Discovering gene regulatory networks of multiple phenotypic groups using dynamic Bayesian networks

Dynamic Bayesian networks (DBNs) can be used for the discovery of gene regulatory networks from time series gene expression data. Here, we suggest a strategy for learning DBNs from gene expression data by employing a Bayesian approach that is scalable to large networks and is targeted at learning models with high predictive accuracy. Our framework can be used to learn DBNs for multiple groups of samples and highlight differences and similarities in their gene regulatory networks. We learn these DBN models based on different structural and parametric assumptions and select the optimal model based on the cross-validated predictive accuracy. We show in simulation studies that our approach is better equipped to prevent overfitting than techniques used in previous studies. We applied the proposed DBN-based classification approach to two time series transcriptomic datasets from the Gene Expression Omnibus database, each comprising data from distinct phenotypic groups of the same tissue type. In the first case, we used DBNs to characterize responders and non-responders to anti-cancer therapy. In the second case, we compared normal to tumor cells of colorectal tissue. The classification accuracy reached by the DBN-based classifier for both datasets was higher than reported previously. For the colorectal cancer dataset, our analysis suggested that GRNs for cancer and normal tissues have a lot of differences, which are most pronounced in the neighborhoods of oncogenes and known cancer tissue markers. The identified differences in gene networks of cancer and normal cells may be used for the discovery of targeted therapies.

The efficiency of SSR and ISSR markers for the assessment of genetic polymorphism of varieties and hybrids of garden chrysanthemum (Chrysanthemum × hortorum Bailey)

The genetic analysis of five varieties and seventeen hybrids of the collection of the Federal Research Centrethe Subtropical Scientific Centre of the Russian Academy of Sciences (FRC SSC RAS) of Sochi was carried out using DNAmarkers: SSR analysis and ISSR analysis. With the help of these markers, it was possible to identify the genetic differencesof the studied samples. At the same time, the analysis of phenotypic traits was carried out, which allowed us to dividethe studied plants into phenotypic groups. When processing genotypic and phenotypic groups, five related groups ofthe studied plants were identified. SSR-and ISSR-markers allow us to evaluate the genetic polymorphism of varieties andhybrids of Chrysanthemum × hortorum.

Uncovering Genomic Regions Regulating the Superoxide Dismutase, Flavonoids, Anthocyanins, Carotenoids, γ-Oryzanol and Antioxidant Activity in Rice Through Association Mapping

Consumption of antioxidants rich rice has impressive health benefits. Five antioxidant traits viz., superoxide dismutase, flavonoids, anthocyanins, γ-oryzanol and ABTS were mapped in a panel population using 136 SSR markers through association mapping. A panel population containing 120 germplasm lines by including genotypes from all the phenotypic groups of the six antioxidant traits from the original shortlisted 270 rice genotypes. Donor lines rich in multiple antioxidant compounds were identified from the population. The population was classified into 4 genetic groups and showed fair degree of correspondence with the antioxidants content. A total of 14 significant marker-trait associations for antioxidants were detected of which 3 QTLs namely qANC3, qPAC12-2 for anthocyanin content and qAC12 for ABTS activity were validated in the population. Eleven putative QTLs such as qTAC1.1 and qTAC5.1 for anthocyanin content; qSOD1.1, qSOD5.1 and qSOD10.1 for SOD; qTFC6.1, qTFC11.1 and qTFC12.1 for TFC; qOZ8.1 and qOZ11.1 for γ-oryzanol and qAC11.1 for ABTS were detected to be novel loci. Co-localization of the QTLs detected for OZ11.1, TFC11.1 and AC11.1 regulating γ-oryzanol, flavonoid and anthocyanin content, respectively while PAC12.2 for anthocyanin content remained closer to TFC12.1 for flavonoid content. These QTLs will be useful in the antioxidant improvement programs in rice.

The Urinary Microbiome in Postmenopausal Women with Recurrent Urinary Tract Infections

