Fatima Sanchez-Cabo - Academia.edu (original) (raw)

Papers by Fatima Sanchez-Cabo

Theranostics, 2017

One of the major limitations associated with platinum use is the resistance that almost invariabl... more One of the major limitations associated with platinum use is the resistance that almost invariably develops in different tumor types. In the current study, we sought to identify epigenetically regulated microRNAs as novel biomarkers of platinum resistance in lung and ovarian cancers, the ones with highest ratios of associated chemo-resistance. Methods: We combined transcriptomic data from microRNA and mRNA under the influence of an epigenetic reactivation treatment in a panel of four paired cisplatin -sensitive and -resistant cell lines, followed by real-time expression and epigenetic validations for accurate candidate selection in 19 human cancer cell lines. To identify specific candidate genes under miRNA regulation, we assembled "in silico" miRNAs and mRNAs sequences by using ten different algorithms followed by qRT-PCR validation. Functional assays of site-directed mutagenesis and luciferase activity, miRNAs precursor overexpression, silencing by antago-miR and cell vi...

Comparative and Functional Genomics, 2002

emphasized the role of statisticians in microarray technology and research. He pointed out that c... more emphasized the role of statisticians in microarray technology and research. He pointed out that cooperation between statisticians and biologists is useful and profitable for both sides. Although the number of purely statistical papers on microarray technology has grown exponentially, they are still in a minority compared to microarray-related biology papers.

eLife, 2014

Mesenchymal stem cells (MSCs) and osteolineage cells contribute to the hematopoietic stem cell (H... more Mesenchymal stem cells (MSCs) and osteolineage cells contribute to the hematopoietic stem cell (HSC) niche in the bone marrow of long bones. However, their developmental relationships remain unclear. In this study, we demonstrate that different MSC populations in the developing marrow of long bones have distinct functions. Proliferative mesoderm-derived nestin − MSCs participate in fetal skeletogenesis and lose MSC activity soon after birth. In contrast, quiescent neural crest-derived nestin + cells preserve MSC activity, but do not generate fetal chondrocytes. Instead, they differentiate into HSC niche-forming MSCs, helping to establish the HSC niche by secreting Cxcl12. Perineural migration of these cells to the bone marrow requires the ErbB3 receptor. The neonatal Nestin-GFP + Pdgfrα − cell population also contains Schwann cell precursors, but does not comprise mature Schwann cells. Thus, in the developing bone marrow HSC niche-forming MSCs share a common origin with sympathetic peripheral neurons and glial cells, and ontogenically distinct MSCs have non-overlapping functions in endochondrogenesis and HSC niche formation.

Comparative and Functional Genomics, 2002

Despite its enormous promise to further our understanding of cellular processes involved in the r... more Despite its enormous promise to further our understanding of cellular processes involved in the regulation of gene expression, microarray technology generates data for which statistical pre-processing has become a necessity before any interpretation of data can begin. The process by which we distinguish (and remove) non-biological variation from biological variation is called normalization. With a multitude of experimental designs, techniques and technologies influencing the acquisition of data, numerous approaches to normalization have been proposed in the literature. The purpose of this short review is not to add to the many suggestions that have been made, but to discuss some of the difficulties we encounter when analysing microarray data.

Comparative and Functional Genomics - COMPAR FUNCT GENOM, 2002

Despite its enormous promise to further our understanding of cellular processes involved in the r... more Despite its enormous promise to further our understanding of cellular processes involved in the regulation of gene expression, microarray technology generates data for which statistical pre-processing has become a necessity before any interpretation of data can begin. The process by which we distinguish (and remove) non-biological variation from biological variation is called normalization. With a multitude of experimental designs, techniques and technologies influencing the acquisition of data, numerous approaches to normalization have been proposed in the literature. The purpose of this short review is not to add to the many suggestions that have been made, but to discuss some of the difficulties we encounter when analysing microarray data.

Journal of Agricultural and Food Chemistry, 2013

Procyanidins modulate glucose metabolism, partly due to its effects on pancreas. Given the role o... more Procyanidins modulate glucose metabolism, partly due to its effects on pancreas. Given the role of microRNAs (miRNAs) in the regulation of diabetes and the fact that flavonoids modulate miRNAs in other tissues, we hypothesized that procyanidins might target miRNAs in the pancreas. We investigated the miRNA expression profile in pancreatic islets isolated from rats treated with a daily dose of grape seed procyanidin extract (GSPE) (25 mg/kg of body weight) for 45 days. The miRWalk database identified putative target genes of these miRNAs. We found that GSPE altered significantly the expression of miR-1249, miR-483, miR-30c-1*, and miR-3544. In silico prediction studies suggested that ion transport and response to glucose are among the regulated pathways. As a conclusion, this is the first study showing that procyanidins can also exert their bioactivity on pancreatic islets by modifying the miRNA expression pattern.

