VEuPathDB: the eukaryotic pathogen, vector and host bioinformatics resource center in 2023.

The Eukaryotic Pathogen, Vector and Host Informatics Resource (VEuPathDB, https://veupathdb.org) is a Bioinformatics Resource Center funded by the National Institutes of Health with additional funding from the Wellcome Trust. VEuPathDB supports >600 organisms that comprise invertebrate vectors, eukaryotic pathogens (protists and fungi) and relevant free-living or non-pathogenic species or hosts. Since 2004, VEuPathDB has analyzed omics data from the public domain using contemporary bioinformatic workflows, including orthology predictions via OrthoMCL, and integrated the analysis results with analysis tools, visualizations, and advanced search capabilities. The unique data mining platform coupled with >3000 pre-analyzed data sets facilitates the exploration of pertinent omics data in support of hypothesis driven research. Comparisons are easily made across data sets, data types and organisms. A Galaxy workspace offers the opportunity for the analysis of private large-scale datasets and for porting to VEuPathDB for comparisons with integrated data. The MapVEu tool provides a platform for exploration of spatially resolved data such as vector surveillance and insecticide resistance monitoring. To address the growing body of omics data and advances in laboratory techniques, VEuPathDB has added several new data types, searches and features, improved the Galaxy workspace environment, redesigned the MapVEu interface and updated the infrastructure to accommodate these changes.

VEuPathDB: the eukaryotic pathogen, vector and host bioinformatics resource center.

The Eukaryotic Pathogen, Vector and Host Informatics Resource (VEuPathDB, https://veupathdb.org) represents the 2019 merger of VectorBase with the EuPathDB projects. As a Bioinformatics Resource Center funded by the National Institutes of Health, with additional support from the Welllcome Trust, VEuPathDB supports >500 organisms comprising invertebrate vectors, eukaryotic pathogens (protists and fungi) and relevant free-living or non-pathogenic species or hosts. Designed to empower researchers with access to Omics data and bioinformatic analyses, VEuPathDB projects integrate >1700 pre-analysed datasets (and associated metadata) with advanced search capabilities, visualizations, and analysis tools in a graphic interface. Diverse data types are analysed with standardized workflows including an in-house OrthoMCL algorithm for predicting orthology. Comparisons are easily made across datasets, data types and organisms in this unique data mining platform. A new site-wide search facilitates access for both experienced and novice users. Upgraded infrastructure and workflows support numerous updates to the web interface, tools, searches and strategies, and Galaxy workspace where users can privately analyse their own data. Forthcoming upgrades include cloud-ready application architecture, expanded support for the Galaxy workspace, tools for interrogating host-pathogen interactions, and improved interactions with affiliated databases (ClinEpiDB, MicrobiomeDB) and other scientific resources, and increased interoperability with the Bacterial & Viral BRC.

Improved eukaryotic detection compatible with large-scale automated analysis of metagenomes.

BACKGROUND: Eukaryotes such as fungi and protists frequently accompany bacteria and archaea in microbial communities. Unfortunately, their presence is difficult to study with "shotgun" metagenomic sequencing since prokaryotic signals dominate in most environments. Recent methods for eukaryotic detection use eukaryote-specific marker genes, but they do not incorporate strategies to handle the presence of eukaryotes that are not represented in the reference marker gene set, and they are not compatible with web-based tools for downstream analysis. RESULTS: Here, we present CORRAL (for Clustering Of Related Reference ALignments), a tool for the identification of eukaryotes in shotgun metagenomic data based on alignments to eukaryote-specific marker genes and Markov clustering. Using a combination of simulated datasets, mock community standards, and large publicly available human microbiome studies, we demonstrate that our method is not only sensitive and accurate but is also capable of inferring the presence of eukaryotes not included in the marker gene reference, such as novel strains. Finally, we deploy CORRAL on our MicrobiomeDB.org resource, producing an atlas of eukaryotes present in various environments of the human body and linking their presence to study covariates. CONCLUSIONS: CORRAL allows eukaryotic detection to be automated and carried out at scale. Implementation of CORRAL in MicrobiomeDB.org creates a running atlas of microbial eukaryotes in metagenomic studies. Since our approach is independent of the reference used, it may be applicable to other contexts where shotgun metagenomic reads are matched against redundant but non-exhaustive databases, such as the identification of bacterial virulence genes or taxonomic classification of viral reads. Video Abstract.

From calcium imaging to graph topology.

Systems neuroscience is facing an ever-growing mountain of data. Recent advances in protein engineering and microscopy have together led to a paradigm shift in neuroscience; using fluorescence, we can now image the activity of every neuron through the whole brain of behaving animals. Even in larger organisms, the number of neurons that we can record simultaneously is increasing exponentially with time. This increase in the dimensionality of the data is being met with an explosion of computational and mathematical methods, each using disparate terminology, distinct approaches, and diverse mathematical concepts. Here we collect, organize, and explain multiple data analysis techniques that have been, or could be, applied to whole-brain imaging, using larval zebrafish as an example model. We begin with methods such as linear regression that are designed to detect relations between two variables. Next, we progress through network science and applied topological methods, which focus on the patterns of relations among many variables. Finally, we highlight the potential of generative models that could provide testable hypotheses on wiring rules and network progression through time, or disease progression. While we use examples of imaging from larval zebrafish, these approaches are suitable for any population-scale neural network modeling, and indeed, to applications beyond systems neuroscience. Computational approaches from network science and applied topology are not limited to larval zebrafish, or even to systems neuroscience, and we therefore conclude with a discussion of how such methods can be applied to diverse problems across the biological sciences.

