bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addressing the Challenge of Defining Valid Proteomic Biomarkers and Classifiers
Authors: Dakna Mohammed , Harris Keith , Kalousis Alexandros , Carpentier Sebastien , Kolch Walter , Schanstra Joost P , Haubitz Marion , Vlahou Antonia , Mischak Harald , Girolami Mark 
Published: January 2011

Abstract

Background
The purpose of this manuscript is to provide, based on an extensive analysis of a proteomic data set, suggestions for proper statistical analysis for the discovery of sets of clinically relevant biomarkers. As tractable example we define the measurable proteomic differences between apparently healthy adult males and females. We choose urine as body-fluid of interest and CE-MS, a thoroughly validated platform technology, allowing for routine analysis of a large number of samples. The second urine of the morning was collected from apparently healthy male and female volunteers (aged 21-40) in the course of the routine medical check-up before recruitment at the Hannover Medical School.

Results
We found that the Wilcoxon-test is best suited for the definition of potential biomarkers. Adjustment for multiple testing is necessary. Sample size estimation can be performed based on a small number of observations via resampling from pilot data. Machine learning algorithms appear ideally suited to generate classifiers. Assessment of any results in an independent test-set is essential.

Conclusions
Valid proteomic biomarkers for diagnosis and prognosis only can be defined by applying proper statistical data mining procedures. In particular, a justification of the sample size should be part of the study design.
Initial steps towards a production platform for DNA sequence analysis on the grid
Authors: Luyf Angela CM , van Schaik Barbera DC , de Vries Michel , Baas Frank , van Kampen Antoine HC , Olabarriaga Silvia D 
Published: January 2011

AbstractBackgroundBioinformatics is confronted with a new data explosion due to the availability of high throughput DNA sequencers. Data storage and analysis becomes a problem on local servers, and therefore it is needed to switch to other IT infrastructures. Grid and workflow technology can help to handle the data more efficiently, as well as facilitate collaborations. However, interfaces to grids are often unfriendly to novice users.ResultsIn this study we reused a platform that was developed in the VL-e project for the analysis of medical images. Data transfer, workflow execution and job monitoring are operated from one graphical interface. We developed workflows for two sequence alignment tools (BLAST and BLAT) as a proof of concept. The analysis time was significantly reduced. All workflows and executables are available for the members of the Dutch Life Science Grid and the VL-e Medical virtual organizations All components are open source and can be transported to other grid infrastructures.ConclusionsThe availability of in-house expertise and tools facilitates the usage of grid resources by new users. Our first results indicate that this is a practical, powerful and scalable solution to address the capacity and collaboration issues raised by the deployment of next generation sequencers. We currently adopt this methodology on a daily basis for DNA sequencing and other applications. More information and source code is available viahttp://www.bioinformaticslaboratory.nl/
Content-based microarray search using differential expression profiles
Authors: Engreitz Jesse M , Morgan Alexander A , Dudley Joel T , Chen Rong , Thathoo Rahul , Altman Russ B , Butte Atul J 
Published: January 2011

AbstractBackgroundWith the expansion of public repositories such as the Gene Expression Omnibus (GEO), we are rapidly cataloging cellular transcriptional responses to diverse experimental conditions. Methods that query these repositories based on gene expression content, rather than textual annotations, may enable more effective experiment retrieval as well as the discovery of novel associations between drugs, diseases, and other perturbations.ResultsWe develop methods to retrieve gene expression experiments that differentially express the same transcriptional programs as a query experiment. Avoiding thresholds, we generate differential expression profiles that include a score for each gene measured in an experiment. We use existing and novel dimension reduction and correlation measures to rank relevant experiments in an entirely data-driven manner, allowing emergent features of the data to drive the results. A combination of matrix decomposition andp-weighted Pearson correlation proves the most suitable for comparing differential expression profiles. We apply this method to index all GEO DataSets, and demonstrate the utility of our approach by identifying pathways and conditions relevant to transcription factors Nanog and FoxO3.ConclusionsContent-based gene expression search generates relevant hypotheses for biological inquiry. Experiments across platforms, tissue types, and protocols inform the analysis of new datasets.
CNV-WebStore: Online CNV Analysis, Storage and Interpretation
Authors: Vandeweyer Geert , Reyniers Edwin , Wuyts Wim , Rooms Liesbeth , Kooy R Frank 
Published: January 2011

Abstract

Background
Microarray technology allows the analysis of genomic aberrations at an ever increasing resolution, making functional interpretation of these vast amounts of data the main bottleneck in routine implementation of high resolution array platforms, and emphasising the need for a centralised and easy to use CNV data management and interpretation system.