Molecular and Cellular Biology, 2005

Global inhibition of protein synthesis is a hallmark of many cellular stress conditions. Even tho... more Global inhibition of protein synthesis is a hallmark of many cellular stress conditions. Even though specific mRNAs defy this (e.g., yeast GCN4 and mammalian ATF4), the extent and variation of such resistance remain uncertain. In this study, we have identified yeast mRNAs that are translationally maintained following either amino acid depletion or fusel alcohol addition. Both stresses inhibit eukaryotic translation initiation factor 2B, but via different mechanisms. Using microarray analysis of polysome and monosome mRNA pools, we demonstrate that these stress conditions elicit widespread yet distinct translational reprogramming, identifying a fundamental role for translational control in the adaptation to environmental stress. These studies also highlight the complex interplay that exists between different stages in the gene expression pathway to allow specific preordained programs of proteome remodeling. For example, many ribosome biogenesis genes are coregulated at the transcriptional and translational levels following amino acid starvation. The transcriptional regulation of these genes has recently been connected to the regulation of cellular proliferation, and on the basis of our results, the translational control of these mRNAs should be factored into this equation.

Molecular Immunology, 2011

Molecular Immunology, 2011

Mitochondrion, 2011

The mitochondrial oxidative phosphorylation (OxPhos) system produces most of the ATP required by ... more The mitochondrial oxidative phosphorylation (OxPhos) system produces most of the ATP required by the cell. The structural proteins of the OxPhos holoenzymes are well known, but important aspects of their biogenesis and regulation remain to be uncovered and a significant fraction of mitochondrial proteins have yet to be identified. We have used a high throughput, genome-wide RNA interference (RNAi) approach to identify new OxPhos-related genes. We transduced a mouse fibroblast cell line with a lentiviral-based shRNA-library, and screened the cell population for growth impairment in galactose-based medium, which requires an intact OxPhos system. Candidate genes were ranked according to their co-expression with known genes encoding OxPhos mitochondria-located proteins. For the top ranking candidates the cellular process in which they are involved was evaluated. Our results show that the use of genome-wide RNAi together with screening for deficient growth in galactose medium is a suitable approach to identifying OxPhos-related and cellular energy metabolism-related genes. Interestingly also ubiquitin-proteasome related genes were selected.

Experientia, 2010

We have developed a method for reconstructing gene association networks and have applied this met... more We have developed a method for reconstructing gene association networks and have applied this method to gene profiles from 3T3-L1 cells. Priorization of the candidate genes pinpointed a transcript annotated as APMAP (adipocyte plasma membrane-associated protein). Functional studies showed that APMAP is upregulated in murine and human adipogenic cell models as well as in a genetic mouse model of obesity. Silencing APMAP in 3T3-L1 cells strongly impaired the differentiation into adipocytes. Moreover, APMAP expression was strongly induced by the PPARγ ligand rosiglitazone in adipocytes in vitro and in vivo in adipose tissue. Using ChIP-qPCR and luciferase reporter assays, we show a functional PPARγ binding site. In addition, we provide evidence that the extracellular C-terminal domain of APMAP is required for the function of APMAP in adipocyte differentiation. Finally, we demonstrate that APMAP translocates from the endoplasmatic reticulum to the plasma membrane during adipocyte differentiation.

BMC Genomics, 2010

Cancer progression is a complex process involving host-tumor interactions by multiple molecular a... more Cancer progression is a complex process involving host-tumor interactions by multiple molecular and cellular factors of the tumor microenvironment. Tumor cells that challenge immune activity may be vulnerable to immune destruction. To address this question we have directed major efforts towards data integration and developed and installed a database for cancer immunology with more than 1700 patients and associated clinical data and biomolecular data. Mining of the database revealed novel insights into the molecular mechanisms of tumor-immune cell interaction. In this paper we present the computational tools used to analyze integrated clinical and biomolecular data. Specifically, we describe a database for heterogenous data types, the interfacing bioinformatics and statistical tools including clustering methods, survival analysis, as well as visualization methods. Additionally, we discuss generic issues relevant to the integration of clinical and biomolecular data, as well as recent developments in integrative data analyses including biomolecular network reconstruction and mathematical modeling.

