Stefan Wuchty

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Verified

Stefan verified their affiliation via an institutional email.

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• PhD
• Professor at University of Miami

Conspiracy theories attempt to explain events and circumstances by attributing them to the supposed secret actions of powerful, malevolent groups. Due to their associations with potentially harmful non-normative behaviors at both the individual and collective levels, researchers have expressed particular concern over conspiracy theories that malign...

Conspiracy theories attempt to explain social phenomena by attributing them to the supposed secret actions of powerful, malevolent groups. Due to their associations with potentially harmful nonnormative behaviours at both the individual and collective levels, researchers have expressed particular concern over conspiracy theories that malign science...

Tandem repeats are a highly polymorphic class of genomic variation that play causal roles in rare diseases but are notoriously difficult to sequence using short-read techniques. Most previous studies profiling tandem repeats genome-wide have reduced the description of each locus to the singular value of the length of the entire repetitive locus. He...

Repeated antigen exposure leads to T-cell exhaustion, a transcriptionally and epigenetically distinct cellular state marked by loss of effector functions (e.g., cytotoxicity, cytokine production/release), up-regulation of inhibitory receptors (e.g., PD-1), and reduced proliferative capacity. Molecular pathways underlying T-cell exhaustion have been...

Hematologic malignancies cause significant morbidity/mortality in both children and young adults (CYAs) as well as older adults (OAs). Yet their biological underpinnings remain inadequately understood. Here, we analyzed clinical and genomic disparities between CYAs and OAs in various hematologic malignancies. We found substantial differences in cli...

A moral panic animated by conspiracy theories alleging ritual sex abuse swept through the United States in the 1980s. During that “Satanic Panic,” as it came to be known, people expressed fears of social change regarding gender and sexuality. Beginning in 2022, conservative politicians, pundits, and pastors in the United States levied similar accus...

Despite hundreds of studies examining belief in conspiracy theories, it is still unclear who—demographically—is most likely to believe such theories. To remedy this knowledge gap, we examine survey data containing various operationalizations of conspiracism across diverse sociopolitical contexts. Study 1 employs a 2021 U.S. survey (n = 2021) to exa...

The molecular pathology of stress-related disorders remains elusive. Our brain multiregion, multiomic study of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD) included the central nucleus of the amygdala, hippocampal dentate gyrus, and medial prefrontal cortex (mPFC). Genes and exons within the mPFC carried most disease sig...

A recent U.S. survey explored how media exposure impacts people’s beliefs in COVID-19 conspiracy theories and vaccine behavior. This study found that individuals frequently exposed to fringe social media tend to hold stronger beliefs in COVID-19 conspiracy theories and exhibit vaccine hesitancy. They also tend to possess dark personality traits, mi...

A dysfunction of human host genes and proteins in coronavirus infectious disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key factor impacting clinical symptoms and outcomes. Yet, a detailed understanding of human host immune responses is still incomplete. Here, we applied RNA sequencing to 94 samp...

The “White Replacement” conspiracy theory, that governments and corporations are “replacing” white people, is linked to several mass shootings. Given its recent ubiquity in elite rhetoric, concerns have arisen about the popularity of this conspiracy theory among the United States mass public. Further, political scientists have noted a need to under...

We often assume that annotation tasks, such as annotating for the presence of conspiracy theories , can be annotated with hard labels, without definitions or guidelines. Our annotation experiments, comparing students and experts, show that there is little agreement on basic annotations even among experts. For this reason, we conclude that we need t...

Expansions of tandem repeats (TRs) cause approximately 60 monogenic diseases. We expect that the discovery of additional pathogenic repeat expansions will narrow the diagnostic gap in many diseases. A growing number of TR expansions are being identified, and interpreting them is a challenge. We present RExPRT (Repeat EXpansion Pathogenicity pRedict...

The identification of human-herpesvirus protein–protein interactions (PPIs) is an essential and important entry point to understand the mechanisms of viral infection, especially in malignant tumor patients with common herpesvirus infection. While natural language processing (NLP)-based embedding techniques have emerged as powerful approaches, the a...

