Signal metrics analysis of oscillatory patterns in bacterial multi-omic networks

Abstract Motivation One of the branches of Systems Biology is focused on a deep understanding of underlying regulatory networks through the analysis of the biomolecules oscillations and their interplay. Synthetic Biology exploits gene or/and protein regulatory networks towards the design of oscillatory networks for producing useful compounds. Therefore, at different levels of application and for different purposes, the study of biomolecular oscillations can lead to different clues about the mechanisms underlying living cells. It is known that network-level interactions involve more than one type of biomolecule as well as biological processes operating at multiple omic levels. Combining network/pathway-level information with genetic information it is possible to describe well-understood or unknown bacterial mechanisms and organism-specific dynamics. Results Following the methodologies used in signal processing and communication engineering, a methodology is introduced to identify and quantify the extent of multi-omic oscillations. These are due to the process of multi-omic integration and depend on the gene positions on the chromosome. Ad hoc signal metrics are designed to allow further biotechnological explanations and provide important clues about the oscillatory nature of the pathways and their regulatory circuits. Our algorithms designed for the analysis of multi-omic signals are tested and validated on 11 different bacteria for thousands of multi-omic signals perturbed at the network level by different experimental conditions. Information on the order of genes, codon usage, gene expression and protein molecular weight is integrated at three different functional levels. Oscillations show interesting evidence that network-level multi-omic signals present a synchronized response to perturbations and evolutionary relations along taxa. Availability and implementation The algorithms, the code (in language R), the tool, the pipeline and the whole dataset of multi-omic signal metrics are available at: https://github.com/lodeguns/Multi-omicSignals. Supplementary information Supplementary data are available at Bioinformatics online.

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The Minimum Information about a Molecular Interaction CAusal STatement (MI2CAST)

Bioinformatics ◽

10.1093/bioinformatics/btaa622 ◽

2020 ◽

Cited By ~ 3

Author(s):

Vasundra Touré ◽

Steven Vercruysse ◽

Marcio Luis Acencio ◽

Ruth C Lovering ◽

Sandra Orchard ◽

...

Keyword(s):

Molecular Interaction ◽

Regulatory Networks ◽

Building Blocks ◽

Supplementary Information ◽

Biological Processes ◽

Causal Interaction ◽

End User ◽

Minimum Information ◽

Causal Statement ◽

In Cells

Abstract Motivation A large variety of molecular interactions occurs between biomolecular components in cells. When a molecular interaction results in a regulatory effect, exerted by one component onto a downstream component, a so-called ‘causal interaction’ takes place. Causal interactions constitute the building blocks in our understanding of larger regulatory networks in cells. These causal interactions and the biological processes they enable (e.g. gene regulation) need to be described with a careful appreciation of the underlying molecular reactions. A proper description of this information enables archiving, sharing and reuse by humans and for automated computational processing. Various representations of causal relationships between biological components are currently used in a variety of resources. Results Here, we propose a checklist that accommodates current representations, called the Minimum Information about a Molecular Interaction CAusal STatement (MI2CAST). This checklist defines both the required core information, as well as a comprehensive set of other contextual details valuable to the end user and relevant for reusing and reproducing causal molecular interaction information. The MI2CAST checklist can be used as reporting guidelines when annotating and curating causal statements, while fostering uniformity and interoperability of the data across resources. Availability and implementation The checklist together with examples is accessible at https://github.com/MI2CAST/MI2CAST Supplementary information Supplementary data are available at Bioinformatics online.

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State of the Art of Fuzzy Methods for Gene Regulatory Networks Inference

The Scientific World JOURNAL ◽

10.1155/2015/148010 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 5

Author(s):

Tuqyah Abdullah Al Qazlan ◽

Aboubekeur Hamdi-Cherif ◽

Chafia Kara-Mohamed

Keyword(s):

