Viruses are the most abundant biological entities on Earth and play central roles in shaping microbiomes and influencing ecosystem functions. Yet, most viral genes remain uncharacterized, comprising what is commonly referred to as "viral dark matter." Metagenomic studies across diverse environments consistently show that 40-90% of viral genes lack known homologs or annotated functions. This persistent knowledge gap limits our ability to interpret viral sequence data, understand virus-host interactions, and assess the ecological or applied significance of viral genes. Among the most intriguing components of viral dark matter are auxiliary viral genes (AVGs), including auxiliary metabolic genes (AMGs), regulatory genes (AReGs), and host physiology-modifying genes (APGs), which may alter host function during infection and contribute to microbial metabolism, stress tolerance, or resistance. In this review, we explore recent advances in the discovery and functional characterization of viral dark matter. We highlight representative examples of novel viral proteins across diverse ecosystems including human microbiomes, soil, oceans, and extreme environments, and discuss what is known, and
Infectious disease dynamics operate across multiple biological scales, with within-host viral dynamics being a key driver of between-host transmission. However, while models that explicitly link these scales exist, none have been developed with statistical inference as a primary goal. In this paper we propose a multiscale model that jointly captures heterogeneous individual-level viral load trajectories and stochastic household transmission, and develop efficient inference methods to fit it to data. Since full joint inference is computationally difficult, we employ a cut approach that passes information from the within-host to the between-host model but not vice versa. This enables the data on viral loads to inform the transmission parameters such as the infection times and symptom onset thresholds. We evaluate the framework on simulated household outbreak data, assessing parameter recovery, computational efficiency, and the effect of viral load sampling frequency on inference quality. Parameter recovery is unbiased when the sampling frequency of the viral loads is high enough. When sampling is sparse, some bias is introduced, but incorporating external viral load data can mitigate
Protein language models are trained on highly imbalanced datasets, raising the question of how they represent underrepresented biological sequences. Using viral proteins as a case study across ESM model families, we identify a dominant nativeness axis in embedding space, aligned with masked reconstruction perplexity, that orders sequences from well-modeled cellular proteins through viral proteins to shuffled and random sequences. Scaling contracts this axis unevenly across viral families. Despite this, protein language model embeddings retain viral-specific signal: viral proteins remain linearly separable beyond zero-shot perplexity and shallow sequence features. Together, these results suggest that pLM representations are structured by a general notion of nativeness while preserving information specific to distinct biological groups.
Motivation: Viruses represent the most abundant biological entities on the planet and play vital roles in diverse ecosystems. Cataloging viruses across various environments is essential for understanding their properties and functions. Metagenomic sequencing has emerged as the most comprehensive method for virus discovery, enabling the sequencing of all genetic materials, including viruses, from host or environmental samples. However, distinguishing viral sequences from the vast background of cellular organism-derived reads in metagenomic data remains a significant challenge. While several learning-based tools, such as VirSorter2 and geNomad, have shown promise in identifying viral contigs, they often experience varying degrees of false positive rates due to noise in sequencing and assembly, shared genes between viruses and their hosts, and the formation of proviruses within host genomes. This highlights the urgent need for an accurate and efficient method to evaluate the quality of viral contigs. Results: To address these challenges, we introduce ViralQC, a tool designed to assess the quality of reported viral contigs or bins. ViralQC identifies contamination regions within putati
This study examines Facebook and YouTube content from over a thousand news outlets in four European languages from 2018 to 2023, using a Bayesian structural time-series model to evaluate the impact of viral posts. Our results show that most viral events do not significantly increase engagement and rarely lead to sustained growth. The virality effect usually depends on the engagement trend preceding the viral post, typically reversing it. When news emerges unexpectedly, viral events enhances users' engagement, reactivating the collective response process. In contrast, when virality manifests after a sustained growth phase, it represents the final burst of that growth process, followed by a decline in attention. Moreover, quick viral effects fade faster, while slower processes lead to more persistent growth. These findings highlight the transient effect of viral events and underscore the importance of consistent, steady attention-building strategies to establish a solid connection with the user base rather than relying on sudden visibility spikes.
