Spatial metatranscriptomics resolves host-bacteria-fungi interactomes.

The interactions of microorganisms among themselves and with their multicellular host take place at the microscale, forming complex networks and spatial patterns. Existing technology does not allow the simultaneous investigation of spatial interactions between a host and the multitude of its colonizing microorganisms, which limits our understanding of host-microorganism interactions within a plant or animal tissue. Here we present spatial metatranscriptomics (SmT), a sequencing-based approach that leverages 16S/18S/ITS/poly-d(T) multimodal arrays for simultaneous host transcriptome- and microbiome-wide characterization of tissues at 55-µm resolution.

Targeted nanoparticles modify neutrophil function .

Neutrophils play critical roles in a broad spectrum of clinical conditions. Accordingly, manipulation of neutrophil function may provide a powerful immunotherapeutic approach. However, due to neutrophils characteristic short half-life and their large population number, this possibility was considered impractical.

Commensal Pseudomonas strains facilitate protective response against pathogens in the host plant.

The community structure in the plant-associated microbiome depends collectively on host-microbe, microbe-microbe and host-microbe-microbe interactions. The ensemble of interactions between the host and microbial consortia may lead to outcomes that are not easily predicted from pairwise interactions. Plant-microbe-microbe interactions are important to plant health but could depend on both host and microbe strain variation.

Commensal Pseudomonas protect Arabidopsis thaliana from a coexisting pathogen via multiple lineage-dependent mechanisms.

Plants are protected from pathogens not only by their own immunity but often also by colonizing commensal microbes. In Arabidopsis thaliana, a group of cryptically pathogenic Pseudomonas strains often dominates local populations. This group coexists in nature with commensal Pseudomonas strains that can blunt the deleterious effects of the pathogens in the laboratory.

Motifier: An IgOme Profiler Based on Peptide Motifs Using Machine Learning.

Antibodies provide a comprehensive record of the encounters with threats and insults to the immune system. The ability to examine the repertoire of antibodies in serum and discover those that best represent "discriminating features" characteristic of various clinical situations, is potentially very useful. Recently, phage display technologies combined with Next-Generation Sequencing (NGS) produced a powerful experimental methodology, coined "Deep-Panning", in which the spectrum of serum antibodies is probed.

PredictProtein - Predicting Protein Structure and Function for 29 Years.

Since 1992 PredictProtein (https://predictprotein.org) is a one-stop online resource for protein sequence analysis with its main site hosted at the Luxembourg Centre for Systems Biomedicine (LCSB) and queried monthly by over 3,000 users in 2020. PredictProtein was the first Internet server for protein predictions.

Domain-Scan: Combinatorial Sero-Diagnosis of Infectious Diseases Using Machine Learning.

The presence of pathogen-specific antibodies in an individual's blood-sample is used as an indication of previous exposure and infection to that specific pathogen (e.g., virus or bacterium).

A Truncated Singleton NLR Causes Hybrid Necrosis in Arabidopsis thaliana.

Hybrid necrosis in plants arises from conflict between divergent alleles of immunity genes contributed by different parents, resulting in autoimmunity. We investigate a severe hybrid necrosis case in Arabidopsis thaliana, where the hybrid does not develop past the cotyledon stage and dies 3 weeks after sowing. Massive transcriptional changes take place in the hybrid, including the upregulation of most NLR (nucleotide-binding site leucine-rich repeat) disease-resistance genes.

ConSurf-DB: An accessible repository for the evolutionary conservation patterns of the majority of PDB proteins.

Patterns observed by examining the evolutionary relationships among proteins of common origin can reveal the structural and functional importance of specific residue positions. In particular, amino acids that are highly conserved (i.e.

Broad phylogenetic analysis of cation/proton antiporters reveals transport determinants.

Cation/proton antiporters (CPAs) play a major role in maintaining living cells' homeostasis. CPAs are commonly divided into two main groups, CPA1 and CPA2, and are further characterized by two main phenotypes: ion selectivity and electrogenicity. However, tracing the evolutionary relationships of these transporters is challenging because of the high diversity within CPAs.

A Simulation-Based Approach to Statistical Alignment.

Classic alignment algorithms utilize scoring functions which maximize similarity or minimize edit distances. These scoring functions account for both insertion-deletion (indel) and substitution events. In contrast, alignments based on stochastic models aim to explicitly describe the evolutionary dynamics of sequences by inferring relevant probabilistic parameters from input sequences.

ASAP - A Webserver for Immunoglobulin-Sequencing Analysis Pipeline.

Reproducible and robust data on antibody repertoires are invaluable for basic and applied immunology. Next-generation sequencing (NGS) of antibody variable regions has emerged as a powerful tool in systems immunology, providing quantitative molecular information on antibody polyclonal composition. However, major computational challenges exist when analyzing antibody sequences, from error handling to hypermutation profiles and clonal expansion analyses.

Multiple Sequence Alignment Averaging Improves Phylogeny Reconstruction.

