PubMed

Related Articles A sex-inducing pheromone triggers cell cycle arrest and mate attraction in the diatom Seminavis robusta. Sci Rep. 2016;6:19252 Authors: Moeys S, Frenkel J, Lembke C, Gillard JT, Devos V, Van den Berge K, Bouillon B, Huysman MJ, De Decker S, Scharf J, Bones A, Brembu T, Winge P, Sabbe K, Vuylsteke M, Clement L, De Veylder L, Pohnert G, Vyverman W Abstract Although sexual reproduction is believed to play a major role in the high diversification rates and species richness of diatoms, a mechanistic understanding of diatom life cycle control is virtually lacking. Diatom sexual signalling is controlled by a complex, yet largely unknown, pheromone system. Here, a sex-inducing pheromone (SIP(+)) of the benthic pennate diatom Seminavis robusta was identified by comparative metabolomics, subsequently purified, and physicochemically characterized. Transcriptome analysis revealed that SIP(+) triggers the switch from mitosis-to-meiosis in the opposing mating type, coupled with the transcriptional induction of proline biosynthesis genes, and the release of the proline-derived attraction pheromone. The induction of cell cycle arrest by a pheromone, chemically distinct from the one used to attract the opposite mating type, highlights the existence of a sophisticated mechanism to increase chances of mate finding, while keeping the metabolic losses associated with the release of an attraction pheromone to a minimum. PMID: 26786712 [PubMed - in process]

Related Articles NMR- and LC-MS/MS-based urine metabolomic investigation of the subacute effects of hexabromocyclododecane in mice. Environ Sci Pollut Res Int. 2016 Jan 20; Authors: Wang D, Zhang P, Wang X, Wang Y, Zhou Z, Zhu W Abstract In the present study, both untargeted and targeted metabolomics approaches were used to evaluate the subacute effects of hexabromocyclododecane (HBCD) on mice urine metabolome. Untargeted metabolomics based on (1)H NMR showed that HBCD exposure disturbed mice metabolism in both dosed groups, especially in high dosed group. The low-dose HBCD led to a decrease in alanine, malonic acid, and trimethylamine (TMA). High-dose HBCD-treated mice developed high levels of citric acid and 2-ketoglutarate, together with decreased alanine, acetate, formate, TMA, 3-hydroxybutyrate, and malonic acid. Targeted metabolomics for metabolic profiling of 20 amino acids identified alanine, lysine, and phenylalanine as significantly disturbed metabolites. These results indicated that subchronic exposure to HBCD caused a disturbance of mice metabolism, especially in TCA cycle, lipid metabolism, gut microbial metabolism, and homeostasis of amino acids, and the application of untargeted and targeted metabolomics combined with conventional toxicology approaches to evaluate the subacute effects of pollutants will provide more comprehensive information and aid in predicting health risk of these pollutants. PMID: 26786581 [PubMed - as supplied by publisher]