BMC bioinformatics, 2005

Background: Reconstructing regulatory networks from gene expression profiles is a challenging pro... more Background: Reconstructing regulatory networks from gene expression profiles is a challenging problem of functional genomics. In microarray studies the number of samples is often very limited compared to the number of genes, thus the use of discrete data may help reducing the probability of finding random associations between genes.

Science (New York, N.Y.), Jan 29, 2006

European Conference on Computational Biology, 2005

Motivation: With cDNA or oligonucleotide chips, gene-expression levels of essentially all genes i... more Motivation: With cDNA or oligonucleotide chips, gene-expression levels of essentially all genes in a genome can be simultaneously monitored over a time-course or under different experimental conditions. After proper normalization of the data, genes are often classified into co-expressed classes (clusters) to identify subgroups of genes that share common regulatory elements, a common function or a common cellular origin. With most methods, e.g. k -means, the number of clusters needs to be specified in advance; results depend strongly on this choice. Even with likelihood-based methods, estimation of this number is difficult. Furthermore, missing values often cause problems and lead to the loss of data. Results: We propose a fully probabilistic Bayesian model to cluster gene-expression profiles. The number of classes does not need to be specified in advance; instead it is adjusted dynamically using a Reversible Jump Markov Chain Monte Carlo sampler. Imputation of missing values is integrated into the model. With simulations, we determined the speed of convergence of the sampler as well as the accuracy of the inferred variables. Results were compared with the widely used kmeans algorithm. With our method, biologically related co-expressed genes could be identified in a yeast transcriptome dataset, even when some values were missing. Availability: The code is available at http://genome.tugraz.at/ BayesianClustering/

Methods in Molecular Biology, 2011

Transcriptomics has played an essential role as proof of concept in the development of experiment... more Transcriptomics has played an essential role as proof of concept in the development of experimental and bioinformatics approaches for the generation and analysis of Omics data. We are giving an introduction on how large-scale technologies for gene expression profiling, especially microarrays, have changed the view from studying single molecular events to a systems level view of global mechanisms in a cell, the biological processes, and their pathological mutations. The main platforms available for gene expression profiling (from microarrays to RNA-seq) are presented and the general concepts that need to be taken into account for proper data analysis in order to extract objective and general conclusions from transcriptomics experiments are introduced. We also describe the available main bioinformatics resources used for this purpose.

Nucleic Acids Research, 2006

Nucleic Acids Research, 2005

While generation of high-throughput expression data is becoming routine, the fast, easy, and syst... more While generation of high-throughput expression data is becoming routine, the fast, easy, and systematic presentation and analysis of these data in a biological context is still an obstacle. To address this need, we have developed PathwayExplorer, which maps expression profiles of genes or proteins simultaneously onto major, currently available regulatory, metabolic and cellular pathways from KEGG, BioCarta and GenMAPP. PathwayExplorer is a platform-independent web server application with an optional standalone Java application using a SOAP (simple object access protocol) interface. Mapped pathways are ranked for the easy selection of the pathway of interest, displaying all available genes of this pathway with their expression profiles in a selectable and intuitive color code. Pathway maps produced can be downloaded as PNG, JPG or as highresolution vector graphics SVG. The web service is freely available at https://pathwayexplorer.genome. tugraz.at; the standalone client can be downloaded at http://genome.tugraz.at.

Methods in Molecular Biology, 2011

In Omics experiments, typically thousands of hypotheses are tested simultaneously, each based on ... more In Omics experiments, typically thousands of hypotheses are tested simultaneously, each based on very few independent replicates. Traditional tests like the t-test were shown to perform poorly with this new type of data. Furthermore, simultaneous consideration of many hypotheses, each prone to a decision error, requires powerful adjustments for this multiple testing situation. After a general introduction to statistical testing, we present the moderated t-statistic, the SAM statistic, and the RankProduct statistic which have been developed to evaluate hypotheses in typical Omics experiments. We also provide an introduction to the multiple testing problem and discuss some state-of-the-art procedures to address this issue. The presented test statistics are subjected to a comparative analysis of a microarray experiment comparing tissue samples of two groups of tumors. All calculations can be done using the freely available statistical software R. Accompanying, commented code is available at: http://www.meduniwien.ac.at/msi/biometrie/MIMB.

