is strongly dependent on the properties of signal, noise and underlying mechanism. We present the first analysis of this energy-information trade-off in a specific system, the R1-6 photoreceptors of the blowfly, Calliphora vicina. These photoreceptors adapt to light level by adjusting their transduction gain (number of light-gated channels opened per photon) and potassium conductance. By combining experimental measures of photoreceptor impedances, transfer functions and signal quality in a basic membrane model we discovered that photoreceptors do not adapt to maximise their sensitivity. Instead, they use a lower sensitivity at which they capture 99% of the information from naturalistic stimuli. This strategy is efficient because it avoids the wasteful amplification of noisy inputs and reduces energy consumption