The functional determinants in the organization of bacterial genomes

2020 ◽  
Author(s):  
Zhaoqian Liu ◽  
Jingtong Feng ◽  
Bin Yu ◽  
Qin Ma ◽  
Bingqiang Liu
Keyword(s):  
Computational Models ◽  
Bacterial Genomes ◽  
Cellular Processes ◽  
Local Structures ◽  
Disease Mechanisms ◽  
Challenges And Opportunities ◽  
Genomic Studies ◽  
Primary Focus ◽  
Organizational Mechanisms ◽  
Transcription And Replication

Abstract Bacterial genomes are now recognized as interacting intimately with cellular processes. Uncovering organizational mechanisms of bacterial genomes has been a primary focus of researchers to reveal the potential cellular activities. The advances in both experimental techniques and computational models provide a tremendous opportunity for understanding these mechanisms, and various studies have been proposed to explore the organization rules of bacterial genomes associated with functions recently. This review focuses mainly on the principles that shape the organization of bacterial genomes, both locally and globally. We first illustrate local structures as operons/transcription units for facilitating co-transcription and horizontal transfer of genes. We then clarify the constraints that globally shape bacterial genomes, such as metabolism, transcription and replication. Finally, we highlight challenges and opportunities to advance bacterial genomic studies and provide application perspectives of genome organization, including pathway hole assignment and genome assembly and understanding disease mechanisms.

scholarly journals The first 10 years of the international coordination network for standards in systems and synthetic biology (COMBINE)

2020 ◽  
Vol 17 (2-3) ◽  
Author(s):  
Dagmar Waltemath ◽  
Martin Golebiewski ◽  
Michael L Blinov ◽  
Padraig Gleeson ◽  
Henning Hermjakob ◽  
...  
Keyword(s):  
Synthetic Biology ◽  
Data Model ◽  
Computational Models ◽  
Life Sciences ◽  
The Past ◽  
Challenges And Opportunities ◽  
Stakeholder Workshop ◽  
Software Engineers ◽  
Future Work ◽  
Modeling In Biology

AbstractThis paper presents a report on outcomes of the 10th Computational Modeling in Biology Network (COMBINE) meeting that was held in Heidelberg, Germany, in July of 2019. The annual event brings together researchers, biocurators and software engineers to present recent results and discuss future work in the area of standards for systems and synthetic biology. The COMBINE initiative coordinates the development of various community standards and formats for computational models in the life sciences. Over the past 10 years, COMBINE has brought together standard communities that have further developed and harmonized their standards for better interoperability of models and data. COMBINE 2019 was co-located with a stakeholder workshop of the European EU-STANDS4PM initiative that aims at harmonized data and model standardization for in silico models in the field of personalized medicine, as well as with the FAIRDOM PALs meeting to discuss findable, accessible, interoperable and reusable (FAIR) data sharing. This report briefly describes the work discussed in invited and contributed talks as well as during breakout sessions. It also highlights recent advancements in data, model, and annotation standardization efforts. Finally, this report concludes with some challenges and opportunities that this community will face during the next 10 years.

scholarly journals Adult Precision Medicine: Learning from the Past to Enhance the Future

2020 ◽  
Author(s):  
Ashley Ghiaseddin ◽  
Lan B Hoang Minh ◽  
Michalina Janiszewska ◽  
David Shin ◽  
Wolfgang Wick ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Precision Medicine ◽  
Historical Context ◽  
Pediatric Brain Tumors ◽  
Significant Heterogeneity ◽  
Future Success ◽  
Challenges And Opportunities ◽  
Genomic Studies ◽  
Patient Advocates ◽  
Molecular Therapies