Theranostics, 2017

One of the major limitations associated with platinum use is the resistance that almost invariabl... more One of the major limitations associated with platinum use is the resistance that almost invariably develops in different tumor types. In the current study, we sought to identify epigenetically regulated microRNAs as novel biomarkers of platinum resistance in lung and ovarian cancers, the ones with highest ratios of associated chemo-resistance. Methods: We combined transcriptomic data from microRNA and mRNA under the influence of an epigenetic reactivation treatment in a panel of four paired cisplatin -sensitive and -resistant cell lines, followed by real-time expression and epigenetic validations for accurate candidate selection in 19 human cancer cell lines. To identify specific candidate genes under miRNA regulation, we assembled "in silico" miRNAs and mRNAs sequences by using ten different algorithms followed by qRT-PCR validation. Functional assays of site-directed mutagenesis and luciferase activity, miRNAs precursor overexpression, silencing by antago-miR and cell vi...

Comparative and Functional Genomics, 2002

emphasized the role of statisticians in microarray technology and research. He pointed out that c... more emphasized the role of statisticians in microarray technology and research. He pointed out that cooperation between statisticians and biologists is useful and profitable for both sides. Although the number of purely statistical papers on microarray technology has grown exponentially, they are still in a minority compared to microarray-related biology papers.

eLife, 2014

Mesenchymal stem cells (MSCs) and osteolineage cells contribute to the hematopoietic stem cell (H... more Mesenchymal stem cells (MSCs) and osteolineage cells contribute to the hematopoietic stem cell (HSC) niche in the bone marrow of long bones. However, their developmental relationships remain unclear. In this study, we demonstrate that different MSC populations in the developing marrow of long bones have distinct functions. Proliferative mesoderm-derived nestin − MSCs participate in fetal skeletogenesis and lose MSC activity soon after birth. In contrast, quiescent neural crest-derived nestin + cells preserve MSC activity, but do not generate fetal chondrocytes. Instead, they differentiate into HSC niche-forming MSCs, helping to establish the HSC niche by secreting Cxcl12. Perineural migration of these cells to the bone marrow requires the ErbB3 receptor. The neonatal Nestin-GFP + Pdgfrα − cell population also contains Schwann cell precursors, but does not comprise mature Schwann cells. Thus, in the developing bone marrow HSC niche-forming MSCs share a common origin with sympathetic peripheral neurons and glial cells, and ontogenically distinct MSCs have non-overlapping functions in endochondrogenesis and HSC niche formation.

Comparative and Functional Genomics, 2002

Despite its enormous promise to further our understanding of cellular processes involved in the r... more Despite its enormous promise to further our understanding of cellular processes involved in the regulation of gene expression, microarray technology generates data for which statistical pre-processing has become a necessity before any interpretation of data can begin. The process by which we distinguish (and remove) non-biological variation from biological variation is called normalization. With a multitude of experimental designs, techniques and technologies influencing the acquisition of data, numerous approaches to normalization have been proposed in the literature. The purpose of this short review is not to add to the many suggestions that have been made, but to discuss some of the difficulties we encounter when analysing microarray data.

Comparative and Functional Genomics - COMPAR FUNCT GENOM, 2002

Despite its enormous promise to further our understanding of cellular processes involved in the r... more Despite its enormous promise to further our understanding of cellular processes involved in the regulation of gene expression, microarray technology generates data for which statistical pre-processing has become a necessity before any interpretation of data can begin. The process by which we distinguish (and remove) non-biological variation from biological variation is called normalization. With a multitude of experimental designs, techniques and technologies influencing the acquisition of data, numerous approaches to normalization have been proposed in the literature. The purpose of this short review is not to add to the many suggestions that have been made, but to discuss some of the difficulties we encounter when analysing microarray data.

Journal of Agricultural and Food Chemistry, 2013

Procyanidins modulate glucose metabolism, partly due to its effects on pancreas. Given the role o... more Procyanidins modulate glucose metabolism, partly due to its effects on pancreas. Given the role of microRNAs (miRNAs) in the regulation of diabetes and the fact that flavonoids modulate miRNAs in other tissues, we hypothesized that procyanidins might target miRNAs in the pancreas. We investigated the miRNA expression profile in pancreatic islets isolated from rats treated with a daily dose of grape seed procyanidin extract (GSPE) (25 mg/kg of body weight) for 45 days. The miRWalk database identified putative target genes of these miRNAs. We found that GSPE altered significantly the expression of miR-1249, miR-483, miR-30c-1*, and miR-3544. In silico prediction studies suggested that ion transport and response to glucose are among the regulated pathways. As a conclusion, this is the first study showing that procyanidins can also exert their bioactivity on pancreatic islets by modifying the miRNA expression pattern.

