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Benso, A.

Publications and source records attributed to Benso, A..

5 recordsLinked to original sources

On the state of protein function prediction: a report on the fourth CAFA challenge

BackgroundThe Critical Assessment of Functional Annotation (CAFA) is a community effort held to understand the field of computational protein function prediction. Every three years, since 2010, the organizers initiate an experiment to collect function predictions on a large set of proteins and then evaluate the performance of predicting methods on a subset of proteins that have accumulated experimental annotations between the submission deadline and the evaluation time. CAFA provides an independent and rigorous assessment of the current state of the art, thus leveling the playing field, highlighting successes, revealing bottlenecks, and offering a forum for the exchange of ideas in protein science. Here, we report the results of the fourth CAFA experiment (CAFA4). ResultsCAFA4 featured the participation of 148 methods from 70 research groups on a total of 46,205 unique proteins over a 5-year annotation accumulation phase, the longest in any CAFA. In a comparison across CAFA2-CAFA4 methods, the prediction of Gene Ontology (GO) terms has clearly improved across all three GO aspects and traditional evaluation settings. While not achieving the first rank, several CAFA2 and CAFA3 methods featured in the top ten methods in many evaluations, suggesting that earlier methods still hold relevance. The performance is weaker in the newly introduced "partial knowledge" evaluation category (proteins with experimental annotations before submission deadline that gained additional annotations in the same GO aspect during the annotation accumulation phase), highlighting the need for a new class of methods. The rankings of the methods were stable over the years in traditional evaluation settings, but less so in the new partial knowledge evaluation. Overall, the field continues to progress with some influx of new participants. Sustained efforts will be necessary to substantially advance it.

bioinformatics↗

Systems-level analysis identifies protein-RNA interactions contributing to autotrophy of Clostridium autoethanogenum

Burning fossil fuels drives climate change with detrimental consequences on humankind while waste accumulation from increasing consumption threatens biosustainability globally. Gas fermentation enables to recycle carbon oxides (CO and CO2) from industrial waste gases and gasified waste into value-added products using gas-fermenting microbes, namely acetogens. However, our limited understanding of gene function and metabolic regulation is hindering rational engineering of acetogen cell factories. In this work, we identified, for the first time in acetogens, genome-wide protein-RNA interactions contributing to autotrophy in the model-acetogen Clostridium autoethanogenum by combining steady-state chemostat cultivation, functional genomics, and computational methods. We first detected limited and uncoupled transcriptional and translational regulation between autotrophy and heterotrophy. Rigorous mapping of genome-wide transcriptional architecture revealed both differential usage and signal strength of transcriptional start and termination sites between genes and growth substrates. We then used computational tools to reconstruct protein-RNA interactions for differentially regulated genes predicting 14 trans-acting regulatory RNA-binding proteins (RBPs) involved in post-transcriptional regulation and contributing to autotrophy. Most RBPs, two of which are translationally regulated, perform RNA modifications and regulate mRNA stability while others target translation-related genes. Our work provides valuable knowledge for metabolic engineering of acetogens and potentially contributes towards understanding primordial life on Earth.

systems biology↗

Spectracular: minimizing spectral overlap in multicolor flow cytometry experiments

Selecting fluorochromes for polychromatic panels for flow cytometry is complex and time-consuming. Poorly designed panels can result in overlap between the emission spectra of the different fluorochromes, making their signals difficult to separate. While assessing all possible panels is simple to do programmatically, the combinatorial complexity of most real world problems renders brute force computation impractical. Here we present a novel complexity optimization algorithm for fast design of minimal spectral overlap fluorochrome combinations. To aid researchers in designing fluorochrome panels we implemented the algorithm in a web server, Spectracular, that also considers instrument laser configuration and allows users to define various constraints related to antibody-fluorochrome availability and marker co-expression.

bioinformatics↗

Nets-within-nets for modeling emergent patterns in ontogeneticprocesses

Ontogenesis is the development of an organism from its earliest stage to maturity, including homeostasis maintenance throughout adulthood despite environmental perturbations. Almost all cells of a multicellular organism share the same genomic information. Nevertheless, phenotypic diversity and complex supra-cellular architectures emerge at every level, starting from tissues and organs. This is possible thanks to a robust and dynamic interplay of regulative mechanisms. To study ontogenesis, it is necessary to consider different levels of regulation, both genetic and epigenetic. Each cell undergoes a specific path across a landscape of possible regulative states affecting both its structure and its functions during development. This paper proposes using the Nets-Within-Nets formalism, which combines Petri Nets simplicity with the capability to represent and simulate the interplay between different layers of regulation connected by non-trivial and context-dependent hierarchical relations. In particular, this work introduces a modeling strategy based on Nets-Within-Nets that can model several critical processes involved in ontogenesis. Moreover, it presents a case study focusing on the first phase of Vulval Precursor Cells specification in C. Elegans. The case study shows that the proposed model can simulate the emergent morphogenetic pattern corresponding to the observed developmental outcome of that phase, in both the physiological case and different mutations. The model presented in the results section is available online at https://github.com/sysbio-polito/NWN_CElegans_VPC_model/

systems biology↗

Beyond Homology Transfer: Deep Learning for Automated Annotation of Proteins

Accurate annotation of protein functions is important for a profound understanding of molecular biology. A large number of proteins remain uncharacterized because of the sparsity of available supporting information. For a large set of uncharacterized proteins, the only type of information available is their amino acid sequence. In this paper, we propose DeepSeq - a deep learning architecture - that utilizes only the protein sequence information to predict its associated functions. The prediction process does not require handcrafted features; rather, the architecture automatically extracts representations from the input sequence data. Results of our experiments with DeepSeq indicate significant improvements in terms of prediction accuracy when compared with other sequence-based methods. Our deep learning model achieves an overall validation accuracy of 86.72%, with an F1 score of 71.13%. Moreover, using the automatically learned features and without any changes to DeepSeq, we successfully solved a different problem i.e. protein function localization, with no human intervention. Finally, we discuss how this same architecture can be used to solve even more complicated problems such as prediction of 2D and 3D structure as well as protein-protein interactions.

bioinformatics↗