Gene Regulatory Networks ◽

Regulatory Networks ◽

Ad Hoc ◽

Cellular Level ◽

Biological Information ◽

Cellular Functions ◽

Fuzzy Methods ◽

Gene Regulatory ◽

Living Organisms ◽

Different Levels

To address one of the most challenging issues at the cellular level, this paper surveys the fuzzy methods used in gene regulatory networks (GRNs) inference. GRNs represent causal relationships between genes that have a direct influence, trough protein production, on the life and the development of living organisms and provide a useful contribution to the understanding of the cellular functions as well as the mechanisms of diseases. Fuzzy systems are based on handling imprecise knowledge, such as biological information. They provide viable computational tools for inferring GRNs from gene expression data, thus contributing to the discovery of gene interactions responsible for specific diseases and/orad hoccorrecting therapies. Increasing computational power and high throughput technologies have provided powerful means to manage these challenging digital ecosystems at different levels from cell to society globally. The main aim of this paper is to report, present, and discuss the main contributions of this multidisciplinary field in a coherent and structured framework.

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Reproducibility and reusability limitations in Regulatory Circuits: analysis and solutions

10.1101/2021.08.02.454723 ◽

2021 ◽

Author(s):

Marine Louarn ◽

Anne Siegel ◽

Thierry Fest ◽

Olivier Dameron ◽

Fabrice Chatonnet

Keyword(s):

Data Integration ◽

Regulatory Networks ◽

Cell Types ◽

Biological Data ◽

Google Scholar ◽

Cell Type ◽

Regulatory Circuits ◽

Cell Type Specific ◽

Different Levels

The Regulatory Circuits project is among the most recent and the most complete attempts to identify cell-type specific regulatory networks in Human. It is one of the largest efforts of public genomics data integration, based on data from the major consortia FANTOM5, ENCODE and Roadmap Epigenomics. This project is a main provider of biological data, cited more than 224 times (Google Scholar) and its resulting networks were used in at least 42 other articles. For such a general resource, reproducibility of both the outputs (regulation networks) and methods (data integration pipeline) is a major issue, since biological data are updated regularly. In addition, users may want to introduce new data into the Regulatory Circuits framework to provide networks about previously uncharacterized cell types or to add information about specific regulators, which require to re-execute the whole pipeline on the new data. In this article, we analyze the various factors limiting reproducibility of the Regulatory Circuits data and methods. Starting from a factual description of our understanding of the methods used in Regulatory Circuits, our contribution is two-fold: we propose (1) a characterization of the different levels of reusability, reproducibility and conceptual issues in the original workflow and (2) a new implementation of the workflow ensuring its consistency with the published description and allowing for an easier reuse and reproduction of the published outputs. Both are applicable beyond the case of Regulatory Circuits.

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Nonparametric Bayesian inference for perturbed and orthologous gene regulatory networks

Bioinformatics ◽

10.1093/bioinformatics/bts222 ◽

2012 ◽

Vol 28 (12) ◽

pp. i233-i241 ◽

Cited By ~ 38

Author(s):

Christopher A. Penfold ◽

Vicky Buchanan-Wollaston ◽

Katherine J. Denby ◽

David L. Wild

Keyword(s):

Time Series ◽

Transcription Factors ◽

Reverse Engineering ◽

Gene Regulatory Networks ◽

Regulatory Networks ◽

Supplementary Information ◽

Series Data ◽

Experimental Conditions ◽

Biological Studies ◽

Gene Regulatory

Abstract Motivation: The generation of time series transcriptomic datasets collected under multiple experimental conditions has proven to be a powerful approach for disentangling complex biological processes, allowing for the reverse engineering of gene regulatory networks (GRNs). Most methods for reverse engineering GRNs from multiple datasets assume that each of the time series were generated from networks with identical topology. In this study, we outline a hierarchical, non-parametric Bayesian approach for reverse engineering GRNs using multiple time series that can be applied in a number of novel situations including: (i) where different, but overlapping sets of transcription factors are expected to bind in the different experimental conditions; that is, where switching events could potentially arise under the different treatments and (ii) for inference in evolutionary related species in which orthologous GRNs exist. More generally, the method can be used to identify context-specific regulation by leveraging time series gene expression data alongside methods that can identify putative lists of transcription factors or transcription factor targets. Results: The hierarchical inference outperforms related (but non-hierarchical) approaches when the networks used to generate the data were identical, and performs comparably even when the networks used to generate data were independent. The method was subsequently used alongside yeast one hybrid and microarray time series data to infer potential transcriptional switches in Arabidopsis thaliana response to stress. The results confirm previous biological studies and allow for additional insights into gene regulation under various abiotic stresses. Availability: The methods outlined in this article have been implemented in Matlab and are available on request. Contact: [email protected] Supplementary Information: Supplementary data is available for this article.