ABSTRACTRecurrent urinary tract infections (UTI) are highly prevalent in postmenopausal women, where vaginal estrogen and prophylactic antibiotics are used for treatment. The etiology of recurrent UTIs is not completely known, but the urinary microbiome is thought to be implicated. Thus, we aimed to compare the “steady state” urinary microbiome in three groups of menopausal women who were all using topically-applied vaginal estrogen: 1) women with recurrent UTIs on daily antibiotic prophylaxis; 2) women with recurrent UTIs not on antibiotic prophylaxis; and 3) age-matched controls without recurrent UTIs. Here we present a cross-sectional analysis of baseline data from 64 women enrolled in a longitudinal cohort study. Catheterized urine samples were collected > 4 weeks after last treatment for UTI. Samples were evaluated using expanded quantitative urine culture (EQUC) and 16S rRNA gene sequencing. With EQUC techniques, there were no significant differences in the median numbers of microbial species isolated among groups (p=0.96), even when considering Lactobacilli (p=0.72). However, there were trends towards different Lactobacillus species between groups. With sequencing the overwhelming majority of urinary samples contained Lactobacilli, with non-significant trends in relative abundance of Lactobacilli among groups. Using a Bayesian regression analysis for compositional data, we identified significant differences in anaerobic taxa that were associated with phenotypic groups. Most of these differences centered on Bacteroidales and the family Prevotellaceae, though differences were also noted in Actinobacteria and certain genera of Clostridiales. Associations between anaerobes within the urinary microbiome and recurrent UTI warrants further investigation.IMPORTANCEIn menopausal women with recurrent urinary tract infections (UTIs) compared to those without, the abundance of Lactobacillus within the urinary microbiome is not significantly different when vaginal estrogen is regularly used. In this population, Lactobacillaceae were identified in 97% of urine samples using culture-independent techniques. However, with expanded urine cultures, women with recurrent UTIs taking daily antibiotics had a disproportionately low amount of L. gasseri/L. acidophilus compared to the other phenotypic groups. These findings support the theory that certain Lactobacillus species may be more important than others in the pathophysiology of postmenopausal recurrent UTIs. Furthermore, when using culture-independent techniques to explore urinary microbiota across phenotypic groups, we identified differences in multiple anaerobic taxa. Taken together, these results suggest that altered ratios of anaerobes and certain Lactobacillus species within the urinary microbiome may be implicated in postmenopausal recurrent UTI.

Agromorphological Characterization Revealed Three Phenotypic Groups in a Region-Wide Germplasm of Fonio (Digitaria exilis (Kippist) Stapf) from West Africa

Fonio is an ancient orphan cereal, cultivated by resource-poor farmers in arid and semi-arid regions of West Africa, who conserved and used the cereal for nutrition and income generation. However, the extent and patterns of phenotypic variation within the fonio germplasm remain scarcely evaluated to inform breeding decisions. In this study, we used alpha lattice design to assess the phenotypic variability of 180 fonio accessions using 20 agro morphological descriptors, including both qualitative and quantitative traits at Bengou research station in 2018 and 2019. Descriptive statistics, combined analysis and multivariate analyses, including principal components analysis (PCA), hierarchical clustering, and multiple factor analysis (MFA) were performed. As results, we found significant differences among fonio accessions and among agro ecological zones of provenance for most of the quantitative traits. Furthermore, highly significant positive correlations were found between grain yield and other yield-related attributes such as harvest index and thousand seeds weight, whereas significant negative correlations were found between grain yield and flowering and maturity times. Clusters analysis revealed three phenotypic groups. Group 1 was characterized by early maturing fonio accessions with higher grain yield. Groups 2 and 3 were characterized by late maturing accessions with intermediate to moderate grain yield. The accessions from Group 1 are candidate for yield improvement and development of fonio lines with enhanced lodging resistance. Accessions from Group 2 and 3 can be improved for yield through marker-assisted selection of best thousand seed weight. This study highlights how traits are correlated within the major phenotypic groups of fonio in West Africa, and we discussed how these groups could be further exploited for improving traits of economic importance. Furthermore, this study exhibited agro morphological descriptors that discriminate fonio accessions and provide useful information for parental selection with economically important agronomic traits.

Identification of Candidate Genes Involved in Fruit Ripening and Crispness Retention Through Transcriptome Analyses of a ‘Honeycrisp’ Population

Crispness retention is a postharvest trait that fruit of the ’Honeycrisp’ apple and some of its progeny possess. To investigate the molecular mechanisms of crispness retention, progeny individuals derived from a ’Honeycrisp’ × MN1764 population with fruit that either retain crispness (named “Retain”), lose crispness (named “Lose”), or that are not crisp at harvest (named “Non-crisp”) were selected for transcriptomic comparisons. Differentially expressed genes (DEGs) were identified using RNA-Seq, and the expression levels of the DEGs were validated using nCounter®. Functional annotation of the DEGs revealed distinct ripening behaviors between fruit of the “Retain” and “Non-crisp” individuals, characterized by opposing expression patterns of auxin- and ethylene-related genes. However, both types of genes were highly expressed in the fruit of “Lose” individuals and ’Honeycrisp’, which led to the potential involvements of genes encoding auxin-conjugating enzyme (GH3), ubiquitin ligase (ETO), and jasmonate O-methyltransferase (JMT) in regulating fruit ripening. Cell wall-related genes also differentiated the phenotypic groups; greater numbers of cell wall synthesis genes were highly expressed in fruit of the “Retain” individuals and ’Honeycrisp’ when compared with “Non-crisp” individuals and MN1764. On the other hand, the phenotypic differences between fruit of the “Retain” and “Lose” individuals could be attributed to the functioning of fewer cell wall-modifying genes. A cell wall-modifying gene, MdXTH, was consistently identified as differentially expressed in those fruit over two years in this study, so is a major candidate for crispness retention.