Minor intron-containing genes (MIGs) account for less than 2% of all human protein coding genes and are uniquely dependent on the minor spliceosome for proper excision. Despite their low numbers, we surprisingly found significant enrichment of MIG-encoded proteins (MIG-Ps) in protein-protein interactomes and host factors of positive sense RNA virus...

Some people share misinformation accidentally, but others do so knowingly. To fully understand the spread of misinformation online, it is important to analyze those who purposely share it. Using a 2022 U.S. survey, we found that 14 percent of respondents reported knowingly sharing misinformation, and that these respondents were more likely to also...

The evolutionarily conserved minor spliceosome (MiS) is required for protein expression of ∼714 minor intron-containing genes (MIGs) crucial for cell-cycle regulation, DNA repair, and MAP-kinase signaling. We explored the role of MIGs and MiS in cancer, taking prostate cancer (PCa) as an exemplar. Both androgen receptor signaling and elevated level...

While RNA secondary structures are critical to regulate alternative splicing of long-range pre-mRNA, the factors that modulate RNA structure and interfere with the recognition of the splice sites are largely unknown. Previously, we identified a small, non-coding microRNA that sufficiently affects stable stem structure formation of Nmnat pre-mRNA to...

While a robust literature on the psychology of conspiracy theories has identified dozens of characteristics correlated with conspiracy theory beliefs, much less attention has been paid to understanding the generalized predisposition towards interpreting events and circumstances as the product of supposed conspiracies. Using a unique national survey...

Taxanes are chemotherapeutic agents that induce microtubule modifications in cancer cells, resulting in cell cycle modifications and tumor remission. Here we show that paclitaxel, a widely used taxane, also induces microtubule modifications in healthy epidermal keratinocytes leading to chemotherapy-induced peripheral neuropathy (CIPN). Paclitaxel a...

While RNA secondary structures are critical to regulate alternative splicing of long-range pre-mRNA, the factors that modulate RNA structure and interfere with the recognition of the splice sites are largely unknown. Previously, we identified a small, non-coding microRNA that sufficiently affects stable stem structure formation of Nmnat pre-mRNA to...

Interdisciplinary research has emerged as a hotbed for innovation and discoveries. The increasing dominance of grant-supported research, combined with growing interest in funding interdisciplinary work, raises fundamental questions on the role of interdisciplinary grants in supporting high-impact interdisciplinary advances. Here we develop a measur...

Tandem repeats (TRs) are polymorphic sequences of DNA that are composed of repeating units of motifs ranging from 2-6 base pairs in length. Expansions of TRs are responsible for approximately 50 monogenic diseases, compared to over 4,300 disease causing genes disrupted by single nucleotide variants and small indels. It appears thus reasonable to ex...

Currently, the experimentally identified interactome of Arabidopsis (Arabidopsis thaliana) is still far from complete, suggesting that computational prediction methods can complement experimental techniques. Motivated by the prosperity and success of deep learning algorithms and natural language processing techniques, we introduce an integrative de...

A proper understanding of disease etiology will require longitudinal systems-scale reconstruction of the multitiered architecture of eukaryotic signaling. Here we combine state-of-the-art data acquisition platforms and bioinformatics tools to devise PAMAF, a workflow that simultaneously examines twelve omics modalities, i.e., protein abundance from...

While deep learning (DL)-based models have emerged as powerful approaches to predict protein–protein interactions (PPIs), the reliance on explicit similarity measures (e.g. sequence similarity and network neighborhood) to known interacting proteins makes these methods ineffective in dealing with novel proteins. The advent of AlphaFold2 presents a s...

Understanding the individual-level characteristics associated with conspiracy theory beliefs is vital to addressing and combatting those beliefs. While researchers have identified numerous psychological and political characteristics associated with conspiracy theory beliefs, the generalizability of those findings is uncertain because they are typic...