Molecular and Cellular Biology, 2005

Global inhibition of protein synthesis is a hallmark of many cellular stress conditions. Even tho... more Global inhibition of protein synthesis is a hallmark of many cellular stress conditions. Even though specific mRNAs defy this (e.g., yeast GCN4 and mammalian ATF4), the extent and variation of such resistance remain uncertain. In this study, we have identified yeast mRNAs that are translationally maintained following either amino acid depletion or fusel alcohol addition. Both stresses inhibit eukaryotic translation initiation factor 2B, but via different mechanisms. Using microarray analysis of polysome and monosome mRNA pools, we demonstrate that these stress conditions elicit widespread yet distinct translational reprogramming, identifying a fundamental role for translational control in the adaptation to environmental stress. These studies also highlight the complex interplay that exists between different stages in the gene expression pathway to allow specific preordained programs of proteome remodeling. For example, many ribosome biogenesis genes are coregulated at the transcriptional and translational levels following amino acid starvation. The transcriptional regulation of these genes has recently been connected to the regulation of cellular proliferation, and on the basis of our results, the translational control of these mRNAs should be factored into this equation.

Molecular Immunology, 2011

Molecular Immunology, 2011

Mitochondrion, 2011

The mitochondrial oxidative phosphorylation (OxPhos) system produces most of the ATP required by ... more The mitochondrial oxidative phosphorylation (OxPhos) system produces most of the ATP required by the cell. The structural proteins of the OxPhos holoenzymes are well known, but important aspects of their biogenesis and regulation remain to be uncovered and a significant fraction of mitochondrial proteins have yet to be identified. We have used a high throughput, genome-wide RNA interference (RNAi) approach to identify new OxPhos-related genes. We transduced a mouse fibroblast cell line with a lentiviral-based shRNA-library, and screened the cell population for growth impairment in galactose-based medium, which requires an intact OxPhos system. Candidate genes were ranked according to their co-expression with known genes encoding OxPhos mitochondria-located proteins. For the top ranking candidates the cellular process in which they are involved was evaluated. Our results show that the use of genome-wide RNAi together with screening for deficient growth in galactose medium is a suitable approach to identifying OxPhos-related and cellular energy metabolism-related genes. Interestingly also ubiquitin-proteasome related genes were selected.

Experientia, 2010

We have developed a method for reconstructing gene association networks and have applied this met... more We have developed a method for reconstructing gene association networks and have applied this method to gene profiles from 3T3-L1 cells. Priorization of the candidate genes pinpointed a transcript annotated as APMAP (adipocyte plasma membrane-associated protein). Functional studies showed that APMAP is upregulated in murine and human adipogenic cell models as well as in a genetic mouse model of obesity. Silencing APMAP in 3T3-L1 cells strongly impaired the differentiation into adipocytes. Moreover, APMAP expression was strongly induced by the PPARγ ligand rosiglitazone in adipocytes in vitro and in vivo in adipose tissue. Using ChIP-qPCR and luciferase reporter assays, we show a functional PPARγ binding site. In addition, we provide evidence that the extracellular C-terminal domain of APMAP is required for the function of APMAP in adipocyte differentiation. Finally, we demonstrate that APMAP translocates from the endoplasmatic reticulum to the plasma membrane during adipocyte differentiation.

BMC Genomics, 2010

Cancer progression is a complex process involving host-tumor interactions by multiple molecular a... more Cancer progression is a complex process involving host-tumor interactions by multiple molecular and cellular factors of the tumor microenvironment. Tumor cells that challenge immune activity may be vulnerable to immune destruction. To address this question we have directed major efforts towards data integration and developed and installed a database for cancer immunology with more than 1700 patients and associated clinical data and biomolecular data. Mining of the database revealed novel insights into the molecular mechanisms of tumor-immune cell interaction. In this paper we present the computational tools used to analyze integrated clinical and biomolecular data. Specifically, we describe a database for heterogenous data types, the interfacing bioinformatics and statistical tools including clustering methods, survival analysis, as well as visualization methods. Additionally, we discuss generic issues relevant to the integration of clinical and biomolecular data, as well as recent developments in integrative data analyses including biomolecular network reconstruction and mathematical modeling.