Abstract Despite therapeutic advances for other malignancies, gliomas remain challenging solid tumors to treat. Complete surgical resection is nearly impossible due to gliomas’ diffuse infiltrative nature, and treatment is hampered by restricted access to the tumors due to limited transport across the blood-brain barrier (BBB). Recent advances in genomic studies and next-generation sequencing techniques have led to a better understanding of gliomas and identification of potential aberrant signaling pathways. Targeting the specific genomic abnormalities via novel molecular therapies has opened a new avenue in the management of gliomas, with encouraging results in preclinical studies and early clinical trials. However, molecular characterization of gliomas revealed the significant heterogeneity, which poses a challenge for targeted therapeutic approaches. In this context, leading neuro-oncology researchers and clinicians, industry innovators, and patient advocates convened at the inaugural annual Remission Summit held in Orlando, FL in February 2019 to discuss the latest advances in immunotherapy and precision medicine approaches for the treatment of adult and pediatric brain tumors and outline the unanswered questions, challenges, and opportunities that lay ahead for advancing the duration and quality of life for patients with brain tumors. Here, we provide historical context for precision medicine in other cancers, present emerging approaches for gliomas, discuss their limitations, and outline the steps necessary for future success. We focus on the advances in small molecule targeted therapy, as the use of immunotherapy as an emerging precision medicine modality for glioma treatment has recently been reviewed by our colleagues

scholarly journals Tandem Repeats in Bacillus: Unique Features and Taxonomic Distribution

2021 ◽  
Vol 22 (10) ◽  
pp. 5373
Author(s):  
Juan A. Subirana ◽  
Xavier Messeguer
Keyword(s):  
Tandem Repeats ◽  
Bacterial Species ◽  
Individual Species ◽  
Large Set ◽  
Bacterial Genomes ◽  
Rna Molecules ◽  
Variable Sequence ◽  
Repeat Size ◽  
Genomic Studies ◽  
Dna Tandem Repeats

Little is known about DNA tandem repeats across prokaryotes. We have recently described an enigmatic group of tandem repeats in bacterial genomes with a constant repeat size but variable sequence. These findings strongly suggest that tandem repeat size in some bacteria is under strong selective constraints. Here, we extend these studies and describe tandem repeats in a large set of Bacillus. Some species have very few repeats, while other species have a large number. Most tandem repeats have repeats with a constant size (either 52 or 20–21 nt), but a variable sequence. We characterize in detail these intriguing tandem repeats. Individual species have several families of tandem repeats with the same repeat length and different sequence. This result is in strong contrast with eukaryotes, where tandem repeats of many sizes are found in any species. We discuss the possibility that they are transcribed as small RNA molecules. They may also be involved in the stabilization of the nucleoid through interaction with proteins. We also show that the distribution of tandem repeats in different species has a taxonomic significance. The data we present for all tandem repeats and their families in these bacterial species will be useful for further genomic studies.

scholarly journals Eukaryotic systems broaden the scope of synthetic biology

2009 ◽  
Vol 187 (5) ◽  
pp. 589-596 ◽  
Author(s):  
Karmella A. Haynes ◽  
Pamela A. Silver
Keyword(s):  
Synthetic Biology ◽  
Nucleic Acids ◽  
Cell Biology ◽  
Cell Behavior ◽  
Cellular Functions ◽  
Complex Cells ◽  
Cellular Processes ◽  
Challenges And Opportunities ◽  
Foundational Work ◽  
Biology Research

Synthetic biology aims to engineer novel cellular functions by assembling well-characterized molecular parts (i.e., nucleic acids and proteins) into biological “devices” that exhibit predictable behavior. Recently, efforts in eukaryotic synthetic biology have sprung from foundational work in bacteria. Designing synthetic circuits to operate reliably in the context of differentiating and morphologically complex cells presents unique challenges and opportunities for progress in the field. This review surveys recent advances in eukaryotic synthetic biology and describes how synthetic systems can be linked to natural cellular processes in order to manipulate cell behavior and to foster new discoveries in cell biology research.

scholarly journals The Presence and Localization of G-Quadruplex Forming Sequences in the Domain of Bacteria

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1711 ◽  
Author(s):  
Martin Bartas ◽  
Michaela Čutová ◽  
Václav Brázda ◽  
Patrik Kaura ◽  
Jiří Šťastný ◽  
...  
Keyword(s):  
Regulatory Sequences ◽  
Bacterial Genomes ◽  
Dna Structures ◽  
Cellular Processes ◽  
G Quadruplex ◽  
Data Point ◽  
Functional Relevance