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed the world's unpreparedness to deal with the emergence of novel pathogenic viruses, pointing to the urgent need to identify targets for broad-spectrum antiviral strategies. Here, we report that proteins encoded by Minor Intron-containing Genes (MIGs) are...

The QAnon conspiracy theory has garnered increasing attention as more than 80 pro- QAnon congressional candidates vied for nominations in 2020 primary races. The QAnon movement is widely characterized as “far-right” and “growing,” but such claims rest on flimsy evidence. Using 6 public opinion polls from 2018-2020, we find that support for QAnon is...

Scholars initially envisioned digital and social media as a modern-day town hall where informed citizens and activists challenge prevailing ideologies and freely communicate and engage with others interested in changing the status quo. The value of this experience is the rise of a participatory, cooperative media ecology essential for raising the p...

The overarching goal of the current study is thus to explore how malicious actors frame conspiratorial rhetoric where certain tropes and modes of emplotment formed in tweets cultivate a polarized echo chamber provoking affective responses of susceptible individuals. This study provides evidence linking past CTs with contemporary narratives broadly...

Identifying human-virus protein-protein interactions (PPIs) is an essential step for understanding viral infection mechanisms and antiviral response of the human host. Recent advances in high-throughput experimental techniques enable the significant accumulation of human-virus PPI data, which have further fueled the development of machine learning-...

Understanding the mechanisms of tissue-specific transcriptional regulation is crucial as mis-regulation can cause a broad range of diseases. Here, we investigated transcription factors (TF) that are indispensable for the topological control of tissue specific and cell-type specific regulatory networks as a function of their binding to regulatory el...

Motivation: To complement experimental efforts, machine learning-based computational methods are playing an increasingly important role to predict human-virus protein-protein interactions (PPIs). Furthermore, transfer learning can effectively apply prior knowledge obtained from a large source dataset/task to a small target dataset/task, improving...

Posttraumatic stress disorder (PTSD) is a debilitating syndrome with substantial morbidity and mortality that occurs in the aftermath of trauma. Symptoms of major depressive disorder (MDD) are also a frequent consequence of trauma exposure. Identifying novel risk markers in the immediate aftermath of trauma is a critical step for the identification...

Contemporary political ills at the mass behavior level (e.g., outgroup aggression, conspiracy theories) are often attributed to increasing polarization and partisan tribalism. We theorize that many such problems are less the product of left-right orientations than an orthogonal “anti-establishment” dimension of opinion dominated by conspiracy, popu...

TGFβ mediated epithelial to mesenchymal transition (EMT) proceeds through hybrid "E/M" states. A deeper understanding of these states and events which regulate entry to and exit from the E/M states is needed for therapeutic exploitation. We quantified >60,000 molecules across ten time points and twelve omic layers in mammary epithelial cells. Prote...

Biomarkers that predict symptom trajectories after trauma can facilitate early detection or intervention for posttraumatic stress disorder (PTSD) and may also advance our understanding of its biology. Here, we aimed to identify trajectory-based biomarkers using blood transcriptomes collected in the immediate aftermath of trauma exposure. Participan...

To predict interactions between human and viral proteins, we combine evolutionary sequence profile features with a Siamese convolutional neural network (CNN) architecture and a multi-layer perceptron (MLP). Our architecture outperforms various feature encodings-based machine learning and state-of-the-art prediction methods. As our main contribution...

While leading to millions of people’s deaths every year the treatment of viral infectious diseases remains a huge public health challenge.Therefore, an in-depth understanding of human–virus protein–protein interactions (PPIs) as the molecular interface between a virus and its host cell is of paramount importance to obtain new insights into the path...

Human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative pathogen of the COVID-19 pandemic, exerts a massive health and socioeconomic crisis. The virus infects alveolar epithelial type 2 cells (AT2s), leading to lung injury and impaired gas exchange, but the mechanisms driving infection and pathology are unclear...