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CorGAT: a tool for the functional annotation of SARS-CoV-2 genomes

Bioinformatics ◽

10.1093/bioinformatics/btaa1047 ◽

2020 ◽

Author(s):

Matteo Chiara ◽

Federico Zambelli ◽

Marco Antonio Tangaro ◽

Pietro Mandreoli ◽

David S Horner ◽

...

Keyword(s):

Functional Annotation ◽

Ad Hoc ◽

State Of The Art ◽

Supplementary Information ◽

Genomic Sequences ◽

Supplementary Data ◽

Evolutionary Patterns ◽

Genomic Variants ◽

Art Methods ◽

Available Resources

Abstract Summary While over 200 000 genomic sequences are currently available through dedicated repositories, ad hoc methods for the functional annotation of SARS-CoV-2 genomes do not harness all currently available resources for the annotation of functionally relevant genomic sites. Here, we present CorGAT, a novel tool for the functional annotation of SARS-CoV-2 genomic variants. By comparisons with other state of the art methods we demonstrate that, by providing a more comprehensive and rich annotation, our method can facilitate the identification of evolutionary patterns in the genome of SARS-CoV-2. Availabilityand implementation Galaxy http://corgat.cloud.ba.infn.it/galaxy; software: https://github.com/matteo14c/CorGAT/tree/Revision_V1; docker: https://hub.docker.com/r/laniakeacloud/galaxy_corgat. Supplementary information Supplementary data are available at Bioinformatics online.

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The Effect of pH, Ionic Strength and the Presence of PbII on the Formation of Calcium Carbonate from Homogenous Alkaline Solutions at Room Temperature

Minerals ◽

10.3390/min11070783 ◽

2021 ◽

Vol 11 (7) ◽

pp. 783

Author(s):

Fulvio Di Lorenzo ◽

Kay Steiner ◽

Sergey V. Churakov

Keyword(s):

Ionic Strength ◽

Deep Understanding ◽

Inhibitory Effect ◽

Alkaline Solutions ◽

Nucleation Kinetics ◽

Experimental Conditions ◽

Calcium Carbonates ◽

Natural Systems ◽

Geological Processes ◽

System Variables

Precipitation of calcium carbonates in aqueous systems is an important factor controlling various industrial, biological, and geological processes. In the first part of this study, the well-known titration approach introduced by Gebauer and coworkers in 2008 s used to obtain reliable experimental dataset for the deep understanding of CaCO3 nucleation kinetics in supersaturated solutions over a broad range of pH and ionic strength conditions. In the second part, the effect of impurities, i.e., 1 mol% of Pb2+, was assessed in the same range of experimental conditions. Divalent lead has been shown to have an inhibitory effect in all ranges of the conditions tested except for pH 8 and low ionic strength (≤0.15 mol/L). Future investigations might take advantage of the methodology and the data provided in this work to investigate the effect of other system variables. The investigation of all the major variables and the assessment of eventual synergic effects could improve our ability to predict the formation of CaCO3 in complex natural systems.

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Securing the future of statistics in Africa through National Strategies for the Development of Statistic

Statistical Journal of the IAOS ◽

10.3233/sji-200694 ◽

2020 ◽

Vol 36 ◽

pp. 15-25

Author(s):

Ben Kiregyera

Keyword(s):

