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Genome heterogeneity drives the evolution of species [article]

Mattia Miotto, Lorenzo Monacelli
2019 arXiv   pre-print
Most of the DNA that composes a complex organism is non-coding and defined as junk. Even the coding part is composed of genes that affect the phenotype differently. Therefore, a random mutation has an effect on the specimen fitness that strongly depends on the DNA region where it occurs. Such heterogeneous composition should be linked to the evolutionary process. However, the way is still unknown. Here, we study a minimal model for the evolution of an ecosystem where two antagonist species
more » ... gle for survival on a lattice. Each specimen possesses a toy genome, encoding for its phenotype. The gene pool of populations changes in time due to the effect of random mutations on genes (entropic force) and of interactions with the environment and between individuals (natural selection). We prove that the relevance of each gene in the manifestation of the phenotype is a key feature for evolution. In the presence of a uniform gene relevance, a mutational meltdown is observed. Natural selection acts quenching the ecosystem in a non-equilibriumstate that slowly drifts, decreasing the fitness and leading to the extinction of the species. Conversely, if a specimen is provided with a heterogeneous gene relevance, natural selection wins against entropic forces, and the species evolves increasing its fitness. We finally show that heterogeneity together with spatial correlations is responsible for spontaneous sympatric speciation.
arXiv:1912.01444v1 fatcat:a2pzuwncj5h7vfvmnp6qnaflde

Competing endogenous RNA crosstalk at system level [article]

Mattia Miotto, Enzo Marinari, Andrea De Martino
2019 arXiv   pre-print
microRNAs (miRNAs) regulate gene expression at post-transcriptional level by repressing target RNA molecules. Competition to bind miRNAs tends in turn to correlate their targets, establishing effective RNA-RNA interactions that can influence expression levels, buffer fluctuations and promote signal propagation. Such a potential has been characterized mathematically for small motifs both at steady state and away from stationarity. Experimental evidence, on the other hand, suggests that competing
more » ... endogenous RNA (ceRNA) crosstalk is rather weak. Extended miRNA-RNA networks could however favour the integration of many crosstalk interactions, leading to significant large-scale effects in spite of the weakness of individual links. To clarify the extent to which crosstalk is sustained by the miRNA interactome, we have studied its emergent systemic features in silico in large-scale miRNA-RNA network reconstructions. We show that, although generically weak, system-level crosstalk patterns (i) are enhanced by transcriptional heterogeneities, (ii) can achieve high-intensity even for RNAs that are not co-regulated, (iii) are robust to variability in transcription rates, and (iv) are significantly non-local, i.e. correlate weakly with miRNA-RNA interaction parameters. Furthermore, RNA levels are generically more stable when crosstalk is strongest. As some of these features appear to be encoded in the network's topology, crosstalk may functionally be favoured by natural selection. These results suggest that, besides their repressive role, miRNAs mediate a weak but resilient and context-independent network of cross-regulatory interactions that interconnect the transcriptome, stabilize expression levels and support system-level responses.
arXiv:1910.09256v1 fatcat:3pzszz2om5celiyvkdwawhvylq

Entropy evaluation sheds light on ecosystem complexity [article]

Mattia Miotto, Lorenzo Monacelli
2018 arXiv   pre-print
Preserving biodiversity and ecosystem stability is a challenge that can be pursued through modern statistical mechanics modeling. Here we introduce a variational maximum entropy-based algorithm to evaluate the entropy in a minimal ecosystem on a lattice in which two species struggle for survival. The method quantitatively reproduces the scale-free law of the prey shoals size, where the simpler mean-field approach fails: the direct near neighbor correlations are found to be the fundamental
more » ... ient describing the system self-organized behavior. Furthermore, entropy allows the measurement of structural ordering, that is found to be a key ingredient in characterizing two different coexistence behaviors, one where predators form localized patches in a sea of preys and another where species display more complex patterns. The general nature of the introduced method paves the way for its application in many other systems of interest.
arXiv:1803.11524v1 fatcat:nfvmudvfrvf3hheyakvq4rot3a