Many governments have managed to control their COVID-19 outbreak with a simple message: keep the effective '$R$ number' $R<1$ to prevent widespread contagion and flatten the curve. This raises the question whether a similar policy could control dangerous online 'infodemics' of information, misinformation and disinformation. Here we show, using mult...

The determination of signaling pathways and transcriptional networks that control various biological processes is a major challenge from both basic science and translational medicine perspectives. Because such analysis can point to critical disease driver nodes to target for therapeutic purposes, we combined data from phenotypic screening experimen...

Distrust in scientific expertise1,2,3,4,5,6,7,8,9,10,11,12,13,14 is dangerous. Opposition to vaccination with a future vaccine against SARS-CoV-2, the causal agent of COVID-19, for example, could amplify outbreaks2,3,4, as happened for measles in 20195,6. Homemade remedies7,8 and falsehoods are being shared widely on the Internet, as well as dismis...

Inputs to molecular pathways that are the backbone of cellular activity drive the cell to certain outcomes and phenotypes. Here, we investigated proteins that topologically controlled different human pathways represented as independent molecular interaction networks, suggesting that a minority of proteins control a high number of pathways and vice...

Like all organisms, aphids, plant sap-sucking insects that house a bacterial endosymbiont called Buchnera, are members of a species interaction network. Ecological interactions across such networks can result in phenotypic change in network members mediated by molecular signals, like microRNAs. Here, we interrogated small RNA data from the aphid, M...

The identification of human-virus protein-protein interactions (PPIs) is an essential and challenging research topic, potentially providing a mechanistic understanding of viral infection. Given that the experimental determination of human-virus PPIs is time-consuming and labor-intensive, computational methods are playing an important role in provid...

Axonal injury results in regenerative success or failure, depending on whether the axon lies in the peripheral or the CNS, respectively. The present study addresses whether epigenetic signatures in dorsal root ganglia discriminate between regenerative and non-regenerative axonal injury. Chromatin immunoprecipitation for the histone 3 (H3) post-tran...

We present preliminary results on the online war surrounding distrust of expertise in medical science -- specifically, the issue of vaccinations. While distrust and misinformation in politics can damage democratic elections, in the medical context it may also endanger lives through missed vaccinations and DIY cancer cures. We find that this online...

Online hate and extremist narratives have been linked to abhorrent real-world events, including a current surge in hate crimes1–6 and an alarming increase in youth suicides that result from social media vitriol⁷; inciting mass shootings such as the 2019 attack in Christchurch, stabbings and bombings8–11; recruitment of extremists12–16, including en...

Understanding endogenous regulation of stress resistance and homeostasis maintenance is critical to developing neuroprotective therapies. Nicotinamide mononucleotide adenylyltransferase (NMNAT) is a conserved essential enzyme that confers extraordinary protection and stress resistance in many neurodegenerative disease models. Drosophila Nmnat is al...

Background: Histone deacetylases (HDACs) are the proteins responsible for removing the acetyl group from lysine residues of core histones in chromosomes, a crucial component of gene regulation. Eleven known HDACs exist in humans and most other vertebrates. While the basic function of HDACs has been well characterized and new discoveries are still...

The determination of a small set of biomarkers to make a diagnostic call can be formulated as a feature subset selection (FSS) problem to find a small set of genes with high relevance for the underlying classification task and low mutual redundancy. However, repeated application of a heuristic, evolutionary FSS technique usually fails to produce co...

Understanding endogenous regulation of stress resistance and homeostasis maintenance is critical to developing neuroprotective therapies. Nicotinamide mononucleotide adenylyltransferase (NMNAT) is a conserved essential enzyme that confers extraordinary protection and stress resistance in many neurodegenerative disease models. Drosophila Nmnat is al...

Recent research increasingly shows the relevance of network based approaches for our understanding of biological systems. Analyzing human protein interaction networks, we determined collective influencers (CI), defined as network nodes that damage the integrity of the underlying networks to the utmost degree. We found that CI proteins were enriched...

