Clustering Scatter Plots Using Data Depth Measures.

Clustering is rapidly becoming a powerful data mining technique, and has been broadly applied to many domains such as bioinformatics and text mining. However, the existing methods can only deal with a data matrix of scalars. In this paper, we introduce a hierarchical clustering procedure that can handle a data matrix of scatter plots. To more accurately reflect the nature of data, we introduce a dissimilarity statistic based on "data depth" to measure the discrepancy between two bivariate distributions without oversimplifying the nature of the underlying pattern. We then combine hypothesis testing with hierarchical clustering to simultaneously cluster the rows and columns of the data matrix of scatter plots. We also propose novel painting metrics and construct heat maps to allow visualization of the clusters. We demonstrate the utility and power of our new clustering method through simulation studies and application to a microbe-host-interaction study

Wilks’ Factorization of the Complex Matrix Variate Dirichlet Distributions

In this paper, it has been shown that the complex matrix variate Dirichlet type I density factors into the complex matrix variate beta type I densities. Similar result has also been derived for the complex matrix variate Dirichlet type II density. Also, by using certain matrix transformations, the complex matrix variate Dirichlet distributions have been generated from the complex matrix beta distributions. Further, several results on the product of complex Wishart and complex beta matrices with a set of complex Dirichlet type I matrices have been derived.In this paper, it has been shown that the complex matrix variate Dirichlet type I density factors into the complex matrix variate beta type I densities. Similar result has also been derived for the complex matrix variate Dirichlet type II density. Also, by using certain matrix transformations, the complex matrix variate Dirichlet distributions have been generated from the complex matrix beta distributions. Further, several results on the product of complex Wishart and complex beta matrices with a set of complex Dirichlet type I matrices have been derived

Comparing genomic expression patterns across plant species reveals highly diverged transcriptional dynamics in response to salt stress

BackgroundRice and barley are both members of Poaceae (grass family) but have a marked difference in salt tolerance. The molecular mechanism underlying this difference was previously unexplored. This study employs a comparative genomics approach to identify analogous and contrasting gene expression patterns between rice and barley.ResultsA hierarchical clustering approach identified several interesting expression trajectories among rice and barley genotypes. There were no major conserved expression patterns between the two species in response to salt stress. A wheat salt-stress dataset was queried for comparison with rice and barley. Roughly one-third of the salt-stress responses of barley were conserved with wheat while overlap between wheat and rice was minimal. These results demonstrate that, at transcriptome level, rice is strikingly different compared to the more closely related barley and wheat. This apparent lack of analogous transcriptional programs in response to salt stress is further highlighted through close examination of genes associated with root growth and development.ConclusionThe analysis provides support for the hypothesis that conservation of transcriptional signatures in response to environmental cues depends on the genetic similarity among the genotypes within a species, and on the phylogenetic distance between the species

Array-based genotyping and expression analysis of barley cv. Maythorpe and Golden Promise

BACKGROUND: Golden Promise is a salt-tolerant spring barley closely related to Maythorpe. Salt tolerance in Golden Promise has been attributed to a single mutation at the Ari-e locus (on 5H) resulting from irradiation of Maythorpe. Golden Promise accumulates lower shoot Na(+ )compared to Maythorpe when growing under saline conditions. This study focused on elucidating the genetic basis and mechanisms involved in this difference. RESULTS: The level of polymorphism between the two genotypes was explored using the Barley1 GeneChip for single feature polymorphisms (SFPs) and an oligonucleotide pool assay for single nucleotide polymorphisms (SNPs). Polymorphism analyses revealed three haplotype blocks spanning 6.4 cM on chromosome 1H, 23.7 cM on chromosome 4H and 3.0 cM on 5H. The Barley1 GeneChip was used to examine transcript abundance in different tissues and stages during development. Several genes within the polymorphic haplotype blocks were differentially regulated. Additionally, a more global difference in the jasmonic acid pathway regulation was detected between the two genotypes. CONCLUSION: The results confirm that Golden Promise and Maythorpe are genetically very closely related but establish that they are not isogenic, as previously reported, due to three polymorphic haplotype blocks. Transcriptome analysis indicates that the response of the two genotypes to salinity stress is quite different. Additionally, the response to salinity stress in the roots and shoot tissue is strikingly different

Learning from real world data about combinatorial treatment selection for COVID-19

COVID-19 is an unprecedented global pandemic with a serious negative impact on virtually every part of the world. Although much progress has been made in preventing and treating the disease, much remains to be learned about how best to treat the disease while considering patient and disease characteristics. This paper reports a case study of combinatorial treatment selection for COVID-19 based on real-world data from a large hospital in Southern China. In this observational study, 417 confirmed COVID-19 patients were treated with various combinations of drugs and followed for four weeks after discharge (or until death). Treatment failure is defined as death during hospitalization or recurrence of COVID-19 within four weeks of discharge. Using a virtual multiple matching method to adjust for confounding, we estimate and compare the failure rates of different combinatorial treatments, both in the whole study population and in subpopulations defined by baseline characteristics. Our analysis reveals that treatment effects are substantial and heterogeneous, and that the optimal combinatorial treatment may depend on baseline age, systolic blood pressure, and c-reactive protein level. Using these three variables to stratify the study population leads to a stratified treatment strategy that involves several different combinations of drugs (for patients in different strata). Our findings are exploratory and require further validation

Detection and validation of single feature polymorphisms in cowpea (Vigna unguiculata L. Walp) using a soybean genome array