Related Articles A Snapshot of the Plant Glycated Proteome: Structural, Functional and Mechanistic Aspects. J Biol Chem. 2016 Jan 19; Authors: Bilova T, Lukasheva E, Brauch D, Greifenhagen U, Paudel G, Tarakhovskaya E, Frolova N, Mittasch J, Balcke GU, Tissier A, Osmolovskaya N, Vogt T, Wessjohann LA, Birkemeyer C, Milkowski C, Frolov A Abstract Glycation is the reaction of carbonyl compounds (reducing sugars and α-dicarbonyls) with amino acids, lipids, and proteins, yielding early and advanced glycation end-products (AGEs). The AGEs can be formed via degradation of early glycation intermediates (glycoxidation) and by interaction with the products of monosaccharide autoxidation (autoxidative glycosylation). Though formation of these potentially deleterious compounds is well-characterized in animal systems and thermally treated foods, only little information about advanced glycation in plants is available. Thus, the knowledge of the plant AGE patterns and the underlying pathways of their formation are completely missing. To fill this gap, we describe the AGE-modified proteome of Brassica napus and characterize individual sites of advanced glycation by the methods of liquid chromatography-based bottom-up proteomics. The modification patterns were complex, but reproducible: 789 AGE-modified peptides in 772 proteins were detected in two independent experiments. In contrast, only 168 polypeptides contained early glycated lysines, not resembling, however, the sites of advanced glycation. Similar observations were done with Arabidopsis thaliana. The absence of the early glycated precursors of the AGE-modified protein residues indicated autoxidative glycosylation, but not glycoxidation, as the major pathway of AGE formation. To prove this assumption and to identify the potential modifying agents, we estimated the reactivity and glycative potential of plant-derived sugars using model peptide approach and liquid chromatography-mass spectrometry-based techniques. Evaluation of these datasets together with the assessed tissue carbohydrate contents revealed dihydroxyacetone phosphate, glyceraldehyde-3-phosphate, ribulose, erythrose, and sucrose as potential precursors of plant AGEs. PMID: 26786108 [PubMed - as supplied by publisher]

Related Articles Metabolomic Profiling of Mice Serum during Toxoplasmosis Progression Using Liquid Chromatography-Mass Spectrometry. Sci Rep. 2016;6:19557 Authors: Zhou CX, Zhou DH, Elsheikha HM, Zhao Y, Suo X, Zhu XQ Abstract Better understanding of the molecular changes associated with disease is essential for identifying new routes to improved therapeutics and diagnostic tests. The aim of this study was to investigate the dynamic changes in the metabolic profile of mouse sera during T. gondii infection. We carried out untargeted metabolomic analysis of sera collected from female BALB/c mice experimentally infected with the T. gondii Pru strain (Genotype II). Serum samples were collected at 7, 14 and 21 day post infection (DPI) from infected and control mice and were subjected to liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS)-based global metabolomics analysis. Multivariate statistical analysis identified 79 differentially expressed metabolites in ESI+ mode and 74 in ESI- mode in sera of T. gondii-infected mice compared to the control mice. Further principal component analysis (PCA) and partial least squares-discrimination analysis (PLS-DA) identified 19 dysregulated metabolites (5 in ESI+ mode and 14 in ESI- mode) related to the metabolism of amino acids and energy metabolism. The potential utility of these metabolites as diagnostic biomarkers was validated through receiver operating characteristic (ROC) curve analysis. These findings provide putative metabolite biomarkers for future study and allow for hypothesis generation about the pathophysiology of toxoplasmosis. PMID: 26785939 [PubMed - in process]

Related Articles Distinct mutation accumulation rates among tissues determine the variation in cancer risk. Sci Rep. 2016;6:19458 Authors: Hao D, Wang L, Di LJ Abstract Cancer is believed to be a result of accumulated mutations. However, this concept has not been fully confirmed owing to the impossibility of tracking down the ancestral somatic cell. We sought to verify the concept by exploring the correlation between cancer risk and mutation accumulation among different tissues. We hypothesized that the detected mutations through bulk tumor sequencing are commonly shared in majority, if not all, of tumor cells and are therefore largely a reflection of the mutations accumulated in the ancestral cell that gives rise to tumor. We collected a comprehensive list of mutation frequencies revealed by bulk tumor sequencing, and investigated its correlation with cancer risk to mirror the correlation between mutation accumulation and cancer risk. This revealed an approximate 1:1 relationship between mutation frequency and cancer risk in 41 different cancer types based on the sequencing data of 5,542 patients. The correlation strongly suggests that variation in cancer risk among tissues is mainly attributable to distinct mutation accumulation rates. Moreover, the correlation establishes a baseline to evaluate the effect of non-mutagenic carcinogens on cancer risk. Finally, our mathematic modeling provides a reasonable explanation to reinforce that cancer risk is predominantly determined by the first rate-limiting mutation. PMID: 26785814 [PubMed - in process]