Brain-wide visual habituation networks in wild type and fmr1 zebrafish.

Habituation is a form of learning during which animals stop responding to repetitive stimuli, and deficits in habituation are characteristic of several psychiatric disorders. Due to technical challenges, the brain-wide networks mediating habituation are poorly understood. Here we report brain-wide calcium imaging during larval zebrafish habituation to repeated visual looming stimuli. We show that different functional categories of loom-sensitive neurons are located in characteristic locations throughout the brain, and that both the functional properties of their networks and the resulting behavior can be modulated by stimulus saliency and timing. Using graph theory, we identify a visual circuit that habituates minimally, a moderately habituating midbrain population proposed to mediate the sensorimotor transformation, and downstream circuit elements responsible for higher order representations and the delivery of behavior. Zebrafish larvae carrying a mutation in the fmr1 gene have a systematic shift toward sustained premotor activity in this network, and show slower behavioral habituation.

Modeling brain, symptom, and behavior in the winds of change.

Neuropsychopharmacology addresses pressing questions in the study of three intertwined complex systems: the brain, human behavior, and symptoms of illness. The field seeks to understand the perturbations that impinge upon those systems, either driving greater health or illness. In the pursuit of this aim, investigators often perform analyses that make certain assumptions about the nature of the systems that are being perturbed. Those assumptions can be encoded in powerful computational models that serve to bridge the wide gulf between a descriptive analysis and a formal theory of a system's response. Here we review a set of three such models along a continuum of complexity, moving from a local treatment to a network treatment: one commonly applied form of the general linear model, impulse response models, and network control models. For each, we describe the model's basic form, review its use in the field, and provide a frank assessment of its relative strengths and weaknesses. The discussion naturally motivates future efforts to interlink data analysis, computational modeling, and formal theory. Our goal is to inspire practitioners to consider the assumptions implicit in their analytical approach, align those assumptions to the complexity of the systems under study, and take advantage of exciting recent advances in modeling the relations between perturbations and system function.

Hunters, busybodies and the knowledge network building associated with deprivation curiosity.

The open-ended and internally driven nature of curiosity makes characterizing the information seeking that accompanies it a daunting endeavour. We use a historico-philosophical taxonomy of information seeking coupled with a knowledge network building framework to capture styles of information-seeking in 149 participants as they explore Wikipedia for over 5 hours spanning 21 days. We create knowledge networks in which nodes represent distinct concepts and edges represent the similarity between concepts. We quantify the tightness of knowledge networks using graph theoretical indices and use a generative model of network growth to explore mechanisms underlying information-seeking. Deprivation curiosity (the tendency to seek information that eliminates knowledge gaps) is associated with the creation of relatively tight networks and a relatively greater tendency to return to previously visited concepts. With this framework in hand, future research can readily quantify the information seeking associated with curiosity.

Reorderability of node-filtered order complexes.

Growing graphs describe a multitude of developing processes from maturing brains to expanding vocabularies to burgeoning public transit systems. Each of these growing processes likely adheres to proliferation rules that establish an effective order of node and connection emergence. When followed, such proliferation rules allow the system to properly develop along a predetermined trajectory. But rules are rarely followed. Here we ask what topological changes in the growing graph trajectories might occur after the specific but basic perturbation of permuting the node emergence order. Specifically, we harness applied topological methods to determine which of six growing graph models exhibit topology that is robust to randomizing node order, termed global reorderability, and robust to temporally local node swaps, termed local reorderability. We find that the six graph models fall upon a spectrum of both local and global reorderability, and furthermore we provide theoretical connections between robustness to node pair ordering and robustness to arbitrary node orderings. Finally, we discuss real-world applications of reorderability analyses and suggest possibilities for designing reorderable networks.

Architecture and evolution of semantic networks in mathematics texts.

Knowledge is a network of interconnected concepts. Yet, precisely how the topological structure of knowledge constrains its acquisition remains unknown, hampering the development of learning enhancement strategies. Here, we study the topological structure of semantic networks reflecting mathematical concepts and their relations in college-level linear algebra texts. We hypothesize that these networks will exhibit structural order, reflecting the logical sequence of topics that ensures accessibility. We find that the networks exhibit strong core-periphery architecture, where a dense core of concepts presented early is complemented with a sparse periphery presented evenly throughout the exposition; the latter is composed of many small modules each reflecting more narrow domains. Using tools from applied topology, we find that the expositional evolution of the semantic networks produces and subsequently fills knowledge gaps, and that the density of these gaps tracks negatively with community ratings of each textbook. Broadly, our study lays the groundwork for future efforts developing optimal design principles for textbook exposition and teaching in a classroom setting.