For over a century, immunology has masterfully discovered and dissected the components of our immune system, yet its collective behavior remains fundamentally unpredictable. In this perspective, we argue that building on the learnings of reductionist biology and systems immunology, the field is poised for a third revolution. This new era will be driven by the convergence of purpose-built, large-scale causal experiments and predictive, generalizable AI models. Here, we propose the Predictive Immunology Loop as the unifying engine to harness this convergence. This closed loop iteratively uses AI to design maximally informative experiments and, in turn, leverages the resulting data to improve dynamic, in silico models of the human immune system across biological scales, culminating in a Virtual Immune System. This engine provides a natural roadmap for addressing immunology's grand challenges, from decoding molecular recognition to engineering tissue ecosystems. It also offers a framework to transform immunology from a descriptive discipline into one capable of forecasting and, ultimately, engineering human health.
Classical computational methods, such as molecular dynamics and Monte Carlo simulations, have long been the standard for modeling viral structure and function. However, these approaches may overlook crucial quantum phenomena that operate at the nanoscale, particularly within the highly-compacted genetic material of the viral capsid. The confined, high-density environment of genetic material within the capsid strongly suggests that quantum confinement effects play a significant, yet unexplored, role in viral processes. This study introduces a novel quantum approach using Supersymmetric Quantum Mechanics (SQM) to investigate the quantum confinement effects on viruses. In this paper, the viral capsid environment is modeled using the Pariacoto virus, a model system well-suited for this analysis due to its specific structural properties. The findings reveal that quantum effects are not merely marginal but essential for understanding key processes inside the capsid, providing new insights beyond the scope of classical physics.
There is growing recognition in both the experimental and modelling literature of the importance of spatial structure to the dynamics of viral infections in tissues. Aided by the evolution of computing power and motivated by recent biological insights, there has been an explosion of new, spatially-explicit models for within-host viral dynamics in recent years. This development has only been accelerated in the wake of the COVID-19 pandemic. Spatially-structured models offer improved biological realism and can account for dynamics which cannot be well-described by conventional, mean-field approaches. However, despite their growing popularity, spatially-structured models of viral dynamics are underused in biological applications. One major obstacle to the wider application of such models is the huge variety in approaches taken, with little consensus as to which features should be included and how they should be implemented for a given biological context. Previous reviews of the field have focused on specific modelling frameworks or on models for particular viral species. Here, we instead apply a scoping review approach to the literature of spatially-structured viral dynamics models as
The seasonal human influenza virus undergoes rapid evolution, leading to significant changes in circulating viral strains from year to year. These changes are typically driven by adaptive mutations, particularly in the antigenic epitopes, the regions of the viral surface protein haemagglutinin targeted by human antibodies. Here we describe a consistent set of methods for data-driven predictive analysis of viral evolution. Our pipeline integrates four types of data: (1) sequence data of viral isolates collected on a worldwide scale, (2) epidemiological data on incidences, (3) antigenic characterization of circulating viruses, and (4) intrinsic viral phenotypes. From the combined analysis of these data, we obtain estimates of relative fitness for circulating strains and predictions of clade frequencies for periods of up to one year. Furthermore, we obtain comparative estimates of protection against future viral populations for candidate vaccine strains, providing a basis for pre-emptive vaccine strain selection. Continuously updated predictions obtained from the prediction pipeline for influenza and SARS-CoV-2 are available on the website https://previr.app.
Social media posts may go viral and reach large numbers of people within a short period of time. Such posts may threaten the public dialogue if they contain misleading content, making their early detection highly crucial. Previous works proposed their own metrics to annotate if a tweet is viral or not in order to automatically detect them later. However, such metrics may not accurately represent viral tweets or may introduce too many false positives. In this work, we use the ground truth data provided by Twitter's "Viral Tweets" topic to review the current metrics and also propose our own metric. We find that a tweet is more likely to be classified as viral by Twitter if the ratio of retweets to its author's followers exceeds some threshold. We found this threshold to be 2.16 in our experiments. This rule results in less false positives although it favors smaller accounts. We also propose a transformers-based model to early detect viral tweets which reports an F1 score of 0.79. The code and the tweet ids are publicly available at: https://github.com/tugrulz/ViralTweets
This paper explores the nature and spread of viral WhatsApp content among everyday users in three diverse countries: India, Indonesia, and Colombia. By analyzing hundreds of viral messages collected with participants' consent from private WhatsApp groups, we provide one of the first cross-cultural categorizations of viral content on WhatsApp. Despite the differences in cultural and geographic settings, our findings reveal striking similarities in the types of groups users engage with and the viral content they receive, particularly in the prevalence of misinformation. Our comparative analysis shows that viral content often includes political and religious narratives, with misinformation frequently recirculated despite prior debunking by fact-checking organizations. These parallels suggest that closed messaging platforms like WhatsApp facilitate similar patterns of information dissemination across different cultural contexts. This work contributes to the broader understanding of global digital communication ecosystems and provides a foundation for future research on information flow and moderation strategies in private messaging platforms.