The role of local DNA structures in the regulation of basic cellular processes is an emerging field of research. Amongst local non-B DNA structures, the significance of G-quadruplexes was demonstrated in the last decade, and their presence and functional relevance has been demonstrated in many genomes, including humans. In this study, we analyzed the presence and locations of G-quadruplex-forming sequences by G4Hunter in all complete bacterial genomes available in the NCBI database. G-quadruplex-forming sequences were identified in all species, however the frequency differed significantly across evolutionary groups. The highest frequency of G-quadruplex forming sequences was detected in the subgroup Deinococcus-Thermus, and the lowest frequency in Thermotogae. G-quadruplex forming sequences are non-randomly distributed and are favored in various evolutionary groups. G-quadruplex-forming sequences are enriched in ncRNA segments followed by mRNAs. Analyses of surrounding sequences showed G-quadruplex-forming sequences around tRNA and regulatory sequences. These data point to the unique and non-random localization of G-quadruplex-forming sequences in bacterial genomes.

scholarly journals Longitudinal samples of bacterial genomes potentially bias evolutionary analyses

2017 ◽  
Author(s):  
B.J. Arnold ◽  
W.P. Hanage
Keyword(s):  
Genomic Data ◽  
Real Data ◽  
Sampling Bias ◽  
Bacterial Genomes ◽  
Clock Rate ◽  
Rare Mutations ◽  
Constant Size ◽  
Population Genomic ◽  
Genomic Studies ◽  
Longitudinal Sampling

AbstractSamples of bacteria collected over a period of time are attractive for several reasons, including the ability to estimate the molecular clock rate and to detect fluctuations in allele frequencies over time. However, longitudinal datasets are occasionally used in analyses that assume samples were collected contemporaneously. Using both simulations and genomic data from Neisseria gonorrhoeae, Streptococcus mutans, Campylobacter jejuni, and Helicobacter pylori, we show that longitudinal samples (spanning more than a decade in real data) may suffer from considerable bias that inflates estimates of recombination and the number of rare mutations in a sample of genomic sequences. While longitudinal data are frequently accounted for using the serial coalescent, many studies use other programs or metrics, such as Tajima’s D, that are sensitive to these sampling biases and contain genomic data collected across many years. Notably, longitudinal samples from a population of constant size may exhibit evidence of exponential growth. We suggest that population genomic studies of bacteria should routinely account for temporal diversity in samples or provide evidence that longitudinal sampling bias does not affect conclusions.

scholarly journals Interactive Multiresolution Visualization of Cellular Network Processes

2019 ◽  
Author(s):  
Oscar O. Ortega ◽  
Carlos F. Lopez
Keyword(s):  
Computational Models ◽  
Dynamic Network ◽  
Cellular Systems ◽  
Biochemical Network ◽  
Mitochondrial Outer Membrane ◽  
Cellular Processes ◽  
Detection Algorithms ◽  
Mitochondrial Outer Membrane Permeabilization ◽  
Extrinsic Apoptosis ◽  
Dynamic Execution

AbstractComputational models of network-driven processes have become a standard to explain cellular systems-level behavior and predict cellular responses to perturbations. Modern models can span a broad range of biochemical reactions and species that, in principle, comprise the complexity of dynamic cellular processes. Visualization plays a central role in the analysis of biochemical network processes to identify patterns that arise from model dynamics and perform model exploratory analysis. However, most existing visualization tools are limited in their capabilities to facilitate mechanism exploration of large, dynamic, and complex models. Here, we present PyViPR, a visualization tool that provides researchers static and dynamic representations of biochemical network processes within a Python-based Literate Programming environment. PyViPR embeds network visualizations on Jupyter notebooks, thus facilitating integration with Python modeling, simulation, and analysis workflows. To present the capabilities of PyViPR, we explore execution mechanisms of extrinsic apoptosis in HeLa cells. We show how community-detection algorithms can identify groups of molecular species that represent key biological regulatory functions and simplify the apoptosis network by placing those groups into interactively collapsible nodes. We then show how dynamic execution of a signal, under different kinetic parameter sets that fit the experimental data equally well, exhibit significantly different signal-execution modes in mitochondrial outer-membrane permeabilization – the point of no return in extrinsic apoptosis execution. Therefore, PyViPR aids the conceptual understanding of dynamic network processes and accelerates hypothesis generation for further testing and validation.

scholarly journals The ‘Digital Twin’ to enable the vision of precision cardiology

