Biology subjects

Borgan, O.

Publications and source records attributed to Borgan, O..

6 recordsLinked to original sources

bioRxiv2020

Tailored Graphical Lasso for Data Integration in Gene Network Reconstruction

BackgroundIdentifying gene interactions is a topic of great importance in genomics, and approaches based on network models provide a powerful tool for studying these. Assuming a Gaussian graphical model, a gene association network may be estimated from multiomic data based on the non-zero entries of the inverse covariance matrix. Inferring such biological networks is challenging because of the high dimensionality of the problem, making traditional estimators unsuitable. The graphical lasso is constructed for the estimation of sparse inverse covariance matrices in Gaussian graphical models in such situations, using L1-penalization on the matrix entries. An extension of the graphical lasso is the weighted graphical lasso, in which prior biological information from other (data) sources is integrated into the model through the weights. There are however issues with this approach, as it naively forces the prior information into the network estimation, even if it is misleading or does not agree with the data at hand. Further, if an associated network based on other data is used as the prior, weighted graphical lasso often fails to utilize the information effectively. ResultsWe propose a novel graphical lasso approach, the tailored graphical lasso, that aims to handle prior information of unknown accuracy more effectively. We provide an R package implementing the method, tailoredGlasso. Applying the method to both simulated and real multiomic data sets, we find that it outperforms the unweighted and weighted graphical lasso in terms of all performance measures we consider. In fact, the graphical lasso and weighted graphical lasso can be considered special cases of the tailored graphical lasso, and a parameter determined by the data measures the usefulness of the prior information. With our method, mRNA data are demonstrated to provide highly useful prior information for protein-protein interaction networks. ConclusionsThe method we introduce utilizes useful prior information more effectively without involving any risk of loss of accuracy should the prior information be misleading.

bioinformatics↗

bioRxiv2019

Metagenomic shotgun analyses reveal complex patterns of intra- and interspecific variation in the intestinal microbiomes of codfishes

The relative importance of host-specific selection or environmental factors in determining the composition of the intestinal microbiome in wild vertebrates remains poorly understood. Here, we use metagenomic shotgun sequencing of individual specimens to compare the intra- and interspecific variation of intestinal microbiome communities in two ecotypes (NEAC and NCC) of Atlantic cod (Gadus morhua) - that have distinct behavior and habitats- and three Gadidae species that occupy a range of ecological niches. Interestingly, we find significantly diverged microbiomes amongst the two Atlantic cod ecotypes. Interspecific patterns of variation are more variable, with significantly diverged communities for most species comparisons, apart from the comparison between coastal cod (NCC) and Norway pout (Trisopterus esmarkii), whose community compositions are not significantly diverged. The absence of consistent species-specific microbiomes suggests that external environmental factors, such as temperature, diet or a combination there-off comprise major drivers of the intestinal community composition of codfishes. ImportanceThe composition of the intestinal microbial community associated with teleost fish is influenced by a diversity of factors, ranging from internal factors (such as host-specific selection) to external factors (such as niche occupation). These factors are often difficult to separate, as differences in niche occupation (e.g. diet, temperature or salinity) may correlate with distinct evolutionary trajectories. Here, we investigate four gadoid species with contrasting levels of evolutionary separation and niche occupation. Using metagenomic shotgun sequencing, we observe distinct microbiomes amongst two Atlantic cod (Gadus morhua) ecotypes (NEAC and NCC) with distinct behavior and habitats. In contrast, interspecific patterns of variation are more variable. For instance, we do not observe interspecific differentiation between the microbiomes of coastal cod (NCC) and Norway pout (Trisopterus esmarkii) whose lineages have evolutionary separated over 20 million years ago. The observed pattern of microbiome variation in these gadoid species is therefore most parsimoniously explained by differences in niche occupation.

microbiology↗

bioRxiv2019

Copy number motifs expose genome instability type and predict driver events and disease outcome in breast cancer

Tumor evolution is dependent on and constrained by the genotypes emerging from genome instability. We hypothesized that non-site-specific copy number motifs would correlate with underlying replication defects and also with tumor and patient fate. Six feature detectors were defined to characterize and score the local spatial behaviour of a copy number profile. By accumulating scores across genomic regions, a low-dimensional representation of the tumor genome was obtained. The proposed Copy Aberration Regional Mapping Analysis (CARMA) algorithm was applied to 2384 breast tumors from three breast cancer cohorts, revealing distinct copy number motifs in established molecular subtypes. A prognostic index combining the features predicted breast cancer specific survival better than both the genomic instability index (GII) and all commonly used clinical stratifications. CARMA offers effective comparison of tumor subgroups and extracts biologically and clinically relevant features from allele-specific copy number profiles.