BMC bioinformatics, 2005

Background: Reconstructing regulatory networks from gene expression profiles is a challenging pro... more Background: Reconstructing regulatory networks from gene expression profiles is a challenging problem of functional genomics. In microarray studies the number of samples is often very limited compared to the number of genes, thus the use of discrete data may help reducing the probability of finding random associations between genes.

Science (New York, N.Y.), Jan 29, 2006

European Conference on Computational Biology, 2005

Motivation: With cDNA or oligonucleotide chips, gene-expression levels of essentially all genes i... more Motivation: With cDNA or oligonucleotide chips, gene-expression levels of essentially all genes in a genome can be simultaneously monitored over a time-course or under different experimental conditions. After proper normalization of the data, genes are often classified into co-expressed classes (clusters) to identify subgroups of genes that share common regulatory elements, a common function or a common cellular origin. With most methods, e.g. k -means, the number of clusters needs to be specified in advance; results depend strongly on this choice. Even with likelihood-based methods, estimation of this number is difficult. Furthermore, missing values often cause problems and lead to the loss of data. Results: We propose a fully probabilistic Bayesian model to cluster gene-expression profiles. The number of classes does not need to be specified in advance; instead it is adjusted dynamically using a Reversible Jump Markov Chain Monte Carlo sampler. Imputation of missing values is integrated into the model. With simulations, we determined the speed of convergence of the sampler as well as the accuracy of the inferred variables. Results were compared with the widely used kmeans algorithm. With our method, biologically related co-expressed genes could be identified in a yeast transcriptome dataset, even when some values were missing. Availability: The code is available at http://genome.tugraz.at/ BayesianClustering/

Methods in Molecular Biology, 2011

Transcriptomics has played an essential role as proof of concept in the development of experiment... more Transcriptomics has played an essential role as proof of concept in the development of experimental and bioinformatics approaches for the generation and analysis of Omics data. We are giving an introduction on how large-scale technologies for gene expression profiling, especially microarrays, have changed the view from studying single molecular events to a systems level view of global mechanisms in a cell, the biological processes, and their pathological mutations. The main platforms available for gene expression profiling (from microarrays to RNA-seq) are presented and the general concepts that need to be taken into account for proper data analysis in order to extract objective and general conclusions from transcriptomics experiments are introduced. We also describe the available main bioinformatics resources used for this purpose.

Nucleic Acids Research, 2006

Nucleic Acids Research, 2005

While generation of high-throughput expression data is becoming routine, the fast, easy, and syst... more While generation of high-throughput expression data is becoming routine, the fast, easy, and systematic presentation and analysis of these data in a biological context is still an obstacle. To address this need, we have developed PathwayExplorer, which maps expression profiles of genes or proteins simultaneously onto major, currently available regulatory, metabolic and cellular pathways from KEGG, BioCarta and GenMAPP. PathwayExplorer is a platform-independent web server application with an optional standalone Java application using a SOAP (simple object access protocol) interface. Mapped pathways are ranked for the easy selection of the pathway of interest, displaying all available genes of this pathway with their expression profiles in a selectable and intuitive color code. Pathway maps produced can be downloaded as PNG, JPG or as highresolution vector graphics SVG. The web service is freely available at https://pathwayexplorer.genome. tugraz.at; the standalone client can be downloaded at http://genome.tugraz.at.

Methods in Molecular Biology, 2011

In Omics experiments, typically thousands of hypotheses are tested simultaneously, each based on ... more In Omics experiments, typically thousands of hypotheses are tested simultaneously, each based on very few independent replicates. Traditional tests like the t-test were shown to perform poorly with this new type of data. Furthermore, simultaneous consideration of many hypotheses, each prone to a decision error, requires powerful adjustments for this multiple testing situation. After a general introduction to statistical testing, we present the moderated t-statistic, the SAM statistic, and the RankProduct statistic which have been developed to evaluate hypotheses in typical Omics experiments. We also provide an introduction to the multiple testing problem and discuss some state-of-the-art procedures to address this issue. The presented test statistics are subjected to a comparative analysis of a microarray experiment comparing tissue samples of two groups of tumors. All calculations can be done using the freely available statistical software R. Accompanying, commented code is available at: http://www.meduniwien.ac.at/msi/biometrie/MIMB.