Related Articles Phenotypic characterization of nanshi oral liquid alters metabolic signatures during disease prevention. Sci Rep. 2016;6:19333 Authors: Zhang A, Liu Q, Zhao H, Zhou X, Sun H, Nan Y, Zou S, Ma CW, Wang X Abstract This paper was designed to investigate the phenotypic characterization of Nanshi Oral Liquid (NOL) alters metabolic signatures of the 'Kidney Yang Deficiency syndrome' (KYDS). Urine metabolites were profiled by UPLC-ESI-Q-TOF-HDMS. The significantly changed metabolites such as xanthurenic acid, 4,8-dihydroxyquinoline, 3-methyldioxyindole, 4,6-dihydroxyquinoline, kynurenic acid, hippuric acid, taurine, tyramine, and 3-metanephrine, had been identified, and were related to the disturbance in tyrosine metabolism, steroid hormone biosynthesis, taurine and hypotaurine metabolism, tryptophan metabolism, phenylalanine metabolism and lysine degradation, which were helpful to further understanding the KYDS and intervention mechanism of NOL. The biochemical result showed that NOL can alleviate the kidney impairment induced by KYDS. Metabolomics results indicated the significantly changed metabolites were found to be reasonable in explaining the action mechanism of NOL. Interestingly, the effectiveness of NOL against KYDS was proved using the established metabolomics method and regulated the biomarkers as well as adjusted the metabolic disorder pathways. NOL had potentially pharmacological effect through regulating multiple perturbed pathways to normal state. This work showed that the metabolomics method was a powerful approach for studying the phenotypic characterization of disease's syndrome during disease prevention and its intervention mechanism. PMID: 26785698 [PubMed - in process]

Related Articles Behavioural and molecular endophenotypes in psychotic disorders reveal heritable abnormalities in glutamatergic neurotransmission. Transl Psychiatry. 2015;5:e540 Authors: Scoriels L, Salek RM, Goodby E, Grainger D, Dean AM, West JA, Griffin JL, Suckling J, Nathan PJ, Lennox BR, Murray GK, Bullmore ET, Jones PB Abstract Psychotic disorders such as schizophrenia are biologically complex and carry huge population morbidity due to their prevalence, persistence and associated disability. Defined by features such as delusions and hallucinations, they involve cognitive dysfunction and neurotransmitter dysregulations that appear mostly to involve the dopaminergic and glutamatergic systems. A number of genetic and environmental factors are associated with these disorders but it has been difficult to identify the biological pathways underlying the principal symptoms. The endophenotype concept of stable, heritable traits that form a mechanistic link between genes and an overt expression of the disorder has potential to reduce the complexity of psychiatric phenotypes. In this study, we used a genetically sensitive design with individuals with a first episode of psychosis, their non-affected first-degree relatives and non-related healthy controls. Metabolomic analysis was combined with neurocognitive assessment to identify multilevel endophenotypic patterns: one concerned reaction times during the performance of cognitive and emotional tests that have previously been associated with the glutamate neurotransmission system, the other involved metabolites involved directly and indirectly in the co-activation of the N-methyl-D-aspartate receptor, a major receptor of the glutamate system. These cognitive and metabolic endophenotypes may comprise a single construct, such that genetically mediated dysfunction in the glutamate system may be responsible for delays in response to cognitive and emotional functions in psychotic disorders. This focus on glutamatergic neurotransmission should guide drug discovery and experimental medicine programmes in schizophrenia and related disorders. PMID: 25826115 [PubMed - indexed for MEDLINE]