bioinformatics↗

bioRxiv2019

Switching on the light: using metagenomic shotgun sequencing to characterize the intestinal microbiome of Atlantic cod

The biological roles of the intestinal microbiome and how it is impacted by environmental factors are yet to be determined in wild marine fish species. Atlantic cod (Gadus morhua) is an ecologically important species with a wide-spread distribution in the North Atlantic Ocean. 16S rRNA-based amplicon analyses found no geographical differentiation between the intestinal microbiome of Atlantic cod from different locations. Nevertheless, it is unclear if this lack of differentiation results from an insufficient resolution of this method to resolve fine-scaled biological complexity. Here, we take advantage of the increased resolution provided by metagenomic shotgun sequencing to investigate the intestinal microbiome of 19 adult Atlantic cod individuals from two coastal populations in Norway - located 470 km apart. Our results show that the intestinal microbiome is dominated by the Vibrionales order, consisting of varying abundances of Photobacterium, Aliivibrio and Vibrio species. Moreover, resolving the species community to unprecedented resolution, we identify two abundant species, P. iliopiscarium and P. kishitanii, which comprise over 50% of the classified reads. Interestingly, genomic data shows that the intestinal P. kishitanii strains have functionally intact lux genes, and its high abundance suggests that fish intestines form an important part of its ecological niche. These observations support a hypothesis that bioluminescence plays an ecological role in the marine food web. Despite our improved taxonomical resolution, we identify no geographical differences in bacterial community structure, indicating that the intestinal microbiome of these coastal cod is colonized by a limited number of closely related bacterial species with a broad geographical distribution that are well suited to thrive in this host-associated environment.

microbiology↗

bioRxiv2017

Study mortality with hazard rates, not probabilities

O_LIMortality is a key process in ecology and evolution, and much effort is spent on statistical and theoretical modelling of this process. Mortality hazard rates describe individuals instantaneous ability to survive at different times, whereas survival probabilities are defined for time-intervals of a given length. In this commentary, we argue that it is often more meaningful to model and interpret interval-specific time-averaged mortality hazard rates than survival probabilities, also when using discrete-time models.\nC_LIO_LIWe discuss three topics where the concept of hazard rates is essential for sound biological inference, but nevertheless often not used: (i) modelling of covariate effects on survival probabilities or mortality hazard rates, (ii) modelling of multiple sources of mortality and competing risks, and (iii) elasticity analyses of population growth rate to demographic parameters. To facilitate estimation of cause-specific mortality hazard rates, we provide amendments to R package marked.\nC_LIO_LIBy focusing on modelling mortality hazard rates, one avoids several inherent problems of comparing survival or mortality probabilities. In particular, interpretations about relative differences between mortality hazard rates (measurements on a ratio scale), or effects of relative changes in mortality hazard rates on population growth (elasticities), are more meaningful than similar interpretations involving survival (or mortality) probabilities or odds (measurements on an absolute scale).\nC_LIO_LIThe concept of hazard rates is essential for understanding ecological and evolutionary processes and we give an intuitive explanation for this, using several examples. We provide some practical guidelines and suggestions for further methods developments.\nC_LI

ecology↗

bioRxiv2017

A single Vibrionales 16S rRNA oligotype dominates the intestinal microbiome in two geographically separated Atlantic cod populations

BackgroundHost-microbe interactions are particularly intriguing in Atlantic cod (Gadus morhua), as it lacks the MHC II complex involved in presentation of extracellular pathogens. Nonetheless, little is known about the diversity of its microbiome in natural populations. Here, we use 16S rRNA high-throughput sequencing to investigate the microbial community composition in gut content and mucosa of 22 adult individuals from two coastal populations in Norway, located 470 km apart.\n\nResultsWe identify a core microbiome of 23 OTUs (97% sequence similarity) in all individuals that comprises 93% of the total number of reads. The most abundant orders are classified as Vibrionales, Fusobacteriales, Clostridiales and Bacteroidales. While mucosal samples show significantly lower diversity than gut content samples, no differences in OTU community composition are observed between the two populations. The differential abundance of oligotypes within two common OTUs does reveal limited spatial segregation. Remarkably, the most abundant OTU consists of a single oligotype (order Vibrionales, genus Photobacterium) that represents nearly 50% of the reads in both locations.\n\nConclusionsOur results show that the intestinal bacterial community of two geographically separated coastal populations of Atlantic cod is dominated by a limited number of highly abundant 16S rRNA oligotypes shared by all specimens examined. The ubiquity of these oligotypes suggests that the northern coastal Atlantic cod gut microbiome is colonized by a limited number of species with excellent dispersal capabilities that are well suited to thrive in their host environment.

microbiology↗