Detecting differential expression in microarray data: comparison of optimal procedures

BACKGROUND: Many procedures for finding differentially expressed genes in microarray data are based on classical or modified t-statistics. Due to multiple testing considerations, the false discovery rate (FDR) is the key tool for assessing the significance of these test statistics. Two recent papers have generalized two aspects: Storey et al. (2005) have introduced a likelihood ratio test statistic for two-sample situations that has desirable theoretical properties (optimal discovery procedure, ODP), but uses standard FDR assessment; Ploner et al. (2006) have introduced a multivariate local FDR that allows incorporation of standard error information, but uses the standard t-statistic (fdr2d). The relationship and relative performance of these methods in two-sample comparisons is currently unknown. METHODS: Using simulated and real datasets, we compare the ODP and fdr2d procedures. We also introduce a new procedure called S2d that combines the ODP test statistic with the extended FDR assessment of fdr2d. RESULTS: For both simulated and real datasets, fdr2d performs better than ODP. As expected, both methods perform better than a standard t-statistic with standard local FDR. The new procedure S2d performs as well as fdr2d on simulated data, but performs better on the real data sets. CONCLUSION: The ODP can be improved by including the standard error information as in fdr2d. This means that the optimality enjoyed in theory by ODP does not hold for the estimated version that has to be used in practice. The new procedure S2d has a slight advantage over fdr2d, which has to be balanced against a significantly higher computational effort and a less intuititive test statistic

Integrable boundary interaction in 3D target space: the "pillow-brane" model

We propose a model of boundary interaction, with three-dimensional target space, and the boundary values of the field {\vec X}\in R^3 constrained to lay on a two-dimensional surface of the "pillow" shape. We argue that the model is integrable, and suggest that its exact solution is described in terms of certain linear ordinary differential equation.Comment: 28 pages, 4 figure

Inactivation of the extrinsic subunit of photosystem II, PsbU, in Synechococcus PCC 7942 results in elevated resistance to oxidative stress

AbstractPsbU is a subunit of the extrinsic complex attached to the core of photosystem II. A PsbU-mutant of Synechococcus PCC 7942 was isolated based on its elevated resistance to externally applied oxidative stress. PsbU-mutant exhibits fast rates of degradation of the photosystem II core protein, D1, under sub-saturating as well as high-light conditions. While forward electron transfer is not affected, back electron flow is severely impaired in the mutant. We suggest that impairment of psbU results in production of reactive-oxygen-species, which trigger antioxidative mechanisms even under standard growth conditions. Accordingly, when challenged with external oxidative stress, these cells are more resistant than wild type cells

Pinniped Karyotype Evolution Substantiated by Comparative Chromosome Painting of 10 Pinniped Species (Pinnipedia, Carnivora)

Numerous Carnivora karyotype evolution investigations have been performed by classical and molecular cytogenetics and were supplemented by reconstructions of the Ancestral Carnivora Karyotype (ACK). However, the group of Pinnipedia was not studied in detail. Here we reconstruct pinniped karyotype evolution and refine ACK using published and our new painting data for 10 pinniped species. The combination of human (HSA) and domestic dog (CFA) whole-chromosome painting probes was used for the construction of the comparative chromosome maps for species from all three pinniped families: Odobenidae– Odobenus rosmarus Linnaeus, 1758, Phocidae – Phoca vitulina Linnaeus, 1758, Pusa sibirica Gmelin, 1788, Erignathus barbatus Erxleben, 1777, Phoca largha Pallas, 1811, Phoca hispida Schreber, 1775 and Otariidae – Eumetopias jubatus Schreber, 1775, Callorhinus ursinus Linnaeus, 1758, Phocarctos hookeri Gray, 1844, Arctocephalus forsteri Lesson, 1828. HSA and CFA autosome painting probes have delineated 32 and 68 conservative autosome segments in the studied genomes. The comparative painting in Pinnipedia supports monophyletic origin of pinnipeds, shows that pinniped karyotype evolution was characterized by slow rate of genome rearrangements (less then one rearrangement per 10 million years), provides strong support for refined structure of ACK with 2n = 38 and specifies plausible order of dog chromosome synthenic segments on ancestral Carnivora chromosomes. The heterochromatin, telomere and ribosomal DNA distribution was studied in all 10 species