Results
We present CNV-WebStore, an online platform to streamline the processing and downstream interpretation of microarray data in a clinical context, tailored towards but not limited to the Illumina BeadArray platform. Provided analysis tools include CNV analsyis, parent of origin and uniparental disomy detection. Interpretation tools include data visualisation, gene prioritisation, automated PubMed searching, linking data to several genome browsers and annotation of CNVs based on several public databases. Finally a module is provided for uniform reporting of results.

Conclusion
CNV-WebStore is able to present copy number data in an intuitive way to both lab technicians and clinicians, making it a useful tool in daily clinical practice.
Ligands specify estrogen receptor alpha nuclear localization and degradation
Authors: Kocanova Silvia , Mazaheri Mahta , Caze-Subra Stéphanie , Bystricky Kerstin 
Published: January 2011

AbstractBackgroundThe estrogen receptor alpha (ERα) is found predominately in the nucleus, both in hormone stimulated and untreated cells. Intracellular distribution of the ERα changes in the presence of agonists but the impact of different antiestrogens on the fate of ERα is a matter of debate.ResultsA MCF-7 cell line stably expressing GFP-tagged human ERα (SK19 cell line) was created to examine the localization of ligand-bound GFP-ERα. We combined digitonin-based cell fractionation analyses with fluorescence and immuno-electron microscopy to determine the intracellular distribution of ligand-bound ERα and/or GFP-ERα.Using fluorescence- and electron microscopy we demonstrate that both endogenous ERα and GFP-ERα form numerous nuclear focal accumulations upon addition of agonist, 17β-estradiol (E2), and pure antagonists (selective estrogen regulator disruptor; SERD), ICI 182,780 or RU58,668, while in the presence of partial antagonists (selective estrogen regulator modulator; SERM), 4-hydroxytamoxifen (OHT) or RU39,411, diffuse nuclear staining persisted.Digitonin based cell fractionation analyses confirmed that endogenous ERα and GFP-ERα predominantly reside in the nuclear fraction. Overall ERα protein levels were reduced after estradiol treatment. In the presence of SERMs ERα was stabilized in the nuclear soluble fraction, while in the presence of SERDs protein levels decreased drastically and the remaining ERα was largely found in a nuclear insoluble fraction. mRNA levels ofESR1were reduced compared to untreated cells in the presence of all ligands tested, including E2. E2 and SERDs induced ERα degradation occurred in distinct nuclear foci composed of ERα and the proteasome providing a simple explanation for ERα sequestration in the nucleus.ConclusionsOur results indicate that chemical structure of ligands directly affect the nuclear fate and protein turnover of the estrogen receptor alpha independently of their impact on transcription. These findings provide a molecular basis for the selection of antiestrogen compounds issue from pharmacological studies aimed at improving treatment of breast cancer.
Molecular dissection of the migrating posterior lateral line primordium during early development in zebrafish
Authors: Gallardo Viviana E , Liang Jin , Behra Martine , Elkahloun Abdel , Villablanca Eduardo J , Russo Vincenzo , Allende Miguel L , Burgess Shawn M 
Published: January 2011

