Biology subjects

Pettersen, J. P.

Publications and source records attributed to Pettersen, J. P..

5 recordsLinked to original sources

bioRxiv2023

Genome-scale metabolic models reveal determinants of phenotypic differences in non-Saccharomyces yeasts

BackgroundUse of alternative non-Saccharomyces yeasts in wine and beer brewing has gained more attention the recent years. This is both due to the desire to obtain a wider variety of flavours in the product and to reduce the final alcohol content. Given the metabolic differences between the yeast species, we wanted to account for some of the differences by using in silico models. ResultsWe created and studied genome-scale metabolic models of five different non-Saccharomyces species using an automated processes. These were: Metschnikowia pulcherrima, Lachancea thermotolerans, Hanseniaspora osmophila and Kluyveromyces lactis. Using the models, we predicted that M. pulcherrima, when compared to the other species, conducts more respiration and thus produces less fermentation products, a finding which agrees with experimental data. Complex I of the electron transport chain was to be present in M. pulcherrima, but absent in the others. The predicted importance of Complex I was diminished when we incorporated constraints on the amount of enzymatic protein, as this shifts the metabolism towards fermentation. ConclusionsOur results suggest that Complex I in the electron transport chain is a key differentiator between Metschnikowia pulcherrima and the other yeasts considered. Yet, more annotations and experimental data have the potential to improve model quality in order to increase fidelity and confidence in these results. Further experiments should be conducted to confirm the in vivo effect of Complex I in M. pulcherrima and its respiratory metabolism.

systems biology↗

bioRxiv2022

Bayesian and evolutionary temperature dependent genome-scale models display alternative optima due to insufficient constraints

The metabolism of all living organisms is dependent on temperature, and therefore, having a good method to predict temperature effects at a system level is of importance. A recently developed Bayesian computational framework for enzyme and temperature constrained genome-scale models (etcGEM) predicts the temperature dependence of an organisms metabolic network from thermodynamic properties of the metabolic enzymes, markedly expanding the scope and applicability of constraint-based metabolic modelling. Here, we show that the Bayesian calculation method for inferring parameters for an etcGEM is unstable and unable to estimate the posterior distribution. The Bayesian calculation method assumes that the posterior distribution is unimodal, and thus fails due to the multimodality of the problem. To remedy this problem, we developed an evolutionary algorithm which is able to obtain a diversity of solutions in this multimodal parameter space. We quantified the phenotypic consequences on six metabolic network signature reactions of the different parameter solutions resulting from use of the evolutionary algorithm. While two of these reactions showed little phenotypic variation between the solutions, the remainder displayed huge variation in flux-carrying capacity. This result indicates that the model is underdetermined given current experimental data and that more data is required to narrow down the model predictions. Finally, we made improvements to the software to reduce the running time of the parameter set evaluations by a factor of 8.5, allowing for obtaining results faster and with less computational resources.

systems biology↗

bioRxiv2021

csdR, an R package for differential co-expression analysis

BackgroundDifferential co-expression network analysis has become an important tool to gain understanding of biological phenotypes and diseases. The CSD algorithm is a method to generate differential co-expression networks by comparing gene co-expressions from two different conditions. Each of the gene pairs is assigned conserved (C), specific (S) and differentiated (D) scores based on the co-expression of the gene pair between the two conditions. The result of the procedure is a network where the nodes are genes and the links are the gene pairs with the highest C-, S-, and D-scores. However, the existing CSD-implementations suffer from poor computational performance, difficult user procedures and lack of documentation. ResultsWe created the R-package csdR aimed at reaching good performance together with ease of use, sufficient documentation, and with the ability to play well with other tools for data analysis. csdR was benchmarked on a realistic dataset with 20, 645 genes. After verifying that the chosen number of iterations gave sufficient robustness, we tested the performance against the two existing CSD implementations. csdR was superior in performance to one of the implementations, whereas the other did not run. Our implementation can utilize multiple processing cores. However, we were unable to achieve more than [~] 2.7 parallel speedup with saturation reached at about 10 cores. ConclusionsThe results suggest that csdR is a useful tool for differential co-expression analysis and is able to generate robust results within a workday on datasets of realistic sizes when run on a workstation or compute server.

systems biology↗

bioRxiv2021

Robust bacterial co-occurence community structures are independent of r- and K-selection history

Selection for bacteria which are K-strategists instead of r-strategists has been shown to improve fish health and survival in aquaculture. We considered an experiment where microcosms were inoculated with natural seawater and the selection regime was switched from K-selection (by continuous feeding) to r-selection (by pulse feeding) and vice versa. We found the networks of significant co-occurrences to contain clusters of taxonomically related bacteria having positive associations. Comparing this with the time dynamics, we found that the clusters most likely were results of similar niche preferences of the involved bacteria. In particular, the distinction between r- or K-strategists was evident. Each selection regime seemed to give rise to a specific pattern, to which the community converges regardless of its prehistory. Furthermore, the results proved robust to parameter choices in the analysis, such as the filtering threshold, level of random noise, replacing absolute abundances with relative abundances, and the choice of similarity measure. Even though our data and approaches cannot directly predict ecological interactions, our approach provides insights on how the selection regime affects the composition and workings of the microbial community, providing a basis for aquaculture experiments targeted at eliminating opportunistic fish pathogens.

ecology↗

bioRxiv2019

Hairpin: a tool for predicting structural non-coding RNA genes ab initio

BackgroundStructural RNA genes play important and various roles in gene expression and its regulation. Finding such RNA genes in a genome poses a challenge, which in most cases is solved by homology approaches. Ab intio methods for prediction exist, but are not that much explored.\n\nResultsWe introduce hairpin which identify potential structural RNA genes only based on the sequence. We use the algorithm to predict RNA genes in Escherichia coli K-12. When looking at very short regions of the genome, we do not get results differing very much from a random shuffling of the genome. However, at longer stretches it is a clear biological signal. It turns out that none of the regions predicted to code for RNA genes have such an annotation in literature.\n\nConclusionsArbitrary DNA sequences seem to give rise to transcripts with secondary structures similar to real ncRNA. We therefore conclude that exclusively looking at secondary structure base-parings is in general a futile approach.

bioinformatics↗