Transcription of a protein-coding gene on B chromosomes of the Siberian roe deer (Capreolus pygargus)

BACKGROUND: Most eukaryotic species represent stable karyotypes with a particular diploid number. B chromosomes are additional to standard karyotypes and may vary in size, number and morphology even between cells of the same individual. For many years it was generally believed that B chromosomes found in some plant, animal and fungi species lacked active genes. Recently, molecular cytogenetic studies showed the presence of additional copies of protein-coding genes on B chromosomes. However, the transcriptional activity of these genes remained elusive. We studied karyotypes of the Siberian roe deer (Capreolus pygargus) that possess up to 14 B chromosomes to investigate the presence and expression of genes on supernumerary chromosomes. RESULTS: Here, we describe a 2 Mbp region homologous to cattle chromosome 3 and containing TNNI3K (partial), FPGT, LRRIQ3 and a large gene-sparse segment on B chromosomes of the Siberian roe deer. The presence of the copy of the autosomal region was demonstrated by B-specific cDNA analysis, PCR assisted mapping, cattle bacterial artificial chromosome (BAC) clone localization and quantitative polymerase chain reaction (qPCR). By comparative analysis of B-specific and non-B chromosomal sequences we discovered some B chromosome-specific mutations in protein-coding genes, which further enabled the detection of a FPGT-TNNI3K transcript expressed from duplicated genes located on B chromosomes in roe deer fibroblasts. CONCLUSIONS: Discovery of a large autosomal segment in all B chromosomes of the Siberian roe deer further corroborates the view of an autosomal origin for these elements. Detection of a B-derived transcript in fibroblasts implies that the protein coding sequences located on Bs are not fully inactivated. The origin, evolution and effect on host of B chromosomal genes seem to be similar to autosomal segmental duplications, which reinforces the view that supernumerary chromosomal elements might play an important role in genome evolution

Karyotype Evolution in 10 Pinniped Species: Variability of Heterochromatin versus High Conservatism of Euchromatin as Revealed by Comparative Molecular Cytogenetics

Pinnipedia karyotype evolution was studied here using human, domestic dog, and stone marten whole-chromosome painting probes to obtain comparative chromosome maps among species of Odobenidae (Odobenus rosmarus), Phocidae (Phoca vitulina, Phoca largha, Phoca hispida, Pusa sibirica, Erignathus barbatus), and Otariidae (Eumetopias jubatus, Callorhinus ursinus, Phocarctos hookeri, and Arctocephalus forsteri). Structural and functional chromosomal features were assessed with telomere repeat and ribosomal-DNA probes and by CBG (C-bands revealed by barium hydroxide treatment followed by Giemsa staining) and CDAG (Chromomycin A3-DAPI after G-banding) methods. We demonstrated diversity of heterochromatin among pinniped karyotypes in terms of localization, size, and nucleotide composition. For the first time, an intrachromosomal rearrangement common for Otariidae and Odobenidae was revealed. We postulate that the order of evolutionarily conserved segments in the analyzed pinnipeds is the same as the order proposed for the ancestral Carnivora karyotype (2n = 38). The evolution of conserved genomes of pinnipeds has been accompanied by few fusion events (less than one rearrangement per 10 million years) and by novel intrachromosomal changes including the emergence of new centromeres and pericentric inversion/centromere repositioning. The observed interspecific diversity of pinniped karyotypes driven by constitutive heterochromatin variation likely has played an important role in karyotype evolution of pinnipeds, thereby contributing to the differences of pinnipeds’ chromosome sets

