Gene network inference and visualization tools for biologists: application to new human transcriptome datasets

Hurley, Daniel; Araki, Hiromitsu; Tamada, Yoshinori; Dunmore, Ben; Sanders, Deborah A.; Humphreys, Sally; Affara, Muna; Imoto, Seiya; Yasuda, Kaori; Tomiyasu, Yuki; Tashiro, Kosuke; Savoie, Christopher J.; Cho, Vicky; Smith, Stephen K.; Kuhara, Satoru; Miyano, Satoru; Charnock-Jones, D. Stephen; Crampin, Edmund J.; Print, Cristin G.

doi:10.1093/nar/gkr902

Cited by 74 publications

(80 citation statements)

References 66 publications

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“…Examples of such methods include principal component analysis (PCA) and hierarchical clustering (HC) to identify potentially co-expressed genes over the different combinatorial growth conditions. In addition, Bayesian network (BN) analysis can be used to infer regulatory linkages between mRNA abundances (Friedman, 2004;Hurley et al, 2012;Sachs et al, 2005;Yu et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic analysis reveals how a lack of potassium ions increases Sulfolobus acidocaldarius sensitivity to pH changes

et al. 2016

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Extremely acidophilic microorganisms (optimum growth pH of 3) maintain a near neutral cytoplasmic pH via several homeostatic mechanisms, including an inside positive membrane potential created by potassium ions. Transcriptomic responses to pH stress in the thermoacidophilic archaeon, Sulfolobus acidocaldarius were investigated by growing cells without added sodium and/or potassium ions at both optimal and sub-optimal pH. Culturing the cells in the absence of added sodium or potassium ions resulted in a reduced growth rate compared to full-salt conditions as well as 43 and 75 significantly different RNA transcript ratios, respectively. Differentially expressed RNA transcripts during growth in the absence of added sodium ions included genes coding for permeases, a sodium/proline transporter and electron transport proteins. In contrast, culturing without added potassium ions resulted in higher RNA transcripts for similar genes as a lack of sodium ions plus genes related to spermidine that has a general role in response to stress and a decarboxylase that potentially consumes protons. The greatest RNA transcript response occurred when S. acidocaldarius cells were grown in the absence of potassium and/or sodium at a sub-optimal pH. These adaptations included those listed above plus osmoregulated glucans and mechanosensitive channels that have previously been shown to respond to osmotic stress. In addition, data analyses revealed two co-expressed IclR family transcriptional regulator genes with a previously unknown role in the S. acidocaldarius pH stress response. Our study provides additional evidence towards the importance of potassium in acidophile growth at acidic pH.

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Section: Introductionmentioning

confidence: 99%

Transcriptomic analysis reveals how a lack of potassium ions increases Sulfolobus acidocaldarius sensitivity to pH changes

et al. 2016

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“…However, our data suggest a different regulatory role for PI3K/FOXO1A in differentiating ESC and ESC-derived endothelial cells where FOXO1A has a mainly inhibitory feedback signal. We characterized the temporal expression of FOXO1A and angiopoietin2, one of the FOXO1A target genes [32][33][34] and related to angiogenesis and vascular remodeling, during in vivo differentiation and maturation of hESC-EC. Three weeks after transplantation of hESC-EC into athymic nude rats, cells showed engraftment and were detectable with histology.…”

Section: Discussionmentioning

confidence: 99%

Signaling Via PI3K/FOXO1A Pathway Modulates Formation and Survival of Human Embryonic Stem Cell-Derived Endothelial Cells

Merkely

Gara

Lendvai

et al. 2015

Stem Cells and Development

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“…Thus, the works [307][308][309][310][311] report network inference results obtained with datasets with missing values. Wu et al [307] presented a network inference method with an interpolation controller, providing three selections of data interpolation approaches.…”

Section: Introductionmentioning

confidence: 99%

“…In [308,309] MD is handled with a weighted k-nearest neighbor method. Hurley et al [311] illustrated the use of a suite of gene GRN analysis tools imputing MD using the LSImpute missing value estimation method. It should be noted that the aforementioned methods [307][308][309]311] are specific for GRN inference with gene expression data, and the approaches chosen to handle MD are not justified nor compared to other alternatives.…”

Section: Introductionmentioning

confidence: 99%

“…Hurley et al [311] illustrated the use of a suite of gene GRN analysis tools imputing MD using the LSImpute missing value estimation method. It should be noted that the aforementioned methods [307][308][309]311] are specific for GRN inference with gene expression data, and the approaches chosen to handle MD are not justified nor compared to other alternatives. In [310] a network inference tool designed for GRNs, NetGenerator, is extended in several ways in order to predict pathogen-host interactions.…”

Section: Introductionmentioning

confidence: 99%

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Chemometric Approaches for Systems Biology

Fortuny¹

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The present Ph.D. thesis is devoted to study, develop and apply approaches commonly used in chemometrics to the emerging field of systems biology. Existing procedures and new methods are applied to solve research and industrial questions in different multidisciplinary teams. The methodologies developed in this document will enrich the plethora of procedures employed within omic sciences to understand biological organisms and will improve processes in biotechnological industries integrating biological knowledge at different levels and exploiting the software packages derived from the thesis.This dissertation is structured in four parts. The first block describes the framework in which the contributions presented here are based. The objectives of the two research projects related to this thesis are highlighted and the specific topics addressed in this document via conference presentations and research articles are introduced. A comprehensive description of omic sciences and their relationships within the systems biology paradigm is given in this part, jointly with a review of the most applied multivariate methods in chemometrics, on which the novel approaches proposed here are founded.The second part addresses many problems of data understanding within metabolomics, fluxomics, proteomics and genomics. Different alternatives are proposed in this block to understand flux data in steady state conditions. Some are based on applications of multivariate methods previously applied in other chemometrics areas. Others are novel approaches based on a bilinear decomposition using elemental metabolic pathways, from which a GNU licensed toolbox is made freely available for the scientific community. As well, a framework for metabolic data understanding is proposed for non-steady state data, using the same bilinear decomposition proposed for steady state data, but modelling the dynamics of the experiments using novel two and three-way data analysis procedures. Also, the relationships between different omic levels are assessed in this part integrating different sources of information of plant viruses in data fusion models. Finally, an example of interaction between organisms, oranges and fungi, is studied via multivariate image analysis techniques, with future application in food industries.v The third block of this thesis is a thoroughly study of different missing data problems related to chemometrics, systems biology and industrial bioprocesses. In the theoretical chapters of this part, new algorithms to obtain multivariate exploratory and regression models in the presence of missing data are proposed, which serve also as preprocessing steps of any other methodology used by practitioners. Regarding applications, this block explores the reconstruction of networks in omic sciences when missing and faulty measurements appear in databases, and how calibration models between near infrared instruments can be transferred, avoiding costs and time-consuming full recalibrations in bioindustries and research laboratories. Finally,...

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Gene network inference and visualization tools for biologists: application to new human transcriptome datasets

Cited by 74 publications

References 66 publications

Transcriptomic analysis reveals how a lack of potassium ions increases Sulfolobus acidocaldarius sensitivity to pH changes

Transcriptomic analysis reveals how a lack of potassium ions increases Sulfolobus acidocaldarius sensitivity to pH changes

Signaling Via PI3K/FOXO1A Pathway Modulates Formation and Survival of Human Embryonic Stem Cell-Derived Endothelial Cells

Chemometric Approaches for Systems Biology

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