Genome heterogeneity drives the evolution of species

Mattia Miotto, Lorenzo Monacelli
2020 Physical Review Research  
Most of the DNA that composes a complex organism is noncoding and defined as junk. Even the coding part is composed of genes that affect the phenotype differently. Therefore a random mutation has an effect on the specimen fitness that strongly depends on the DNA region where it occurs. Understanding how this heterogeneous composition influences the fitness evolution of individuals is hampered by the complexity of the problem and a clear picture is missing. Here we study a minimal model for the
more » ... volution of an ecosystem where two antagonist species struggle for survival on a lattice. Each specimen has a unique toy genome that codes for its phenotype. The gene pool of populations changes in time due to the effect of random mutations on genes (entropic force) and of interactions with the environment and between individuals (natural selection). We prove that the relevance of each gene in the manifestation of the phenotype is a key feature for evolution. In the presence of a uniform gene relevance, a mutational meltdown is observed. Natural selection acts to quench the ecosystem in a nonequilibrium state that slowly drifts, decreasing the fitness and leading to the extinction of the species. Conversely, if a specimen is provided with a heterogeneous gene relevance, natural selection wins against entropic forces and the species evolves, increasing its fitness. We finally show that heterogeneity together with spatial correlations are responsible for spontaneous sympatric speciation.
doi:10.1103/physrevresearch.2.043026 fatcat:lqteppxmvbez3nspbb23osfnqu

Asymmetric Binomial Statistics Explains Organelle Partitioning Variance in Cancer Cell Proliferation [article]

Giovanna Peruzzi, Mattia Miotto, Roberta Maggio, Giancarlo Ruocco, Giorgio Gosti
2021 bioRxiv   pre-print
Miotto, M. & Monacelli, L. Genome heterogeneity drives the evolution of species. Phys. Rev. Research 2, 043026 (2020). 10. Elowitz, M. B. Stochastic gene expression in a single cell.  ... 
doi:10.1101/2021.01.21.427596 fatcat:k7ck452vzrcqtjmoqtyrl7g3ra

Molecular mechanisms behind anti SARS-CoV-2 action of lactoferrin [article]

Mattia Miotto, Lorenzo Di Rienzo, Leonardo Bò, Alberto Boffi, Giancarlo Ruocco, Edoardo Milanetti
2020 arXiv   pre-print
Despite the huge effort to contain the infection, the novel SARS-CoV-2 coronavirus has rapidly become pandemics, mainly due to its extremely high human-to-human transmission capability, and a surprisingly high viral charge of symptom-less people. While the seek of a vaccine is still ongoing, promising results have been obtained with antiviral compounds. In particular, lactoferrin is found to have beneficial effects both in preventing and soothing the infection. Here, we explore the possible
more » ... cular mechanisms with which lactoferrin interferes with SARS-CoV-2 cell invasion, preventing attachment and/or entry of the virus. To this aim, we search for possible interactions lactoferrin may have with virus structural proteins and host receptors. Representing the molecular iso-electron surface of proteins in terms of 2D-Zernike descriptors, we (i) identified putative regions on the lactoferrin surface able to bind sialic acid receptors on the host cell membrane, sheltering the cell from the virus attachment; (ii) showed that no significant shape complementarity is present between lactoferrin and the ACE2 receptor, while (iii) two high complementarity regions are found on the N- and C-terminal domains of the SARS-CoV-2 spike protein, hinting at a possible competition between lactoferrin and ACE2 for the binding to the spike protein.
arXiv:2007.07341v1 fatcat:b2rl6sabgbbntdskue2zq7no6m

Competing endogenous RNA crosstalk at system level

Mattia Miotto, Enzo Marinari, Andrea De Martino, Erik Aurell
2019 PLoS Computational Biology  
microRNAs (miRNAs) regulate gene expression at post-transcriptional level by repressing target RNA molecules. Competition to bind miRNAs tends in turn to correlate their targets, establishing effective RNA-RNA interactions that can influence expression levels, buffer fluctuations and promote signal propagation. Such a potential has been characterized mathematically for small motifs both at steady state and away from stationarity. Experimental evidence, on the other hand, suggests that competing
more » ... endogenous RNA (ceRNA) crosstalk is rather weak. Extended miRNA-RNA networks could however favour the integration of many crosstalk interactions, leading to significant large-scale effects in spite of the weakness of individual links. To clarify the extent to which crosstalk is sustained by the miRNA interactome, we have studied its emergent systemic features in silico in large-scale miRNA-RNA network reconstructions. We show that, although generically weak, system-level crosstalk patterns (i) are enhanced by transcriptional heterogeneities, (ii) can achieve high-intensity even for RNAs that are not co-regulated, (iii) are robust to variability in transcription rates, and (iv) are significantly non-local, i.e. correlate weakly with miRNA-RNA interaction parameters. Furthermore, RNA levels are generically more stable when crosstalk is strongest. As some of these features appear to be encoded in the network's topology, crosstalk may functionally be favoured by natural selection. These results suggest that, besides their repressive role, miRNAs mediate a weak but resilient and context-independent network of cross-regulatory interactions that interconnect the transcriptome, stabilize expression levels and support system-level responses.
doi:10.1371/journal.pcbi.1007474 pmid:31675359 pmcid:PMC6853376 fatcat:3kqgrmifing5zhijqymakrdg6u