Inputs to molecular pathways that are the backbone of cellular activity drive the cell to certain outcomes and phenotypes. Here, we investigated proteins that topologically controlled different human pathways represented as independent molecular interaction networks, suggesting that a minority of proteins control a high number of pathways and vice...

Inherited axonopathies represent a spectrum of disorders unified by the common pathological mechanism of length-dependent axonal degeneration. Progressive axonal degeneration can lead to both Charcot-Marie-Tooth type 2 (CMT2) and Hereditary Spastic Paraplegia (HSP) depending on the affected neurons: peripheral motor and sensory nerves or central ne...

Evolutionary computation (EC) algorithms, such as discrete and multi-objective versions of particle swarm optimization (PSO), have been applied to solve the Feature selection (FS) problem, tackling the combinatorial explosion of search spaces that are peppered with local minima. Furthermore, high-dimensional FS problems such as finding a small set...

Viruses infect their human hosts by a series of interactions between viral and host proteins, indicating that detailed knowledge of such virus-host interaction interfaces are critical for our understanding of viral infection mechanisms, disease etiology and the development of new drugs. In this review, we primarily survey human host-virus interacti...

The availability of large-scale screens of host-virus interaction interfaces enabled the topological analysis of viral protein targets of the host. In particular, host proteins that bind viral proteins are generally hubs and proteins with high betweenness centrality. Recently, other topological measures were introduced that a virus may tap to infec...

Enrichment of viral targets as a function of pathway participation. We determined the enrichment of viral targets as a function of targeted protein’s occurrence in different pathways. Randomly sampling viral target sets 10,000 times, we found that targets appeared to be involved in an increasing number of pathways, a result that held for KEGG, Reac...

Enrichment of (in-)dispensable and neutral proteins. We randomly sampled sets of (in-)dispensable and neutral proteins and determined their enrichment in bins of proteins that occur in a certain number of KEGG, Reactome and Biocarta/NCI pathways. In all cases, we observed that indispensable proteins preferably appeared in an increasing number of pa...

Proteins with high protein PageRank index are enriched with viral targets. Randomizing sets of viral targets 10,000 times we determined their enrichment in sets of the top 20% of proteins with highest PageRank index. We observed that proteins with top PageRank were significantly enriched with viral targets and vice versa (P < 0.01). Notably, such o...

Frequency distributions of proteins pathway participation. Utilizing networks that were obtained from pathways in Reactome, Kegg, and Biocarta/NCI, we observed heavy tails in the frequency distributions of the numbers of pathways that proteins occur in. (TIFF)

Importance of topological measures. We utilized all five topological measures to predict viral targets using a random forest. We found that protein PageRank had the highest impact on the classification process, a result that was independent of the underlying virus and pathway information. (TIFF)

Enrichment of viral targets in sets of hubs and bottlenecks. Defining the top 20% of most connected proteins as hubs and top 20% of proteins with highest betweenness centrality as bottleneck proteins, we determined the enrichment of viral targets in such sets. Randomly sampling viral target sets 10,000 times, we generally observed that viral target...

Network controllers are enriched with viral targets. Randomizing sets of proteins that are targeted by Hepatitis, Herpes, HIV, Influenza and other viruses 10,000 times, we observed that indispensable proteins were preferably targeted by viruses (P<10−4) while the opposite held for dispensable nodes. Such observations held irrespective of the underl...

Performance of random forest classifier, predicting viral targets. Focusing on proteins that are targeted by Hepatitis, Herpes, Influenza and other viruses, we randomly sampled non-targeted proteins of equal size 1,000 times. Furthermore, we used a random forest trained with the three most and least important features. In all cases, we found that t...

Classifier performance of different topological measures. Considering target sets of Hepatitis, Herpes, HIV, Influenza and other viruses, we randomly sampled sets of non-targeted proteins of equal size. In comparison to betweenness centrality (BC) and protein’s indispensability (C) we observed that protein PageRank index (PR), pathway participation...