AbstractBackgroundDevelopment of the posterior lateral line (PLL) system in zebrafish involves cell migration, proliferation and differentiation of mechanosensory cells. The PLL forms when cranial placodal cells delaminate and become a coherent, migratory primordium that traverses the length of the fish to form this sensory system. As it migrates, the primordium deposits groups of cells called neuromasts, the specialized organs that contain the mechanosensory hair cells. Therefore the primordium provides both a model for studying collective directional cell migration and the differentiation of sensory cells from multipotent progenitor cells.ResultsThrough the combined use of transgenic fish, Fluorescence Activated Cell Sorting and microarray analysis we identified a repertoire of key genes expressed in the migrating primordium and in differentiated neuromasts. We validated the specific expression in the primordium of a subset of the identified sequences by quantitative RT-PCR, and byin situhybridization. We also show that interfering with the function of two genes,f11randcd9b, defects in primordium migration are induced. Finally, pathway construction revealed functional relationships among the genes enriched in the migrating cell population.ConclusionsOur results demonstrate that this is a robust approach to globally analyze tissue-specific expression and we predict that many of the genes identified in this study will show critical functions in developmental events involving collective cell migration and possibly in pathological situations such as tumor metastasis.
Next generation sequencing and analysis of a conserved transcriptome of New Zealand's kiwi
Authors: Subramanian Sankar , Huynen Leon , Millar Craig D , Lambert David M 
Published: January 2011

Abstract

Background
Kiwi is a highly distinctive, flightless and endangered ratite bird endemic to New Zealand. To understand the patterns of molecular evolution of the nuclear protein-coding genes in brown kiwi (Apteryx australis mantelli) and to determine the timescale of avian history we sequenced a transcriptome obtained from a kiwi embryo using next generation sequencing methods. We then assembled the conserved protein-coding regions using the chicken proteome as a scaffold.

Results
Using 1,543 conserved protein coding genes we estimated the neutral evolutionary divergence between the kiwi and chicken to be ~45%, which is approximately equal to the divergence computed for the human-mouse pair using the same set of genes. A large fraction of genes was found to be under high selective constraint, as most of the expressed genes appeared to be involved in developmental gene regulation. Our study suggests a significant relationship between gene expression levels and protein evolution. Using sequences from over 700 nuclear genes we estimated the divergence between the two basal avian groups, Palaeognathae and Neognathae to be 132 million years, which is consistent with previous studies using mitochondrial genes.

Conclusions
The results of this investigation revealed patterns of mutation and purifying selection in conserved protein coding regions in birds. Furthermore this study suggests a relatively cost-effective way of obtaining a glimpse into the fundamental molecular evolutionary attributes of a genome, particularly when no closely related genomic sequence is available.
The relationship between the error catastrophe, survival of the flattest, and natural selection
Authors: Tejero Héctor , Marín Arturo , Montero Francisco 
Published: January 2011

Abstract

Background
The quasispecies model is a general model of evolution that is generally applicable to replication up to high mutation rates. It predicts that at a sufficiently high mutation rate, quasispecies with higher mutational robustness can displace quasispecies with higher replicative capacity, a phenomenon called "survival of the flattest". In some fitness landscapes it also predicts the existence of a maximum mutation rate, called the error threshold, beyond which the quasispecies enters into error catastrophe, losing its genetic information. The aim of this paper is to study the relationship between survival of the flattest and the transition to error catastrophe, as well as the connection between these concepts and natural selection.

Results
By means of a very simplified model, we show that the transition to an error catastrophe corresponds to a value of zero for the selective coefficient of the mutant phenotype with respect to the master phenotype, indicating that transition to the error catastrophe is in this case similar to the selection of a more robust species. This correspondence has been confirmed by considering a single-peak landscape in which sequences are grouped with respect to their Hamming distant from the master sequence. When the robustness of a classe is changed by modification of its quality factor, the distribution of the population changes in accordance with the new value of the robustness, although an error catastrophe can be detected at the same values as in the general case. When two quasispecies of different robustness competes with one another, the entry of one of them into error catastrophe causes displacement of the other, because of the greater robustness of the former. Previous works are explicitly reinterpreted in the light of the results obtained in this paper.