Ad Hoc ◽

Lessons Learned ◽

Global Level ◽

African Countries ◽

Implementation Challenges ◽

Statistical Systems ◽

Development Agendas ◽

Different Levels ◽

Statistical Development

Adoption of development agendas at different levels – national, regional, continental, and global level – has led to an unprecedented increase in demand for official statistics. This increase has not only brought to the fore a litany of challenges facing National Statistical Systems (NSSs) in Africa but also it has created opportunities for strengthening statistical production and development. This paper underscores the need for countries to take full advantage of these opportunities and increase investments in statistics, undertake data innovation, and expand and diversify data ecosystems, leveraging on the foundations of the data revolution for sustainable development and in line with current international statistical frameworks. The paper posits that these improvements will not happen coincidentally nor through ad hoc, piecemeal and uncoordinated approaches. Rather they will happen through more systematic, coordinated and multi-sectoral approaches to statistical development. The National Strategy for the Development of Statistics (NSDS) is presented as a comprehensive and robust framework for building statistical capacity and turning around NSSs in African countries. The paper unpacks the NSDS; elaborates the NSDS processes including; mainstreaming sectors into the NSDS, the stages of the NSDS lifecycle and the role of leadership in the NSDS proces; highlights NSDS extension; presents the design and implementation challenges, and the key lessons learned from the NSDS processes in Africa in the last 15 years or so.

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Ribo-ODDR: Oligo design pipeline for experiment-specific rRNA depletion in ribo-seq

Bioinformatics ◽

10.1093/bioinformatics/btab171 ◽

2021 ◽

Author(s):

Ferhat Alkan ◽

Joana Silva ◽

Eric Pintó Barberà ◽

William J Faller

Keyword(s):

Ribosome Profiling ◽

Supplementary Information ◽

Experimental Conditions ◽

Computational Framework ◽

Rna Translation ◽

Rrna Depletion ◽

Selection For ◽

Nucleotide Resolution ◽

User Friendly ◽

Oligo Design

Abstract Motivation Ribosome Profiling (Ribo-seq) has revolutionized the study of RNA translation by providing information on ribosome positions across all translated RNAs with nucleotide-resolution. Yet several technical limitations restrict the sequencing depth of such experiments, the most common of which is the overabundance of rRNA fragments. Various strategies can be employed to tackle this issue, including the use of commercial rRNA depletion kits. However, as they are designed for more standardized RNAseq experiments, they may perform suboptimally in Ribo-seq. In order to overcome this, it is possible to use custom biotinylated oligos complementary to the most abundant rRNA fragments, however currently no computational framework exists to aid the design of optimal oligos. Results Here, we first show that a major confounding issue is that the rRNA fragments generated via Ribo-seq vary significantly with differing experimental conditions, suggesting that a “one-size-fits-all” approach may be inefficient. Therefore we developed Ribo-ODDR, an oligo design pipeline integrated with a user-friendly interface that assists in oligo selection for efficient experiment-specific rRNA depletion. Ribo-ODDR uses preliminary data to identify the most abundant rRNA fragments, and calculates the rRNA depletion efficiency of potential oligos. We experimentally show that Ribo-ODDR designed oligos outperform commercially available kits and lead to a significant increase in rRNA depletion in Ribo-seq. Availability Ribo-ODDR is freely accessible at https://github.com/fallerlab/Ribo-ODDR Supplementary information Supplementary data are available at Bioinformatics online.

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Countering Threats

International Journal of Cyber Warfare and Terrorism ◽

10.4018/ijcwt.2014040103 ◽

2014 ◽

Vol 4 (2) ◽

pp. 35-45

Author(s):

Margarita Jaitner

Keyword(s):