In this article, we present two novel variants of the contact process. In the first variant individuals carry a viral load. An individual with viral load zero is classified as healthy and otherwise infected. If an individual becomes infected it begins with a viral load of one, which then evolves according to a Birth-Death process. In this model, viral load indicates severity of the infection such that individuals with a higher load can be more infectious. Moreover, the recovery times of individual is not necessarily exponentially distributed and can even be chosen to follow a power-law distribution. In the second variant individuals are permanently infected albeit in two states: actively infected or dormant. The dynamics of these individual states are again governed by a Birth-Death process. Dormant infections do not interact with neighbouring individuals but may reactivate spontaneously. Active infections reactivate dormant neighbours at a constant rate and may become dormant themselves. We present for both variants a Poisson construction. For the first model, we study the phase transition of survival and discuss existence of a non-trivial upper invariant law. Additionally, we der
A key barrier to the real-world deployment of humanoid robots is the lack of autonomous loco-manipulation skills. We introduce VIRAL, a visual sim-to-real framework that learns humanoid loco-manipulation entirely in simulation and deploys it zero-shot to real hardware. VIRAL follows a teacher-student design: a privileged RL teacher, operating on full state, learns long-horizon loco-manipulation using a delta action space and reference state initialization. A vision-based student policy is then distilled from the teacher via large-scale simulation with tiled rendering, trained with a mixture of online DAgger and behavior cloning. We find that compute scale is critical: scaling simulation to tens of GPUs (up to 64) makes both teacher and student training reliable, while low-compute regimes often fail. To bridge the sim-to-real gap, VIRAL combines large-scale visual domain randomization over lighting, materials, camera parameters, image quality, and sensor delays--with real-to-sim alignment of the dexterous hands and cameras. Deployed on a Unitree G1 humanoid, the resulting RGB-based policy performs continuous loco-manipulation for up to 54 cycles, generalizing to diverse spatial and
Virality of online content on social networking websites is an important but esoteric phenomenon often studied in fields like marketing, psychology and data mining. In this paper we study viral images from a computer vision perspective. We introduce three new image datasets from Reddit, and define a virality score using Reddit metadata. We train classifiers with state-of-the-art image features to predict virality of individual images, relative virality in pairs of images, and the dominant topic of a viral image. We also compare machine performance to human performance on these tasks. We find that computers perform poorly with low level features, and high level information is critical for predicting virality. We encode semantic information through relative attributes. We identify the 5 key visual attributes that correlate with virality. We create an attribute-based characterization of images that can predict relative virality with 68.10% accuracy (SVM+Deep Relative Attributes) -- better than humans at 60.12%. Finally, we study how human prediction of image virality varies with different `contexts' in which the images are viewed, such as the influence of neighbouring images, images r
Viruses and their hosts are involved in an 'arms race' where they continually evolve mechanisms to overcome each other. It has long been proposed that intrinsic disorder provides a substrate for the evolution of viral hijack functions and that short linear motifs (SLiMs) are important players in this process. Here, we review evidence in support of this tenet from two model systems: the papillomavirus E7 protein and the adenovirus E1A protein. Phylogenetic reconstructions reveal that SLiMs appear and disappear multiple times across evolution, providing evidence of convergent evolution within individual viral phylogenies. Multiple functionally related SLiMs show strong co-evolution signals that persist across long distances in the primary sequence and occur in unrelated viral proteins. Moreover, changes in SLiMs are associated with changes in phenotypic traits such as host range and tropism. Tracking viral evolutionary events reveals that host switch events are associated with the loss of several SLiMs, suggesting that SLiMs are under functional selection and that changes in SLiMs support viral adaptation. Fine-tuning of viral SLiM sequences can improve affinity, allowing them to out