Conclusions
The main conclusion of this paper is that the entry into error catastrophe is a specific case of survival of the flattest acting on phenotypes that differ in the trade-off between replicative ability and mutational robustness. In fact, entry into error catastrophe occurs when the mutant phenotype acquires a selective advantage over the master phenotype. As both entry into error catastrophe and survival of the flattest are caused by natural selection when mutation rate is increased, we propose differentiating between them by the level of selection at which natural selection acts. So we propose to consider the transition to error catastrophe as a phenomenon of intra-quasispecies selection, and survival of the flattest as a phenomenon of inter-quasispecies selection.
Regulatory polymorphisms in the bovine Ankyrin 1 gene promoter are associated with tenderness and intramuscular fat content
Authors: Aslan Ozlem , Sweeney Torres , Mullen Anne Maria , Hamill Ruth M 
Published: January 2011

Abstract

Background
Recent QTL and gene expression studies have highlighted ankyrins as positional and functional candidate genes for meat quality. Our objective was to characterise the promoter region of the bovine ankyrin 1 gene and to test polymorphisms for association with sensory and technological meat quality measures.

Results
Seven novel promoter SNPs were identified in a 1.11 kb region of the ankyrin 1 promoter in Angus, Charolais and Limousin bulls (n = 15 per breed) as well as 141 crossbred beef animals for which meat quality data was available. Eighteen haplotypes were inferred with significant breed variation in haplotype frequencies. The five most frequent SNPs and the four most frequent haplotypes were subsequently tested for association with sensory and technological measures of meat quality in the crossbred population. SNP1, SNP3 and SNP4 (which were subsequently designated regulatory SNPs) and SNP5 were associated with traits that contribute to sensorial and technological measurements of tenderness and texture; Haplotype 1 and haplotype 4 were oppositely correlated with traits contributing to tenderness (P < 0.05). While no single SNP was associated with intramuscular fat (IMF), a clear association with increased IMF and juiciness was observed for haplotype 2.

Conclusion
The conclusion from this study is that alleles defining haplotypes 2 and 4 could usefully contribute to marker SNP panels used to select individuals with improved IMF/juiciness or tenderness in a genome-assisted selection framework.
Recent transfer of an iron-regulated gene from the plastid to the nuclear genome in an oceanic diatom adapted to chronic iron limitation
Authors: Lommer Markus , Roy Alexandra-Sophie , Schilhabel Markus , Schreiber Stefan , Rosenstiel Philip , LaRoche Julie 
Published: January 2011

AbstractBackgroundAlthough the importance and widespread occurrence of iron limitation in the contemporary ocean is well documented, we still know relatively little about genetic adaptation of phytoplankton to these environments. Compared to its coastal relativeThalassiosira pseudonana, the oceanic diatomThalassiosira oceanicais highly tolerant to iron limitation. The adaptation to low-iron conditions inT. oceanicahas been attributed to a decrease in the photosynthetic components that are rich in iron. Genomic information onT. oceanicamay shed light on the genetic basis of the physiological differences between the two species.ResultsThe complete 141790 bp sequence of theT. oceanicachloroplast genome [GenBank: GU323224], assembled from massively parallel pyrosequencing (454) shotgun reads, revealed that thepetFgene encoding for ferredoxin, which is localized in the chloroplast genome inT. pseudonanaand other diatoms, has been transferred to the nucleus inT. oceanica. The iron-sulfur protein ferredoxin, a key element of the chloroplast electron transport chain, can be replaced by the iron-free flavodoxin under iron-limited growth conditions thereby contributing to a reduction in the cellular iron requirements. From a comparison to the genomic context of theT. pseudonana petFgene, theT. oceanicaortholog can be traced back to its chloroplast origin. The coding potential of theT. oceanicachloroplast genome is comparable to that ofT. pseudonanaandPhaeodactylum tricornutum, though a novel expressed ORF appears in the genomic region that has been subjected to rearrangements linked to thepetFgene transfer event.ConclusionsThe transfer of thepetFfrom the cp to the nuclear genome inT. oceanicarepresents a major difference between the two closely related species. The ability ofT. oceanicato tolerate iron limitation suggests that the transfer ofpetFfrom the chloroplast to the nuclear genome might have contributed to the ecological success of this species.
The vertebrate makorin ubiquitin ligase gene family has been shaped by large-scale duplication and retroposition from an ancestral gonad-specific, maternal-effect gene
Authors: Böhne Astrid , Darras Amandine , D'Cotta Helena , Baroiller Jean-Francois , Galiana-Arnoux Delphine , Volff Jean-Nicolas 
Published: January 2011