Related Articles Technical and clinical aspects of cortisol as a biochemical marker of chronic stress. BMB Rep. 2015 Apr;48(4):209-16 Authors: Lee do Y, Kim E, Choi MH Abstract Stress is now recognized as a universal premorbid factor associated with many risk factors of various chronic diseases. Acute stress may induce an individual's adaptive response to environmental demands. However, chronic, excessive stress causes cumulative negative impacts on health outcomes through "allostatic load". Thus, monitoring the quantified levels of long-term stress mediators would provide a timely opportunity for prevention or earlier intervention of stress-related chronic illnesses. Although either acute or chronic stress could be quantified through measurement of changes in physiological parameters such as heart rate, blood pressure, and levels of various metabolic hormones, it is still elusive to interpret whether the changes in circulating levels of stress mediators such as cortisol can reflect the acute, chronic, or diurnal variations. Both serum and salivary cortisol levels reveal acute changes at a single point in time, but the overall long-term systemic cortisol exposure is difficult to evaluate due to circadian variations and its protein-binding capacity. Scalp hair has a fairy predictable growth rate of approximately 1 cm/month, and the most 1 cm segment approximates the last month's cortisol production as the mean value. The analysis of cortisol in hair is a highly promising technique for the retrospective assessment of chronic stress. PMID: 25560699 [PubMed - indexed for MEDLINE]

Related Articles Acclimatisation-induced stress influenced host metabolic and gut microbial composition change. Mol Biosyst. 2015 Jan;11(1):297-306 Authors: Yap IK, Kho MT, Lim SH, Ismail NH, Yam WK, Chong CW Abstract Understanding the basal gut bacterial community structure and the host metabolic composition is pivotal for the interpretation of laboratory treatments designed to answer questions pertinent to host-microbe interactions. In this study, we report for the first time the underlying gut microbiota and systemic metabolic composition in BALB/c mice during the acclimatisation period. Our results showed that stress levels were reduced in the first three days of the study when the animals were subjected to repetitive handling daily but the stress levels were increased when handling was carried out at lower frequencies (weekly). We also observed a strong influence of stress on the host metabolism and commensal compositional variability. In addition, temporal biological compartmental variations in the responses were observed. Based on these results, we suggest that consistency in the frequency and duration of laboratory handling is crucial in murine models to minimise the impact of stress levels on the commensal and host metabolism dynamics. Furthermore, caution is advised in consideration of the temporal delay effect when integrating metagenomics and metabonomics data across different biological matrices (i.e. faeces and urine). PMID: 25382376 [PubMed - indexed for MEDLINE]

20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2016/01/20PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Metabolomic biomarkers identify differences in milk produced by Holstein cows and other minor dairy animals. J Proteomics. 2016 Jan 9; Authors: Yang Y, Zheng N, Zhao X, Zhang Y, Han R, Yang J, Zhao S, Li S, Guo T, Zang C, Wang J Abstract Several milk metabolites are associated with breeds or species of dairy animals. A better understanding of milk metabolites from different dairy animals would advance their use in evaluating milk traits and detecting milk adulteration. The objective of this study was to characterize the milk metabolite profiles of Chinese Holstein, Jersey, yak, buffalo, goat, camel, and horse and identify any differences using non-targeted metabolomic approaches. Milk samples were tested using nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-tandem mass spectrometry (LC-MS). Data were analyzed using a multivariate analysis of variance and differences in milk metabolites between Holstein and the other dairy animals were assessed using orthogonal partial least-squares discriminant analysis. Differential metabolites were identified and some metabolites, such as choline and succinic acid, were used to distinguish Holstein milk from that of the other studied animals. Metabolic pathway analysis of different metabolites revealed that glycerophospholipid metabolism as well as valine, leucine, and isoleucine biosynthesis were shared in the other ruminant animals (Jersey, buffalo, yak, and goat), and biosynthesis of unsaturated fatty acids was shared in the non-ruminant animals (camel and horse). These results can be useful for gaining a better understanding of the differences in milk synthesis between Holstein and the other dairy animals. PMID: 26779989 [PubMed - as supplied by publisher]