New algorithm to determine a minimal representation of the molecular surface [article]

Greta Grassmann, Mattia Miotto, Lorenzo Di Rienzo, Giorgio Gosti, Giancarlo Ruocco, Edoardo Milanetti
2021 arXiv   pre-print
Most proteins perform their biological function by interacting with one or more molecular partners. In this respect, characterizing the features of the molecular surface, especially in the portions where the interaction takes place, turned out to be a crucial step in the investigation of the mechanisms of recognition and binding between molecules. Predictive methods often rely on extensive samplings of molecular patches with the aim to identify hot spots on the surface. In this framework,
more » ... is of large proteins and/or many molecular dynamics frames is often unfeasible due to the high computational cost. Thus, finding optimal ways to reduce the number of points to be sampled maintaining the biological information carried by the molecular surface is pivotal. Here, we present a new theoretical and computational algorithm with the aim of determining a subset of surface points, appropriately selected in space, in order to maximize the information of the overall shape of the molecule by minimizing the number of total points. We test our procedure by looking at the local shape of the surface through a recently developed method based on the formalism of Zernike polynomials in two dimensions, which is able to characterize the local shape properties of portions of molecular surfaces. The results of this method show that a remarkably higher ability of this algorithm to reproduce the information of the complete molecular surface compared to uniform random sampling.
arXiv:2107.07954v1 fatcat:uzzunfwndvedbhmm7wmsvp2vdi

In-Silico evidence for two receptors based strategy of SARS-CoV-2 [article]

Edoardo Milanetti, Mattia Miotto, Lorenzo Di Rienzo, Michele Monti, Giorgio Gosti, Giancarlo Ruocco
2020 bioRxiv   pre-print
We propose a novel numerical method able to determine efficiently and effectively the relationship of complementarity between portions of proteins surfaces. This innovative and general procedure, based on the representation of the molecular iso-electron density surface in terms of 2D Zernike polynomials, allows the rapid and quantitative assessment of the geometrical shape complementarity between interacting proteins, that was unfeasible with previous methods. We first tested the method with a
more » ... arge dataset of known protein complexes obtaining an overall area under the ROC curve of 0.69 in the blind recognition of binding sites and then applied it to investigate the features of the interaction between the Spike protein of SARS-Cov-2 and human cellular receptors. Our results indicate that SARS-CoV-2 uses a dual strategy: its spike protein could also interact with sialic acid receptors of the cells in the upper airways, in addition to the known interaction with Angiotensin-converting enzyme 2.
doi:10.1101/2020.03.24.006197 fatcat:gxdoejyxxbbc3ovglb5f2iqxmq

Thermometer: a webserver to predict protein thermal stability

Mattia Miotto, Alexandros Armaos, Lorenzo Di Rienzo, Giancarlo Ruocco, Edoardo Milanetti, Gian Gaetano Tartaglia, Alfonso Valencia
2022 Bioinformatics  
.; Miotto et al.) .  ...  We obtained 15 additional protein structures to be added to the dataset proposed in Miotto et al., 2018.  ... 
doi:10.1093/bioinformatics/btab868 pmid:35020787 pmcid:PMC8963285 fatcat:fj2pu3nmpvh5lf4dcrdka662fe

Does blood type affect the COVID-19 infection pattern?

Mattia Miotto, Lorenzo Di Rienzo, Giorgio Gosti, Edoardo Milanetti, Giancarlo Ruocco, Jeffrey Shaman
2021 PLoS ONE  
Visualization: Mattia Miotto, Giorgio Gosti. Writing -original draft: Mattia Miotto, Lorenzo Di Rienzo, Giorgio Gosti, Edoardo Milanetti, Giancarlo Ruocco.  ...  Writing -review & editing: Mattia Miotto, Lorenzo Di Rienzo, Giorgio Gosti, Edoardo Milanetti, Giancarlo Ruocco.  ... 
doi:10.1371/journal.pone.0251535 pmid:33984040 fatcat:a7nzrp64yfdavdh44eah34pppa

Investigating the side-chain structural organization behind the stability of protein folding and binding [article]

