Methods for interpreting lists of affected genes obstained in a DNA microarray experiment

Background - The aim of this paper was to describe and compare the methods used and the results obtained by the participants in a joint EADGENE (European Animal Disease Genomic Network of Excellence) and SABRE (Cutting Edge Genomics for Sustainable Animal Breeding) workshop focusing on post analysis of microarray data. The participating groups were provided with identical lists of microarray probes, including test statistics for three different contrasts, and the normalised log-ratios for each array, to be used as the starting point for interpreting the affected probes. The data originated from a microarray experiment conducted to study the host reactions in broilers occurring shortly after a secondary challenge with either a homologous or heterologous species of Eimeria. Results - Several conceptually different analytical approaches, using both commercial and public available software, were applied by the participating groups. The following tools were used: Ingenuity Pathway Analysis, MAPPFinder, LIMMA, GOstats, GOEAST, GOTM, Globaltest, TopGO, ArrayUnlock, Pathway Studio, GIST and AnnotationDbi. The main focus of the approaches was to utilise the relation between probes/genes and their gene ontology and pathways to interpret the affected probes/genes. The lack of a well-annotated chicken genome did though limit the possibilities to fully explore the tools. The main results from these analyses showed that the biological interpretation is highly dependent on the statistical method used but that some common biological conclusions could be reached. Conclusion - It is highly recommended to test different analytical methods on the same data set and compare the results to obtain a reliable biological interpretation of the affected genes in a DNA microarray experimen

Methods for interpreting lists of affected genes obtained in a DNA microarray experiment

BACKGROUND: The aim of this paper was to describe and compare the methods used and the results obtained by the participants in a joint EADGENE (European Animal Disease Genomic Network of Excellence) and SABRE (Cutting Edge Genomics for Sustainable Animal Breeding) workshop focusing on post analysis of microarray data. The participating groups were provided with identical lists of microarray probes, including test statistics for three different contrasts, and the normalised log-ratios for each array, to be used as the starting point for interpreting the affected probes. The data originated from a microarray experiment conducted to study the host reactions in broilers occurring shortly after a secondary challenge with either a homologous or heterologous species of Eimeria. RESULTS: Several conceptually different analytical approaches, using both commercial and public available software, were applied by the participating groups. The following tools were used: Ingenuity Pathway Analysis, MAPPFinder, LIMMA, GOstats, GOEAST, GOTM, Globaltest, TopGO, ArrayUnlock, Pathway Studio, GIST and AnnotationDbi. The main focus of the approaches was to utilise the relation between probes/genes and their gene ontology and pathways to interpret the affected probes/genes. The lack of a well-annotated chicken genome did though limit the possibilities to fully explore the tools. The main results from these analyses showed that the biological interpretation is highly dependent on the statistical method used but that some common biological conclusions could be reached. CONCLUSION: It is highly recommended to test different analytical methods on the same data set and compare the results to obtain a reliable biological interpretation of the affected genes in a DNA microarray experimen

Uncovering the multifaceted roles played by neutrophils in allogeneic hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a life-saving procedure used for the treatment of selected hematological malignancies, inborn errors of metabolism, and bone marrow failures. The role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against infection. However, recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered functions. Accordingly, neutrophils are emerging as highly versatile cells that are able to acquire different, often opposite, functional capacities depending on the microenvironment and their differentiation status. Herein, we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT, from the hematopoietic stem cell (HSC) mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC infusion. We also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versus-host disease (GVHD) prophylaxis. Finally, the potential involvement of neutrophils in alloHSCT-related complications, such as transplant-associated thrombotic microangiopathy (TA-TMA), acute and chronic GVHD, and cytomegalovirus (CMV) reactivation, is also discussed. Based on the data reviewed herein, the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial role. However, much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT

Carbon monoxide oxidation on nanostructured CuOx/CeO2 composite particles characterized by HREM, XPS, XAS, and high-energy diffraction

Nonstoichiometric CuO x /CeO 2 nanocomposite particles have been synthesized by inert gas condensation (IGC) over the whole compositional range (2 to 98 at.% Cu). The composition influences greatly the formation of various nanostructures, such as core-shells. A wide range of techniques were used to characterize the catalysts: high-resolution TEM and X-ray photoelectron spectroscopy, as well as high-energy diffraction (HED) and X-ray absorption spectroscopy (XANES and EXAFS) using synchrotron radiation. Catalytic oxidation of carbon monoxide was performed on catalysts with equal specific surface area, using both a batch reactor and a fixed-bed flow reactor. X-ray absorption spectroscopy showed that copper was present as a mixture of Cu(I) and Cu(II) species ranging from ca. 36% Cu(I) in one of the fresh samples to less than 5% in the activated samples. The coordination of Cu(I) was found to be mostly linear 2-coordinate as in the model compound Cu 2 O or alternatively 3-coordinate planar, while Cu(II) was found to present a mixture of tetrahedral and highly distorted octahedral coordination. EXAFS showed that both copper species were part of a very dispersed and highly disordered structure. The main chemical factors that control the activity for the oxidation of carbon monoxide are (i) the nanostructured morphology, (ii) the X-ray crystallinity as determined by HED, and (iii) the dispersion of copper at the surface. These three factors can be tailored during the IGC synthesis, but they can also change during the thermal activation. Copper ions migrate toward the particle surface and create new and highly dispersed superficial copper species/clusters, accompanied by a slight reduction of the CeO 2 surface. This favorable morphological evolution, or diminutive structural rearrangement, which was not adequately resolved by HREM, can be monitored as a shift of the light-off temperature. The wide variation in X-ray crystallinity between the catalysts can be used to quantify the processes occurring during the thermal activation. Easily reducible, high-energy surfaces of CeO 2 are better in stabilizing extremely dispersed copper species by a close synergistic interaction, which promotes a rapid change of valency and supply of oxygen. © 2002 Elsevier Science (USA).status: publishe

A hybrid cluster-lift method for the analysis of research activities

A hybrid of two novel methods - additive fuzzy spectral clustering and lifting method over a taxonomy - is applied to analyse the research activities of a department. To be specific, we concentrate on the Computer Sciences area represented by the ACM Computing Classification System (ACM-CCS), but the approach is applicable also to other taxonomies. Clusters of the taxonomy subjects are extracted using an original additive spectral clustering method involving a number of model-based stopping conditions. The clusters are parsimoniously lifted then to higher ranks of the taxonomy by minimizing the count of “head subjects” along with their “gaps” and “offshoots”. An example is given illustrating the method applied to real-world data

Constructing and mapping fuzzy thematic clusters to higher ranks in a taxonomy

We present a novel methodology for mapping a system such as a research department to a related taxonomy in a thematically consistent way. The components of the structure are supplied with fuzzy membership profiles over the taxonomy. Our method generalizes the profiles in two steps: first, by fuzzy clustering, and then by mapping the clusters to higher ranks of the taxonomy. To be specific, we concentrate on the Computer Sciences area represented by the taxonomy of ACM Computing Classification System (ACM-CCS). We build fuzzy clusters of the taxonomy leaves according to the similarity between individual profiles by using a novel, additive spectral, fuzzy clustering method that, in contrast to other methods, involves a number of model-based stopping conditions. The clusters are not necessarily consistent with the taxonomy. This is formalized by a novel method for parsimoniously elevating them to higher ranks of the taxonomy using an original recursive algorithm for minimizing a penalty function that involves “head subjects” on the higher ranks of the taxonomy along with their “gaps” and “offshoots”. An example is given illustrating the method applied to real-world data