2020 ◽  
Vol 41 (48) ◽  
pp. 4556-4564 ◽  
Author(s):  
Jorge Corral-Acero ◽  
Francesca Margara ◽  
Maciej Marciniak ◽  
Cristobal Rodero ◽  
Filip Loncaric ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Computational Models ◽  
Cardiovascular Medicine ◽  
Cardiovascular Research ◽  
Digital Twin ◽  
Current Health ◽  
Diagnosis And Prognosis ◽  
Current Health Status ◽  
Model Predictions ◽  
Challenges And Opportunities

Abstract Providing therapies tailored to each patient is the vision of precision medicine, enabled by the increasing ability to capture extensive data about individual patients. In this position paper, we argue that the second enabling pillar towards this vision is the increasing power of computers and algorithms to learn, reason, and build the ‘digital twin’ of a patient. Computational models are boosting the capacity to draw diagnosis and prognosis, and future treatments will be tailored not only to current health status and data, but also to an accurate projection of the pathways to restore health by model predictions. The early steps of the digital twin in the area of cardiovascular medicine are reviewed in this article, together with a discussion of the challenges and opportunities ahead. We emphasize the synergies between mechanistic and statistical models in accelerating cardiovascular research and enabling the vision of precision medicine.

Narratives of Syrian refugee women in Lebanon: Gender stereotypes and resilience in language practices

2020 ◽  
Vol 17 (6) ◽  
pp. 781-798
Author(s):  
Marya Initia Yammine
Keyword(s):  
Gender Stereotypes ◽  
Syrian Refugees ◽  
Syrian Crisis ◽  
Refugee Women ◽  
Syrian Refugee ◽  
Challenges And Opportunities ◽  
Per Capita ◽  
Primary Focus ◽  
And Coping ◽  
Ways Of Life

Now in its ninth year, the Syrian crisis remains the largest humanitarian and displacement emergency of our time. Hundreds of thousands of people have lost their lives, while millions more have fled the country, undertaking exhausting journeys in search for safety in neighboring countries. However, when they arrive, challenges are far from over as they have to adapt to new ways of life. With more than one million Syrian refugees, Lebanon hosts the largest concentration of refugees per capita, globally. This study offers an in-depth look into Syrian refugees’ livelihoods and coping strategies and an attempt to explore whether gender stereotypes have been influenced by forced displacement. In this context, qualitative research was conducted between April and July 2019 with 60 Syrian refugee female heads of households in Akkar and North Lebanon, whose ages ranged from 25 to 35. The primary focus is to analyze the words and expressions used by refugee women themselves to describe the challenges and opportunities they face, both as women and as refugees, and how far these affect their gender roles.

scholarly journals Nanobodies Right in the Middle: Intrabodies as Toolbox to Visualize and Modulate Antigens in the Living Cell

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1701
Author(s):  
Teresa R. Wagner ◽  
Ulrich Rothbauer
Keyword(s):  
Real Time ◽  
New Technologies ◽  
Living Cells ◽  
Dynamic Interactions ◽  
Post Translational Modifications ◽  
Cellular Processes ◽  
Disease Mechanisms ◽  
Cellular Diagnostics ◽  
Intracellular Binding ◽  
Cellular Components

In biomedical research, there is an ongoing demand for new technologies to elucidate disease mechanisms and develop novel therapeutics. This requires comprehensive understanding of cellular processes and their pathophysiology based on reliable information on abundance, localization, post-translational modifications and dynamic interactions of cellular components. Traceable intracellular binding molecules provide new opportunities for real-time cellular diagnostics. Most prominently, intrabodies derived from antibody fragments of heavy-chain only antibodies of camelids (nanobodies) have emerged as highly versatile and attractive probes to study and manipulate antigens within the context of living cells. In this review, we provide an overview on the selection, delivery and usage of intrabodies to visualize and monitor cellular antigens in living cells and organisms. Additionally, we summarize recent advances in the development of intrabodies as cellular biosensors and their application to manipulate disease-related cellular processes. Finally, we highlight switchable intrabodies, which open entirely new possibilities for real-time cell-based diagnostics including live-cell imaging, target validation and generation of precisely controllable binding reagents for future therapeutic applications.

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