The COVID-19 pandemic has given rise to numerous articles from different scientific fields (epidemiology, virology, immunology, airflow physics...) without any effort to link these different insights. In this review, we aim to establish relationships between epidemiological data and the characteristics of the virus strain responsible for the epidemic wave concerned. We have carried out this study on the Wuhan, Alpha, Delta and Omicron strains allowing us to illustrate the evolution of the relationships we have highlighted according to these different viral strains. We addressed the following questions: 1) How can the mean infectious dose (one quantum, by definition in epidemiology) be measured and expressed as an amount of viral RNA molecules (in genome units, GU) or as a number of replicative viral particles (in plaque-forming units, PFU)? 2) How many infectious quanta are exhaled by an infected person per unit of time? 3) How many infectious quanta are exhaled, on average, integrated over the whole contagious period? 4) How do these quantities relate to the epidemic reproduction rate R as measured in epidemiology, and to the viral load, as measured by molecular biological methods
In this paper we study intra-host viral adaptation by antigenic cooperation - a mechanism of immune escape that serves as an alternative to the standard mechanism of escape by continuous genomic diversification and allows to explain a number of experimental observations associated with the establishment of chronic infections by highly mutable viruses. Within this mechanism, the topology of a cross-immunoreactivity network forces intra-host viral variants to specialize for complementary roles and adapt to host's immune response as a quasi-social ecosystem. Here we study dynamical changes in immune adaptation caused by evolutionary and epidemiological events. First, we show that the emergence of a viral variant with altered antigenic features may result in a rapid re-arrangement of the viral ecosystem and a change in the roles played by existing viral variants. In particular, it may push the population under immune escape by genomic diversification towards the stable state of adaptation by antigenic cooperation. Next, we study the effect of a viral transmission between two chronically infected hosts, which results in merging of two intra-host viral populations in the state of stable
We present a methodology providing a one-directional link from within-host individual heterogeneity to population-level disease transmission dynamics. The methodology works in several steps. A within-host model is investigated numerically to determine pathogen and immunological parameters leading to the largest variation of model responses. These key parameters are used to generate a synthetic population of individuals whose temporal immunological response profiles are recorded. These responses are ranked in terms of the severity of experienced outcomes, from mild infections to death, as a function of time since infection. This is used to parametrise an age-of-infection structured epidemiological model to study the transmission dynamics of the disease at the population level. The approach is illustrated using a within-host model describing SARS-CoV-2 infection and an SIR population-level model.
Increasingly, experimentalists and modellers alike have come to recognise the important role of spatial structure in infection dynamics. Almost invariably, spatial computational models of viral infections - as with in vitro experimental systems - represent the tissue as wide and flat, which is often assumed to be representative of entire affected tissue within the host. However, this assumption fails to take into account the distinctive geometry of the respiratory tract in the context of viral infections. The respiratory tract is characterised by a tubular, branching structure, and moreover is spatially heterogeneous: deeper regions of the lung are composed of far narrower airways and are associated with more severe infection. Here, we extend a typical multicellular model of viral dynamics to account for two essential features of the geometry of the respiratory tract: the tubular structure of airways, and the branching process between airway generations. We show that, with this more realistic tissue geometry, the dynamics of infection are substantially changed compared to standard computational and experimental approaches, and that the resulting model is equipped to tackle importan
The viral load is known to be a chief predictor of the risk of transmission of infectious diseases. In this work, we investigate the role of the individuals' viral load in the disease transmission by proposing a new susceptible-infectious-recovered epidemic model for the densities and mean viral loads of each compartment. To this aim, we formally derive the compartmental model from an appropriate microscopic one. Firstly, we consider a multi-agent system in which individuals are identified by the epidemiological compartment to which they belong and by their viral load. Microscopic rules describe both the switch of compartment and the evolution of the viral load. In particular, in the binary interactions between susceptible and infectious individuals, the probability for the susceptible individual to get infected depends on the viral load of the infectious individual. Then, we implement the prescribed microscopic dynamics in appropriate kinetic equations, from which the macroscopic equations for the densities and viral load momentum of the compartments are eventually derived. In the macroscopic model, the rate of disease transmission turns out to be a function of the mean viral load