Social Media ◽

Law Enforcement ◽

Ad Hoc ◽

Physical Violence ◽

Deep Understanding ◽

Current Status ◽

Mobile Web ◽

Use Of Social Media ◽

Legal Frameworks ◽

High Level

The increased adoption of social media has presented security and law enforcement authorities with significant new challenges. For example, the Swedish Security Service (SÄPO) asserts that a large proportion of radicalization takes place in open fora online. Still, approaches to contain social media-driven challenges to security, particularly in democratic societies, remain little explored. Nonetheless, this type of knowledge may become relevant in European countries in the near future: Amongst other factors, the challenging economic situation has resulted in increased public discontent leading to emergence or manifestation of groups that seek to challenge the existing policies by almost any means. Use of social media multiplies the number of vectors that need law enforcement attention. First, a high level of social media adaption allows groups to reach and attract a wider audience. Unlike previously, many groups today consist of a large but very loosely connected network. This lack of cohesion can present a challenge for authorities, to identify emerging key actors and assess threat levels. Second, a high level of mobile web penetration has allowed groups to ad-hoc organize, amend plans and redirect physical activities. Third, the tool social media is as not exclusive to potential perpetrators of unlawful action, but is as well available to law enforcement authorities. Yet, efficient utilization of social media requires a deep understanding of its nature and a well-crafted, comprehensive approach. Acknowledging the broad functionality of social media, as well as its current status in the society, this article describes a model process for security authorities and law enforcement work with social media in general and security services work in particular. The process is cyclic and largely modular. It provides a set of goals and tasks for each stage of a potential event, rather than fixed activities. This allows authorities to adapt the process to individual legal frameworks and organization setups. The approach behind the process is holistic where social media is regarded as both source and destination of information. Ultimately, the process aims at efficiently and effectively mitigating the risk of virtual and physical violence.

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Genes Required for Aerial Growth, Cell Division, and Chromosome Segregation Are Targets of WhiA before Sporulation in Streptomyces venezuelae

mBio ◽

10.1128/mbio.00684-13 ◽

2013 ◽

Vol 4 (5) ◽

Cited By ~ 61

Author(s):

Matthew J. Bush ◽

Maureen J. Bibb ◽

Govind Chandra ◽

Kim C. Findlay ◽

Mark J. Buttner

Keyword(s):

Cell Division ◽

Chromosome Segregation ◽

Regulatory Networks ◽

Liquid Culture ◽

Biological Processes ◽

Streptomyces Venezuelae ◽

Content Type ◽

Master Regulators ◽

Aerial Growth ◽

Genes Encoding

ABSTRACTWhiA is a highly unusual transcriptional regulator related to a family of eukaryotic homing endonucleases. WhiA is required for sporulation in the filamentous bacteriumStreptomyces, but WhiA homologues of unknown function are also found throughout the Gram-positive bacteria. To better understand the role of WhiA inStreptomycesdevelopment and its function as a transcription factor, we identified the WhiA regulon through a combination of chromatin immunoprecipitation-sequencing (ChIP-seq) and microarray transcriptional profiling, exploiting a new model organism for the genus,Streptomyces venezuelae, which sporulates in liquid culture. The regulon encompasses ~240 transcription units, and WhiA appears to function almost equally as an activator and as a repressor. Bioinformatic analysis of the upstream regions of the complete regulon, combined with DNase I footprinting, identified a short but highly conserved asymmetric sequence, GACAC, associated with the majority of WhiA targets. Construction of a null mutant showed thatwhiAis required for the initiation of sporulation septation and chromosome segregation inS. venezuelae, and several genes encoding key proteins of theStreptomycescell division machinery, such asftsZ,ftsW, andftsK, were found to be directly activated by WhiA during development. Several other genes encoding proteins with important roles in development were also identified as WhiA targets, including the sporulation-specific sigma factor σWhiGand the diguanylate cyclase CdgB. Cell division is tightly coordinated with the orderly arrest of apical growth in the sporogenic cell, andfilP, encoding a key component of the polarisome that directs apical growth, is a direct target for WhiA-mediated repression during sporulation.IMPORTANCESince the initial identification of the genetic loci required forStreptomycesdevelopment, all of thebldandwhidevelopmental master regulators have been cloned and characterized, and significant progress has been made toward understanding the cell biological processes that drive morphogenesis. A major challenge now is to connect the cell biological processes and the developmental master regulators by dissecting the regulatory networks that link the two. Studies of these regulatory networks have been greatly facilitated by the recent introduction ofStreptomyces venezuelaeas a new model system for the genus, a species that sporulates in liquid culture. Taking advantage ofS. venezuelae, we have characterized the regulon of genes directly under the control of one of these master regulators, WhiA. Our results implicate WhiA in the direct regulation of key steps in sporulation, including the cessation of aerial growth, the initiation of cell division, and chromosome segregation.

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