Correlation between topological measures. The heatmap indicated Pearson correlation values between the distributions of degree, betweenness centrality, number of pathways a protein is involved in, protein PageRank and indispensability of a protein using different pathway information. (TIFF)

Helicobacter pylori is a common pathogen that is estimated to infect half of the human population, causing several diseases such as duodenal ulcer. Despite one of the first pathogens to be sequenced, its proteome remains poorly characterised as about one third of its proteins have no functional annotation. Here, we integrate and analyze known prote...

Bacterial cell envelope protein (CEP) complexes mediate a range of processes, including membrane assembly, antibiotic resistance and metabolic coordination. However, only limited characterization of relevant macromolecules has been reported to date. Here we present a proteomic survey of 1,347 CEPs encompassing 90% inner- and outer-membrane and peri...

Although many insects are associated with obligate bacterial endosymbionts, the mechanisms by which these host/endosymbiont associations are regulated remain mysterious. While microRNAs (miRNAs) have been recently identified as regulators of host/microbe interactions, including host/pathogen and host/facultative endosymbiont interactions, the role...

The functions of roughly a third of all proteins in Streptococcus pneumoniae , a significant human-pathogenic bacterium, are unknown. Using a yeast two-hybrid approach, we have determined more than 2,000 novel protein interactions in this organism. We augmented this network with meta-interactome data that we defined as the pool of all interactions...

The discovery, validation, and characterization of protein-based interactions from different species are crucial for translational research regarding a variety of pathogens, ranging from the malaria parasite Plasmodium falciparum to HIV-1. Here, we review recent advances in the prediction of host–pathogen protein interfaces using structural informa...

Focusing on the interactomes of H. sapiens, S. cerevisiae, and E. coli, we investigated interactions between controlling proteins. In particular, we determined critical, intermittent, and redundant proteins based on their tendency to participate in minimum dominating sets (MDSets). Independently of the organisms considered, we found that interactio...

Background Protein-protein interactions (PPIs) can offer compelling evidence for protein function, especially when viewed in the context of proteome-wide interactomes. Bacteria have been popular subjects of interactome studies: more than six different bacterial species have been the subjects of comprehensive interactome studies while several more h...

Binary protein interactions form the basic building blocks of molecular networks and dynamic assemblies that control all cellular functions of bacteria. While these protein interactions are a potential source of targets for the development of new antibiotics, few high-confidence data sets are available for the large proteomes of most pathogenic bac...

A popular stereotype is that women will play more minor roles than men as environments become more dangerous and aggressive. Our analysis of new longitudinal data sets from offline and online operational networks [for example, ISIS (Islamic State)] shows that although men dominate numerically, women emerge with superior network connectivity that ca...

Although an abundance of bacteriophages exists, little is known about interactions between their proteins and those of their bacterial hosts. Here, we experimentally determined the phage-host interactomes of the phages Dp-1 and Cp-1 and their underlying protein interaction network in the host Streptococcus pneumoniae. We compared our results to the...

Tackling the advance of online threats Online support for adversarial groups such as Islamic State (ISIS) can turn local into global threats and attract new recruits and funding. Johnson et al. analyzed data collected on ISIS-related websites involving 108,086 individual followers between 1 January 1 and 31 August 2015. They developed a statistical...

Support for extremist entities - whether from the far right, or far left - often manages to survive globally online despite significant external pressure, and may ultimately inspire violent acts by individuals having no obvious prior history of extremism. Examining longitudinal records of extremist online activity, we uncovered an ecology evolving...

The investigation of host-pathogen interaction interfaces and their constituent factors is crucial for our understanding of an organism's pathogenesis. Here, we explored the interactomes of HIV, hepatitis C virus, influenza A virus, human papillomavirus, herpes simplex virus, and vaccinia virus in a human host by analyzing the combined sets of viru...

Minimum dominating sets (MDSet) of protein interaction networks allow the control of underlying protein interaction networks through their topological placement. While essential proteins are enriched in MDSets, we hypothesize that the statistical properties of biological functions of essential genes are enhanced when we focus on essential MDSet pro...