Microbial Small Talk: Volatiles in Fungal-Bacterial Interactions. Front Microbiol. 2015;6:1495 Authors: Schmidt R, Etalo DW, de Jager V, Gerards S, Zweers H, de Boer W, Garbeva P Abstract There is increasing evidence that volatile organic compounds (VOCs) play an important role in the interactions between fungi and bacteria, two major groups of soil inhabiting microorganisms. Yet, most of the research has been focused on effects of bacterial volatiles on suppression of plant pathogenic fungi whereas little is known about the responses of bacteria to fungal volatiles. In the current study we performed a metabolomics analysis of volatiles emitted by several fungal and oomycetal soil strains under different nutrient conditions and growth stages. The metabolomics analysis of the tested fungal and oomycetal strains revealed different volatile profiles dependent on the age of the strains and nutrient conditions. Furthermore, we screened the phenotypic responses of soil bacterial strains to volatiles emitted by fungi. Two bacteria, Collimonas pratensis Ter291 and Serratia plymuthica PRI-2C, showed significant changes in their motility, in particular to volatiles emitted by Fusarium culmorum. This fungus produced a unique volatile blend, including several terpenes. Four of these terpenes were selected for further tests to investigate if they influence bacterial motility. Indeed, these terpenes induced or reduced swimming and swarming motility of S. plymuthica PRI-2C and swarming motility of C. pratensis Ter291, partly in a concentration-dependent manner. Overall the results of this work revealed that bacteria are able to sense and respond to fungal volatiles giving further evidence to the suggested importance of volatiles as signaling molecules in fungal-bacterial interactions. PMID: 26779150 [PubMed]

Lipoprotein hydrophobic core lipids are partially extruded to surface in smaller HDL: "Herniated" HDL, a common feature in diabetes. Sci Rep. 2016;6:19249 Authors: Amigó N, Mallol R, Heras M, Martínez-Hervás S, Blanco-Vaca F, Escolà-Gil JC, Plana N, Yanes Ó, Masana L, Correig X Abstract Recent studies have shown that pharmacological increases in HDL cholesterol concentrations do not necessarily translate into clinical benefits for patients, raising concerns about its predictive value for cardiovascular events. Here we hypothesize that the size-modulated lipid distribution within HDL particles is compromised in metabolic disorders that have abnormal HDL particle sizes, such as type 2 diabetes mellitus (DM2). By using NMR spectroscopy combined with a biochemical volumetric model we determined the size and spatial lipid distribution of HDL subclasses in a cohort of 26 controls and 29 DM2 patients before and after two drug treatments, one with niacin plus laropiprant and another with fenofibrate as an add-on to simvastatin. We further characterized the HDL surface properties using atomic force microscopy and fluorescent probes to show an abnormal lipid distribution within smaller HDL particles, a subclass particularly enriched in the DM2 patients. The reduction in the size, force cholesterol esters and triglycerides to emerge from the HDL core to the surface, making the outer surface of HDL more hydrophobic. Interestingly, pharmacological interventions had no effect on this undesired configuration, which may explain the lack of clinical benefits in DM2 subjects. PMID: 26778677 [PubMed - as supplied by publisher]

Infection and preterm birth. Semin Fetal Neonatal Med. 2016 Jan 6; Authors: Nadeau HC, Subramaniam A, Andrews WW Abstract Preterm birth (PTB) remains a primary cause of neonatal morbidity and mortality. The purpose of this article is to outline the association between infection and PTB. We performed a search of the PubMed database for relevant scientific work published in English from 1995 to July 2015. Whereas there is substantial evidence regarding infection as a strong risk factor for preterm birth, the role of specific bacterial and viral infections is not totally conclusive. Newer high-dimensional biological technologies such as microbiomics and metabolomics offer hope to identify the causative pathogens. In addition, strategies have been developed to reduce PTB. PMID: 26778525 [PubMed - as supplied by publisher]