<p>Abstract</p> <p>Background</p> <p>Cowpea (<it>Vigna unguiculata </it>L. Walp) is an important food and fodder legume of the semiarid tropics and subtropics worldwide, especially in sub-Saharan Africa. High density genetic linkage maps are needed for marker assisted breeding but are not available for cowpea. A single feature polymorphism (SFP) is a microarray-based marker which can be used for high throughput genotyping and high density mapping.</p> <p>Results</p> <p>Here we report detection and validation of SFPs in cowpea using a readily available soybean (<it>Glycine max) </it>genome array. Robustified projection pursuit (RPP) was used for statistical analysis using RNA as a surrogate for DNA. Using a 15% outlying score cut-off, 1058 potential SFPs were enumerated between two parents of a recombinant inbred line (RIL) population segregating for several important traits including drought tolerance, <it>Fusarium </it>and brown blotch resistance, grain size and photoperiod sensitivity. Sequencing of 25 putative polymorphism-containing amplicons yielded a SFP probe set validation rate of 68%.</p> <p>Conclusion</p> <p>We conclude that the Affymetrix soybean genome array is a satisfactory platform for identification of some 1000's of SFPs for cowpea. This study provides an example of extension of genomic resources from a well supported species to an orphan crop. Presumably, other legume systems are similarly tractable to SFP marker development using existing legume array resources.</p

Detection and validation of single feature polymorphisms using RNA expression data from a rice genome array

<p>Abstract</p> <p>Background</p> <p>A large number of genetic variations have been identified in rice. Such variations must in many cases control phenotypic differences in abiotic stress tolerance and other traits. A single feature polymorphism (SFP) is an oligonucleotide array-based polymorphism which can be used for identification of SNPs or insertion/deletions (INDELs) for high throughput genotyping and high density mapping. Here we applied SFP markers to a lingering question about the source of salt tolerance in a particular rice recombinant inbred line (RIL) derived from a salt tolerant and salt sensitive parent.</p> <p>Results</p> <p>Expression data obtained by hybridizing RNA to an oligonucleotide array were analyzed using a statistical method called robustified projection pursuit (RPP). By applying the RPP method, a total of 1208 SFP probes were detected between two presumed parental genotypes (Pokkali and IR29) of a RIL population segregating for salt tolerance. We focused on the <it>Saltol </it>region, a major salt tolerance QTL. Analysis of FL478, a salt tolerant RIL, revealed a small (< 1 Mb) region carrying alleles from the presumed salt tolerant parent, flanked by alleles matching the salt sensitive parent IR29. Sequencing of putative SFP-containing amplicons from this region and other positions in the genome yielded a validation rate more than 95%.</p> <p>Conclusion</p> <p>Recombinant inbred line FL478 contains a small (< 1 Mb) segment from the salt tolerant parent in the <it>Saltol </it>region. The Affymetrix rice genome array provides a satisfactory platform for high resolution mapping in rice using RNA hybridization and the RPP method of SFP analysis.</p

Mapping translocation breakpoints using a wheat microarray

We report mapping of translocation breakpoints using a microarray. We used complex RNA to compare normal hexaploid wheat (17 000 Mb genome) to a ditelosomic stock missing the short arm of chromosome 1B (1BS) and wheat-rye translocations that replace portions of 1BS with rye 1RS. Transcripts detected by a probe set can come from all three Triticeae genomes in ABD hexaploid wheat, and sequences of homoeologous genes on 1AS, 1BS and 1DS often differ from each other. Absence or replacement of 1BS therefore must sometimes result in patterns within a probe set that deviate from hexaploid wheat. We termed these ‘high variance probe sets’ (HVPs) and examined the extent to which HVPs associated with 1BS aneuploidy are related to rice genes on syntenic rice chromosome 5 short arm (5S). We observed an enrichment of such probe sets to 15–20% of all HVPs, while 1BS represents ∼2% of the total genome. In total 257 HVPs constitute wheat 1BS markers. Two wheat-rye translocations subdivided 1BS HVPs into three groups, allocating translocation breakpoints to narrow intervals defined by rice 5S coordinates. This approach could be extended to the entire wheat genome or any organism with suitable aneuploid or translocation stocks

Single feature polymorphisms (SFPs) for drought tolerance in pigeonpea (Cajanus spp.)

Single feature polymorphisms (SFPs) are microarray-based molecular markers that are detected by hybridization of DNA or cRNA to oligonucleotide probes. With an objective to identify the potential polymorphic markers for drought tolerance in pigeonpea [Cajanus cajan (L.) Millspaugh], an important legume crop for the semi-arid tropics but deficient in genomic resources, Affymetrix Genome Arrays of soybean (Glycine max), a closely related species of pigeonpea were used on cRNA of six parental genotypes of three mapping populations of pigeonpea segregating for agronomic traits like drought tolerance and pod borer (Helicoverpa armigiera) resistance. By using robustified projection pursuit method on 15 pair-wise comparisons for the six parental genotypes, 5,692 SFPs were identified. Number of SFPs varied from 780 (ICPL 8755 × ICPL 227) to 854 (ICPL 151 × ICPL 87) per parental combination of the mapping populations. Randomly selected 179 SFPs were used for validation by Sanger sequencing and good quality sequence data were obtained for 99 genes of which 75 genes showed sequence polymorphisms. While associating the sequence polymorphisms with SFPs detected, true positives were observed for 52.6% SFPs detected. In terms of parental combinations of the mapping populations, occurrence of true positives was 34.48% for ICPL 151 × ICPL 87, 41.86% for ICPL 8755 × ICPL 227, and 81.58% for ICP 28 × ICPW 94. In addition, a set of 139 candidate genes that may be associated with drought tolerance has been identified based on gene ontology analysis of the homologous pigeonpea genes to the soybean genes that detected SFPs between the parents of the mapping populations segregating for drought tolerance