AbstractBackgroundMembers of the makorin(mkrn)gene family encode RING/C3H zinc finger proteins with U3 ubiquitin ligase activity. Although these proteins have been described in a variety of eukaryotes such as plants, fungi, invertebrates and vertebrates including human, almost nothing is known about their structural and functional evolution.ResultsVia partial sequencing of a testis cDNA library from the poeciliid fishXiphophorus maculatus, we have identified a new member of themakoringene family, that we calledmkrn4. In addition to the already describedmkrn1andmkrn2,mkrn4is the third example of a makorin gene present in both tetrapods and ray-finned fish. However, this gene was not detected in mouse and rat, suggesting its loss in the lineage leading to rodent murids.Mkrn2andmkrn4are located in large ancient duplicated regions in tetrapod and fish genomes, suggesting the possible involvement of ancestral vertebrate-specific genome duplication in the formation of these genes. Intriguingly, manymkrn1andmkrn2intronless retrocopies have been detected in mammals but not in other vertebrates, most of them corresponding to pseudogenes. The nature and number of zinc fingers were found to be conserved in Mkrn1 and Mkrn2 but much more variable in Mkrn4, with lineage-specific differences. RT-qPCR analysis demonstrated a highly gonad-biased expression pattern formakoringenes in medaka and zebrafish (ray-finned fishes) and amphibians, but a strong relaxation of this specificity in birds and mammals. All threemkrngenes were maternally expressed before zygotic genome activation in both medaka and zebrafish early embryos.ConclusionOur analysis demonstrates that themakoringene family has evolved through large-scale duplication and subsequent lineage-specific retroposition-mediated duplications in vertebrates. From the three major vertebratemkrngenes,mkrn4shows the highest evolutionary dynamics, with lineage-specific loss of zinc fingers and even complete gene elimination from certain groups of vertebrates. Comparative expression analysis strongly suggests that the ancestral E3 ubiquitin ligase function of the single copymkrngene before duplication in vertebrates was gonad-specific, with maternal expression in early embryos.
Global analysis of the eukaryotic pathways and networks regulated by Salmonella typhimurium in mouse intestinal infection in vivo
Authors: Liu Xingyin , Lu Rong , Xia Yinglin , Sun Jun 
Published: January 2011

AbstractBackgroundAcute enteritis caused bySalmonellais a public health concern.Salmonellainfection is also known to increase the risk of inflammatory bowel diseases and cancer. Therefore, it is important to understand howSalmonellaworks in targeting eukaryotic pathways in intestinal infection. However, the global physiological function ofSalmonellatyphimurium in intestinal mucosain vivois unclear. In this study, a whole genome approach combined with bioinformatics assays was used to investigate thein vivogenetic responses of the mouse colon toSalmonella. We focused on the intestinal responses in the early stage (8 hours) and late stage (4 days) afterSalmonellainfection.ResultsOf the 28,000 genes represented on the array, our analysis of mRNA expression in mouse colon mucosa showed that a total of 856 genes were expressed differentially at 8 hours post-infection. At 4 days post-infection, a total of 7558 genes were expressed differentially. 23 differentially expressed genes from the microarray data was further examined by real-time PCR. Ingenuity Pathways Analysis identified that the most significant pathway associated with the differentially expressed genes in 8 hours post-infection is oxidative phosphorylation, which targets the mitochondria. At the late stage of infection, a series of pathways associated with immune and inflammatory response, proliferation, and apoptosis were identified, whereas the oxidative phosphorylation was shut off. Histology analysis confirmed the biological role ofSalmonella, which induced a physiological state of inflammation and proliferation in the colon mucosa through the regulation of multiple signaling pathways. Most of the metabolism-related pathways were targeted by down-regulated genes, and a general repression process of metabolic pathways was observed. Network analysis supported IFN-γ and TNF-α function as mediators of the immune/inflammatory response for host defense against pathogen.ConclusionOur study provides novel genome-wide transcriptional profiling data on the mouse colon mucosa's response to theSalmonella typhimuriuminfection. Building the pathways and networks of interactions between these genes help us to understand the complex interplay in the mice colon duringSalmonellainfection, and further provide new insights into the molecular cascade, which is mobilized to combatSalmonella-associated colon infectionin vivo.