Bacterial-Viral Interactions in Human Orodigestive and Female Genital Tract Cancers: A Summary of Epidemiologic and Laboratory Evidence

Infectious agents, including viruses, bacteria, fungi, and parasites, have been linked to pathogenesis of human cancers, whereas viruses and bacteria account for more than 99% of infection associated cancers. The human microbiome consists of not only bacteria, but also viruses and fungi. The microbiome co-residing in specific anatomic niches may modulate oncologic potentials of infectious agents in carcinogenesis. In this review, we focused on interactions between viruses and bacteria for cancers arising from the orodigestive tract and the female genital tract. We examined the interactions of these two different biological entities in the context of human carcinogenesis in the following three fashions: (1) direct interactions, (2) indirect interactions, and (3) no interaction between the two groups, but both acting on the same host carcinogenic pathways, yielding synergistic or additive effects in human cancers, e.g., head and neck cancer, liver cancer, colon cancer, gastric cancer, and cervical cancer. We discuss the progress in the current literature and summarize the mechanisms of host-viral-bacterial interactions in various human cancers. Our goal was to evaluate existing evidence and identify gaps in the knowledge for future directions in infection and cancer.

Theoretical Study of the Structural Stability, Chemical Reactivity, and Protein Interaction for NMP Compounds as Modulators of the Endocannabinoid System

The cannabinoid receptors (CB1/CB2) and the T-type calcium channels are involved in disorders associated with both physiological pain and depressive behaviors. Valuable pharmacological species carbazole derivatives such as the NMP-4, NMP-7, and NMP-181 (Neuro Molecular Production) regulate both biological entities. In this work, DFT calculations were performed to characterize theoretically their structural and chemical reactivity properties using the BP86/cc-pVTZ level of theory. The molecular orbital contributions and the chemical reactivity analysis reveal that a major participation of the carbazole group is in the donor-acceptor interactions of the NMP compounds. The DFT analysis on the NMP compounds provides insights into the relevant functional groups involved during the ligand-receptor interactions. Molecular docking analysis is used to reveal possible sites of interaction of the NMP compounds with the Cav3.2 calcium channel. The interaction energy values and reported experimental evidence indicate that the site denominated as “Pore-blocking”, which is formed mainly by hydrophobic residues and the T586 residue, is a probable binding site for the NMP compounds.

Phages in the Gut Ecosystem

Phages, short for bacteriophages, are viruses that specifically infect bacteria and are the most abundant biological entities on earth found in every explored environment, from the deep sea to the Sahara Desert. Phages are abundant within the human biome and are gaining increasing recognition as potential modulators of the gut ecosystem. For example, they have been connected to gastrointestinal diseases and the treatment efficacy of Fecal Microbiota Transplant. The ability of phages to modulate the human gut microbiome has been attributed to the predation of bacteria or the promotion of bacterial survival by the transfer of genes that enhance bacterial fitness upon infection. In addition, phages have been shown to interact with the human immune system with variable outcomes. Despite the increasing evidence supporting the importance of phages in the gut ecosystem, the extent of their influence on the shape of the gut ecosystem is yet to be fully understood. Here, we discuss evidence for phage modulation of the gut microbiome, postulating that phages are pivotal contributors to the gut ecosystem dynamics. We therefore propose novel research questions to further elucidate the role(s) that they have within the human ecosystem and its impact on our health and well-being.

Editorial for the Special Issue: The Role of the Virome in Health and Disease

Viruses are the most abundant biological entities on Earth, with an estimated total of 1031 virions [...]

Brief teaching experience facing COVID-19

<p>These questions and comments that genuinely arose in my remote classes with youngsters aged 15 to 18 showed me the impact of the pandemic on their way of thinking regarding a topic I have been explaining for years: VIRUSES. Now, these youngsters understood that answering the question they always had asked me every cycle (Are viruses alive or dead?) was irrelevant, and they focused on what really matters: How can something so small cause such an impact on the human lives? So, they understood that all tiny living beings, which they cannot see, are crucial to the balance of life and we do have the responsibility of making the least possible impact on that microbiological world. I realized that the pandemic had awoken interest in teenagers, and probably in all people, regarding viruses. From the agronomic point of view, I hope the minds of young men and women who are preparing to become future agronomists in Mexico, also become interested in phytopathogenic viruses, a somewhat forgotten area in the Mexican field. Thus, it is desirable for more virologists to be present to understand the role of these biological entities on an agricultural crop, in vectors and weeds. And maybe, in the mind of parasitologists would also be relevant to understand better the viruses, and the automatic approach for a plant with viruses on the field, not only would be eliminated them immediately. As an agronomist/phytopathologist, I understood the importance of viruses on plants in the few years I have been studying them, and not only because they cause diseases, but I have often seen that viruses “have learned” to coexist with plants without causing great harm to them. In fact, I dare to guarantee that some even help their host to survive adverse situations, although it is easier to claim it than to prove it scientifically. The current knowledge of microorganisms in the biome of the plant will soon help us recognize beneficial viruses. The same surely happens in viruses that are able to infect humans, but because they are invisible, we have focused on those that harm us, leaving a large scientific omission that must be explored. As an investigative professor, I explained to my worried and stressed students that we may have to accept that viruses are sometimes deadly, but sooner or later, with the help of scientists working on developing vaccines, this pandemic would pass. They then understood that, in order to survive this health crisis, they should better understand the viruses, know how and what they are made up of, how they are transmitted and how they can use the cells of their host to replicate and cause diseases. In this way they could make reasonable decisions that will benefit them and their families.</p>

Understanding the Function of a Locus Using the Knowledge Available at Single-Nucleotide Polymorphisms

Understanding the function of a locus is an issue in molecular biology. Although numerous molecular data have been generated in the last decades, it remains difficult to grasp how these data are related at a locus. In this study, we describe an analytical workflow that can solve this problem using the knowledge available at the single-nucleotide polymorphism (SNP) level. The underlying algorithm uses SNPs as connectors to link biological entities and identify correlations between them through a joint bioinformatics/statistics approach. We demonstrate its application in finding the mechanism whereby a mutation causes a phenotype and in revealing the path whereby a gene is regulated and impacts a phenotype. We translate our workflow into publicly available shell scripts. Our approach provides a basic framework to solve the information overload problem in biology surrounding the annotation of a locus and is a step toward repurposing GWAS data for new applications.