Fausta Desantis, Mattia Miotto, Lorenzo Di Rienzo, Edoardo Milanetti, Giancarlo Ruocco
2021 arXiv   pre-print
What are the molecular mechanisms that dictate protein-protein binding stability and whether those are related to the ones behind protein fold stability are still largely open questions. Indeed, despite many past efforts, we still lack definitive models to account for experimental quantities like protein melting temperature or complex binding affinity. Here, we investigate and compare chemical and physical features on a dataset of protein with known melting temperature as well as a large
more » ... of protein-protein complexes with reliable experimental binding affinity. In particular, we probed the aminoacid composition and the organization of the network of intramolecular and intermolecular interaction energies among residues. We found that hydrophobic residues present on the protein surfaces are preferentially located in the binding regions, while charged residues behave oppositely. In addition, the abundance of polar amino acid like Serine and Proline correlates with the binding affinity of the complexes. Analysing the interaction energies we found that distant Coulombic interactions are responsible for thermal stability while the total inter-molecular van der Waals energy correlates with protein-protein binding affinity.
arXiv:2107.08099v1 fatcat:y3233a47pbgkrjvsr6uoe47snu

Does blood type affect the COVID-19 infection pattern? [article]

Mattia Miotto, Lorenzo Di Rienzo, Giorgio Gosti, Edoardo Milanetti, Giancarlo Ruocco
2020 arXiv   pre-print
Among the many aspects that characterize the COVID-19 pandemic, two seem particularly challenging to understand: (i) the great geographical differences in the degree of virus contagiousness and lethality which were found in the different phases of the epidemic progression, and (ii) the potential role of the infected people's blood type in both the virus infectivity and the progression of the disease. A recent hypothesis could shed some light on both aspects. Specifically, it has been proposed
more » ... at in the subject-to-subject transfer SARS-CoV-2 conserves on its capsid the erythrocytes' antigens of the source subject. Thus these conserved antigens can potentially cause an immune reaction in a receiving subject that has previously acquired specific antibodies for the source subject antigens. This hypothesis implies a blood type-dependent infection rate. The strong geographical dependence of the blood type distribution could be, therefore, one of the factors at the origin of the observed heterogeneity in the epidemics spread. Here, we present an epidemiological deterministic model where the infection rules based on blood types are taken into account and compare our model outcomes with the exiting worldwide infection progression data. We found an overall good agreement, which strengthens the hypothesis that blood types do play a role in the COVID-19 infection.
arXiv:2007.06296v2 fatcat:2vprokijizaedjgpcqm2sf47xy

Insights on protein thermal stability: a graph representation of molecular interactions [article]

Mattia Miotto, Pier Paolo Olimpieri, Lorenzo Di Rienzo, Francesco Ambrosetti, Pietro Corsi, Rosalba Lepore, Gian Gaetano Tartaglia, Edoardo Milanetti
2018 biorxiv/medrxiv   pre-print
Understanding the molecular mechanisms of protein thermal stability is an important challenge in modern biology. Indeed, knowing the temperature at which proteins are stable has important theoretical implications, that are intimately linked with properties of the native fold, and a wide range of potential applications from drug design to the optimization of enzyme activity. Here, we present a novel graph-theoretical framework to assess thermal stability based on the protein structure without
more » ... a priori information. We describe proteins as energy-weighted inter- action networks and compare them with ensembles of interaction networks. We investigated how evolution shapes the position of specific interactions within the 3D native structure. We present a parameter-free network descriptor that permits to distinguish thermostable and mesostable proteins with an accuracy of 76% and Area Under the Roc Curve of 78%.
doi:10.1101/354266 fatcat:ag6xyow36zc57lwy533xauhqwi

Molecular Mechanisms Behind Anti SARS-CoV-2 Action of Lactoferrin

Mattia Miotto, Lorenzo Di Rienzo, Leonardo Bò, Alberto Boffi, Giancarlo Ruocco, Edoardo Milanetti
2021 Frontiers in Molecular Biosciences  
Frontiers in Molecular Biosciences | www.frontiersin.org February 2021 | Volume 8 | Article 607443 Miotto et al.Anti SARS-CoV-2 Action of Lactoferrin  ...  surface of cellular constituents, like membrane proteins Varki (2016) and are involved in many cell functions like support, signaling, protein folding, and protection Bishop and Gagneux (2007) and Miotto  ... 
doi:10.3389/fmolb.2021.607443 pmid:33659275 pmcid:PMC7917183 fatcat:yd4tiyh36jh2hhxqir2yjxznem
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