Extra- and intracellular distribution of cytokinins in the leaves of monocots and dicots. N Biotechnol. 2016 Jan 8; Authors: Jiskrová E, Novák O, Pospíšilová H, Holubová K, Karády M, Galuszka P, Robert S, Frébort I Abstract The plant hormones cytokinins are a convenient target of genetic manipulations that bring benefits in biotechnological applications. The present work demonstrates the importance of the subcellular compartmentalization of cytokinins on the model dicot plant Arabidopsis thaliana and monocot crop Hordeum vulgare. The method of protoplast and vacuole isolation combined with precise cytokinin analysis and recovery assay of a vacuolar marker protein were used to quantify the contents of individual cytokinin forms in the leaf extracellular space, cell interior and vacuole. The data obtained for wild type plants and in each case a specific mutant line allow comparing the effect of genetic manipulations on the hormone distribution and homeostatic balance of cytokinins in the modified plants. PMID: 26777983 [PubMed - as supplied by publisher]

Matrix-assisted laser desorption/ionization mass spectrometry imaging of cell cultures for the lipidomic analysis of potential lipid markers in human breast cancer invasion. Rapid Commun Mass Spectrom. 2016 Feb 28;30(4):533-42 Authors: Wang S, Chen X, Luan H, Gao D, Lin S, Cai Z, Liu J, Liu H, Jiang Y Abstract RATIONALE: Breast cancer is the leading cause of cancer death among women worldwide. Identification of lipid targets that play a role in breast cancer invasion may advance our understanding of the rapid progression of cancer and may lead to the development of new biomarkers for the disease. METHODS: Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) was applied for the lipidomic profiling of two poorly invasive and two highly invasive breast cancer cell lines to identify the differentially accumulated lipids related to the invasive phenotype. The four cell lines were individually grown on indium tin oxide (ITO)-coated glass slides, analyzed as cell cultures. The raster width and matrix for detection were optimized to improve detection sensitivity. RESULTS: Optimized MSI measurements were performed directly on the cell culture with 9-aminoacridine as matrix, resulting in 215 endogenous compounds detected in positive ion mode and 267 endogenous compounds in negative ion mode in all the four cell lines, representing the largest group of analytes that have been analyzed from cells by a single MSI study. In highly invasive cell lines, 31 lipids including phosphatidylglycerol (PG) and phosphatidic acids were found upregulated and eight lipids including sphingomyelin (SM) downregulated in negative ion mode. The products of de novo fatty acid synthesis incorporated into membrane phospholipids, like oleic-acid-containing PG, may be involved in mitochondrial dysfunction and thus affect the invasion of breast cancer cells. The deficiency of SM may be related to the disruption of apoptosis in highly invasive cancer cells. CONCLUSIONS: This work uncovered more analytes in cells by MSI than previous reports, providing a better visualization and novel insights to advance our understanding of the relationship between rapid progression of breast cancer and lipid metabolism. The most altered lipids may aid the discovery of diagnostic markers and therapeutic targets of breast cancer. Copyright © 2016 John Wiley & Sons, Ltd. PMID: 26777684 [PubMed - in process]

ATM kinase: Much more than a DNA damage responsive protein. DNA Repair (Amst). 2015 Dec 29; Authors: Guleria A, Chandna S Abstract ATM, mutation of which causes Ataxia telangiectasia, has emerged as a cardinal multifunctional protein kinase during past two decades as evidenced by various studies from around the globe. Further to its well established and predominant role in DNA damage response, ATM has also been understood to help in maintaining overall functional integrity of cells; since its mutation, inactivation or deficiency results in a variety of pathological manifestations besides DNA damage. These include oxidative stress, metabolic syndrome, mitochondrial dysfunction as well as neurodegeneration. Recently, high throughput screening using proteomics, metabolomics and transcriptomic studies revealed several proteins which might be acting as substrates of ATM. Studies that can help in identifying effective regulatory controls within the ATM-mediated pathways/mechanisms can help in developing better therapeutics. In fact, more in-depth understanding of ATM-dependent cellular signals could also help in the treatment of variety of other disease conditions since these pathways seem to control many critical cellular functions. In this review, we have attempted to put together a detailed yet lucid picture of the present-day understanding of ATM's role in various pathophysiological conditions involving DNA damage and beyond. PMID: 26777338 [PubMed - as supplied by publisher]