Separating Phages From Other Virus Families and Classifying the Different Phage Families By GI-Clusters

Background: Phages are the most abundant biological entities, but the commonly used clustering techniques are difficult to separate them from other virus families and classify the different phage families together.Results: This work uses GI-clusters to separate phages from other virus families and classify the different phage families, where GI-clusters are constructed by GI-features, GI-features are constructed by the togetherness with F-features, training data, MG-Euclidean and Icc-cluster algorithms, F-features are the frequencies of multiple-nucleotides that are generated from genomes of viruses, MG-Euclidean algorithm is able to put the nearest neighbors in the same mini-groups, and Icc-cluster algorithm put the distant samples to the different mini-clusters. For these viruses that the maximum element of their GI-features are in the same locations, they are put to the same GI-clusters, where the families of viruses in test data are identified by GI-clusters, and the families of GI-clusters are defined by viruses of training data.Conclusions: From analysis of 4 data sets that are constructed by the different family viruses, we demonstrate that GI-clusters are able to separate phages from other virus families, correctly classify the different phage families, and correctly predict the families of these unknown phages also.

Traits of a mussel transmissible cancer are reminiscent of a parasitic life style

Some cancers have evolved the ability to spread from host to host by transmission of cancerous cells. These rare biological entities can be considered parasites with a host-related genome. Still, we know little about their specific adaptation to a parasitic lifestyle. MtrBTN2 is one of the few lineages of transmissible cancers known in the animal kingdom. Reported worldwide, MtrBTN2 infects marine mussels. We isolated MtrBTN2 cells circulating in the hemolymph of cancerous mussels and investigated their phenotypic traits. We found that MtrBTN2 cells had remarkable survival capacities in seawater, much higher than normal hemocytes. With almost 100% cell survival over three days, they increase significantly their chances to infect neighboring hosts. MtrBTN2 also triggered an aggressive cancerous process: proliferation in mussels was ~ 17 times higher than normal hemocytes (mean doubling time of ~ 3 days), thereby favoring a rapid increase of intra-host population size. MtrBTN2 appears to induce host castration, thereby favoring resources re-allocation to the parasites and increasing the host carrying capacity. Altogether, our results highlight a series of traits of MtrBTN2 consistent with a marine parasitic lifestyle that may have contributed to the success of its persistence and dissemination in different mussel populations across the globe.

GraphOmics: an interactive platform to explore and integrate multi-omics data

Background An increasing number of studies now produce multiple omics measurements that require using sophisticated computational methods for analysis. While each omics data can be examined separately, jointly integrating multiple omics data allows for deeper understanding and insights to be gained from the study. In particular, data integration can be performed horizontally, where biological entities from multiple omics measurements are mapped to common reactions and pathways. However, data integration remains a challenge due to the complexity of the data and the difficulty in interpreting analysis results. Results Here we present GraphOmics, a user-friendly platform to explore and integrate multiple omics datasets and support hypothesis generation. Users can upload transcriptomics, proteomics and metabolomics data to GraphOmics. Relevant entities are connected based on their biochemical relationships, and mapped to reactions and pathways from Reactome. From the Data Browser in GraphOmics, mapped entities and pathways can be ranked, sorted and filtered according to their statistical significance (p values) and fold changes. Context-sensitive panels provide information on the currently selected entities, while interactive heatmaps and clustering functionalities are also available. As a case study, we demonstrated how GraphOmics was used to interactively explore multi-omics data and support hypothesis generation using two complex datasets from existing Zebrafish regeneration and Covid-19 human studies. Conclusions GraphOmics is fully open-sourced and freely accessible from https://graphomics.glasgowcompbio.org/. It can be used to integrate multiple omics data horizontally by mapping entities across omics to reactions and pathways. Our demonstration showed that by using interactive explorations from GraphOmics, interesting insights and biological hypotheses could be rapidly revealed.

HillTau: A fast, compact abstraction for model reduction in biochemical signaling networks

Signaling networks mediate many aspects of cellular function. The conventional, mechanistically motivated approach to modeling such networks is through mass-action chemistry, which maps directly to biological entities and facilitates experimental tests and predictions. However such models are complex, need many parameters, and are computationally costly. Here we introduce the HillTau form for signaling models. HillTau retains the direct mapping to biological observables, but it uses far fewer parameters, and is 100 to over 1000 times faster than ODE-based methods. In the HillTau formalism, the steady-state concentration of signaling molecules is approximated by the Hill equation, and the dynamics by a time-course tau. We demonstrate its use in implementing several biochemical motifs, including association, inhibition, feedforward and feedback inhibition, bistability, oscillations, and a synaptic switch obeying the BCM rule. The major use-cases for HillTau are system abstraction, model reduction, scaffolds for data-driven optimization, and fast approximations to complex cellular signaling.