A Practical Guide to the New Feline Cardiomyopathy Consensus Statement

In a welcome move, the American College of Veterinary Internal Medicine (ACVIM) has just published a consensus statement providing guidance on the diagnosis, management, and treatment of the cat with cardiomyopathy. Even more encouraging is that nursing guidelines have also been included in this statement. The paper has been released as ‘open access’, so anyone can access these guidelines free of charge online. The consensus statement is important because it provides an updated classification of feline cardiomyopathies, changing emphasis to different phenotypic groups, and adds a staging system, along similar lines as the ACVIM myxomatous mitral valve disease consensus statement first published in 2009 and then updated in 2019. This article provides a summary of the key points made in the consensus statement.

The Nature of Espeletia Species

Species are often regarded as basic units of study in biology, following the presumption that they are real and discrete natural entities. But several biologists wonder if species are arbitrary divisions that do not correspond to discrete natural groups of organisms. Two issues must be addressed to solve this controversy, but few studies seem to do so. The first is whether organisms form sympatric and synchronic groups that are distinct in terms of phenotypes and genome-wide allele frequencies, often called “good species.” Alternatives to “good species” include “cryptic species,” syngameons and, more generally, cases in which phenotypes and genome-wide allele frequencies reflect contrasting evolutionary histories. The second issue is the degree to which species taxa (i.e., taxonomic classification at the species level) reflect natural groups of organisms or constitute arbitrary divisions of biological diversity. Here, we empirically addressed both issues by studying plants of the Andean genus Espeletia (Asteraceae). We collected a geographically dense sample of 538 specimens from the paramo de Sumapaz, in the Cordillera Oriental of Colombia. Additionally, we examined 165 herbarium specimens previously collected by other researchers in this region, or from taxa known to occur there. We tested for the existence of phenotypic groups using normal mixture models and data on 13 quantitative characters. Among 307 specimens with all 13 measurements, we found six distinct phenotypic groups in sympatry. We also tested for the existence of groups defined by genome-wide allele frequencies, using ancestry models and data on 2,098 single nucleotide polymorphisms. Among 77 specimens with complete genomic data, we found three groups in sympatry, with high levels of admixture. Concordance between groups defined by phenotype and genome-wide allele frequencies was low, suggesting that phenotypes and genome-wide allele frequencies reflect contrasting evolutionary histories. Moreover, the high levels of admixture suggest that Espeletia plants form a syngameon in the paramo de Sumapaz. To determine the extent to which species taxa corresponded to phenotypic and genomic groups, we used data on 12 phenotypic characters to assign 307 specimens to species taxa, according to descriptions of species taxa in the most recent monograph of Espeletia. This sample included 27 specimens cited in the monograph. Remarkably, only one out of 307 specimens in our sample fell inside any of the phenotypic ranges reported in the monograph for the species taxa known to occur in the paramo de Sumapaz. These results show that species taxa in Espeletia are delineations of largely empty phenotypic space that miss biological diversity.

Probability distribution of copy number alterations along the genome: an algorithm to distinguish different tumour profiles

Copy number alterations (CNAs) comprise deletions or amplifications of fragments of genomic material that are particularly common in cancer and play a major contribution in its development and progression. High resolution microarray-based genome-wide technologies have been widely used to detect CNAs, generating complex datasets that require further steps to allow for the determination of meaningful results. In this work, we propose a methodology to determine common regions of CNAs from these datasets, that in turn are used to infer the probability distribution of disease profiles in the population. This methodology was validated using simulated data and assessed using real data from Head and Neck Squamous Cell Carcinoma and Lung Adenocarcinoma, from the TCGA platform. Probability distribution profiles were produced allowing for the distinction between different phenotypic groups established within that cohort. This method may be used to distinguish between groups in the diseased population, within well-established degrees of confidence. The application of such methods may be of greater value in the clinical context both as a diagnostic or prognostic tool and, even as a useful way for helping to establish the most adequate treatment and care plans.