Quantification of coffee blends for authentication of Asian palm civet coffee (Kopi Luwak) via metabolomics: A proof of concept. J Biosci Bioeng. 2016 Jan 5; Authors: Jumhawan U, Putri SP, Yusianto, Bamba T, Fukusaki E Abstract Asian palm civet coffee (Kopi Luwak), an animal-digested coffee with an exotic feature, carries a notorious reputation of being the rarest and most expensive coffee beverage in the world. Considering that illegal mixture of cheap coffee into civet coffee is a growing concern among consumers, we evaluated the use of metabolomics approach and orthogonal projection to latent structures (OPLS) prediction technique to quantify the degree of coffee adulteration. Two prediction sets, consisting of certified and commercial coffee, were made from a blend of civet and regular coffee with eleven mixing percentages. The prediction model exhibited accurate estimation of coffee blend percentage thus, successfully validating the prediction and quantification of the mixing composition of known-unknown samples. This work highlighted proof of concept of metabolomics application to predict degree of coffee adulteration by determining the civet coffee fraction in blends. PMID: 26777237 [PubMed - as supplied by publisher]

Genetic Variability Overrides the Impact of Parental Cell Type and Determines iPSC Differentiation Potential. Stem Cell Reports. 2016 Jan 12; Authors: Kyttälä A, Moraghebi R, Valensisi C, Kettunen J, Andrus C, Pasumarthy KK, Nakanishi M, Nishimura K, Ohtaka M, Weltner J, Van Handel B, Parkkonen O, Sinisalo J, Jalanko A, Hawkins RD, Woods NB, Otonkoski T, Trokovic R Abstract Reports on the retention of somatic cell memory in induced pluripotent stem cells (iPSCs) have complicated the selection of the optimal cell type for the generation of iPSC biobanks. To address this issue we compared transcriptomic, epigenetic, and differentiation propensities of genetically matched human iPSCs derived from fibroblasts and blood, two tissues of the most practical relevance for biobanking. Our results show that iPSC lines derived from the same donor are highly similar to each other. However, genetic variation imparts a donor-specific expression and methylation profile in reprogrammed cells that leads to variable functional capacities of iPSC lines. Our results suggest that integration-free, bona fide iPSC lines from fibroblasts and blood can be combined in repositories to form biobanks. Due to the impact of genetic variation on iPSC differentiation, biobanks should contain cells from large numbers of donors. PMID: 26777058 [PubMed - as supplied by publisher]

METABOLOMICS DIFFERENTIAL CORRELATION NETWORK ANALYSIS OF OSTEOARTHRITIS. Pac Symp Biocomput. 2016;21:120-31 Authors: Hu T, Zhang W, Fan Z, Sun G, Likhodi S, Randell E, Zhai G Abstract Osteoarthritis (OA) significantly compromises the life quality of affected individuals and imposes a substantial economic burden on our society. Unfortunately the pathogenesis of the disease is till poorly understood and no effective medications have been developed. OA is a complex disease that involves both genetic and environmental influences. To elucidate the complex interlinked structure of metabolic processes associated with OA, we developed a differential correlation network approach to detecting the interconnection of metabolite pairs whose relationships are significantly altered due to the diseased process. Through topological analysis of such a differential network, we identified key metabolites that played an important role in governing the connectivity and information flow of the network. Identification of these key metabolites suggests the association of their underlying cellular processes with OA and may help elucidate the pathogenesis of the disease and the development of novel targeted therapies. PMID: 26776179 [PubMed - in process]