X Chromosome Evolution in Cetartiodactyla

The mammalian X chromosome is characterized by high level of conservation. On the contrary the Cetartiodactyl X chromosome displays variation in morphology and G-banding pattern. It is hypothesized that X chromosome has undergone multiple rearrangements during Cetartiodactyla speciation. To investigate the evolution of this sex chromosome we have selected 26 BAC clones from cattle CHORI-240 library evenly distributed along the cattle X chromosome. High-resolution maps were obtained by fluorescence in situ hybridisation in a representative range of cetartiodactyl species from different families: pig (Suidae), gray whale (Eschrichtiidae), pilot whale (Delphinidae), hippopotamus (Hippopotamidae), Java mouse deer (Tragulidae), pronghorn (Antilocapridae), Siberian musk deer (Moschidae), giraffe (Giraffidae). To trace the X chromosome evolution during fast radiation in speciose families, we mapped more than one species in Cervidae (moose, Siberian roe deer, fallow deer and Pere David’s deer) and Bovidae (musk ox, goat, sheep, sable antelope, nilgau, gaur, saola, and cattle). We have identified three major conserved synteny blocks and based on this data reconstructed the structure of putative ancestral cetartiodactyl X chromosome. We demonstrate that intrachromosomal rearrangements such as inversions and centromere reposition are main drivers of cetartiodactyl’s chromosome X evolution

Draft de novo Genome Assembly of the Elusive Jaguarundi, Puma yagouaroundi

The Puma lineage within the family Felidae consists of 3 species that last shared a common ancestor around 4.9 million years ago. Whole-genome sequences of 2 species from the lineage were previously reported: the cheetah (Acinonyx jubatus) and the mountain lion (Puma concolor). The present report describes a whole-genome assembly of the remaining species, the jaguarundi (Puma yagouaroundi). We sequenced the genome of a male jaguarundi with 10X Genomics linked reads and assembled the whole-genome sequence. The assembled genome contains a series of scaffolds that reach the length of chromosome arms and is similar in scaffold contiguity to the genome assemblies of cheetah and puma, with a contig N50 = 100.2 kbp and a scaffold N50 = 49.27 Mbp. We assessed the assembled sequence of the jaguarundi genome using BUSCO, aligned reads of the sequenced individual and another published female jaguarundi to the assembled genome, annotated protein-coding genes, repeats, genomic variants and their effects with respect to the protein-coding genes, and analyzed differences of the 2 jaguarundis from the reference mitochondrial genome. The jaguarundi genome assembly and its annotation were compared in quality, variants, and features to the previously reported genome assemblies of puma and cheetah. Computational analyzes used in the study were implemented in transparent and reproducible way to allow their further reuse and modification. </p

X Chromosome Evolution in Cetartiodactyla

The phenomenon of a remarkable conservation of the X chromosome in eutherian mammals has been first described by Susumu Ohno in 1964. A notable exception is the cetartiodactyl X chromosome, which varies widely in morphology and G-banding pattern between species. It is hypothesized that this sex chromosome has undergone multiple rearrangements that changed the centromere position and the order of syntenic segments over the last 80 million years of Cetartiodactyla speciation. To investigate its evolution we have selected 26 evolutionarily conserved bacterial artificial chromosome (BAC) clones from the cattle CHORI-240 library evenly distributed along the cattle X chromosome. High-resolution BAC maps of the X chromosome on a representative range of cetartiodactyl species from different branches: pig (Suidae), alpaca (Camelidae), gray whale (Cetacea), hippopotamus (Hippopotamidae), Java mouse-deer (Tragulidae), pronghorn (Antilocapridae), Siberian musk deer (Moschidae), and giraffe (Giraffidae) were obtained by fluorescent in situ hybridization. To trace the X chromosome evolution during fast radiation in specious families, we performed mapping in several cervids (moose, Siberian roe deer, fallow deer, and Pere David’s deer) and bovid (muskox, goat, sheep, sable antelope, and cattle) species. We have identified three major conserved synteny blocks and rearrangements in different cetartiodactyl lineages and found that the recently described phenomenon of the evolutionary new centromere emergence has taken place in the X chromosome evolution of Cetartiodactyla at least five times. We propose the structure of the putative ancestral cetartiodactyl X chromosome by reconstructing the order of syntenic segments and centromere position for key groups