The classic methodology of inferring a phylogenetic tree from sequence data is composed of two steps. First, a multiple sequence alignment (MSA) is computed. Then, a tree is reconstructed assuming the MSA is correct.

Phage display peptide libraries: deviations from randomness and correctives.

Peptide-expressing phage display libraries are widely used for the interrogation of antibodies. Affinity selected peptides are then analyzed to discover epitope mimetics, or are subjected to computational algorithms for epitope prediction. A critical assumption for these applications is the random representation of amino acids in the initial naïve peptide library.

SpartaABC: a web server to simulate sequences with indel parameters inferred using an approximate Bayesian computation algorithm.

Many analyses for the detection of biological phenomena rely on a multiple sequence alignment as input. The results of such analyses are often further studied through parametric bootstrap procedures, using sequence simulators. One of the problems with conducting such simulation studies is that users currently have no means to decide which insertion and deletion (indel) parameters to choose, so that the resulting sequences mimic biological data.

TraitRateProp: a web server for the detection of trait-dependent evolutionary rate shifts in sequence sites.

Understanding species adaptation at the molecular level has been a central goal of evolutionary biology and genomics research. This important task becomes increasingly relevant with the constant rise in both genotypic and phenotypic data availabilities. The TraitRateProp web server offers a unique perspective into this task by allowing the detection of associations between sequence evolution rate and whole-organism phenotypes.

Inferring Rates and Length-Distributions of Indels Using Approximate Bayesian Computation.

The most common evolutionary events at the molecular level are single-base substitutions, as well as insertions and deletions (indels) of short DNA segments. A large body of research has been devoted to develop probabilistic substitution models and to infer their parameters using likelihood and Bayesian approaches. In contrast, relatively little has been done to model indel dynamics, probably due to the difficulty in writing explicit likelihood functions.

ConSurf 2016: an improved methodology to estimate and visualize evolutionary conservation in macromolecules.

The degree of evolutionary conservation of an amino acid in a protein or a nucleic acid in DNA/RNA reflects a balance between its natural tendency to mutate and the overall need to retain the structural integrity and function of the macromolecule. The ConSurf web server (http://consurf.tau.

Inferring Indel Parameters using a Simulation-based Approach.

In this study, we present a novel methodology to infer indel parameters from multiple sequence alignments (MSAs) based on simulations. Our algorithm searches for the set of evolutionary parameters describing indel dynamics which best fits a given input MSA. In each step of the search, we use parametric bootstraps and the Mahalanobis distance to estimate how well a proposed set of parameters fits input data.

ConTemplate Suggests Possible Alternative Conformations for a Query Protein of Known Structure.

Protein function involves conformational changes, but often, for a given protein, only some of these conformations are known. The missing conformations could be predicted using the wealth of data in the PDB. Most PDB proteins have multiple structures, and proteins sharing one similar conformation often share others as well.

GUIDANCE2: accurate detection of unreliable alignment regions accounting for the uncertainty of multiple parameters.

Inference of multiple sequence alignments (MSAs) is a critical part of phylogenetic and comparative genomics studies. However, from the same set of sequences different MSAs are often inferred, depending on the methodologies used and the assumed parameters. Much effort has recently been devoted to improving the ability to identify unreliable alignment regions.

Indel reliability in indel-based phylogenetic inference.

It is often assumed that it is unlikely that the same insertion or deletion (indel) event occurred at the same position in two independent evolutionary lineages, and thus, indel-based inference of phylogeny should be less subject to homoplasy compared with standard inference which is based on substitution events. Indeed, indels were successfully used to solve debated evolutionary relationships among various taxonomical groups. However, indels are never directly observed but rather inferred from the alignment and thus indel-based inference may be sensitive to alignment errors.

PredictProtein--an open resource for online prediction of protein structural and functional features.

PredictProtein is a meta-service for sequence analysis that has been predicting structural and functional features of proteins since 1992. Queried with a protein sequence it returns: multiple sequence alignments, predicted aspects of structure (secondary structure, solvent accessibility, transmembrane helices (TMSEG) and strands, coiled-coil regions, disulfide bonds and disordered regions) and function. The service incorporates analysis methods for the identification of functional regions (ConSurf), homology-based inference of Gene Ontology terms (metastudent), comprehensive subcellular localization prediction (LocTree3), protein-protein binding sites (ISIS2), protein-polynucleotide binding sites (SomeNA) and predictions of the effect of point mutations (non-synonymous SNPs) on protein function (SNAP2).

CoPAP: Coevolution of presence-absence patterns.

Evolutionary analysis of phyletic patterns (phylogenetic profiles) is widely used in biology, representing presence or absence of characters such as genes, restriction sites, introns, indels and methylation sites. The phyletic pattern observed in extant genomes is the result of ancestral gain and loss events along the phylogenetic tree. Here we present CoPAP (coevolution of presence-absence patterns), a user-friendly web server, which performs accurate inference of coevolving characters as manifested by co-occurring gains and losses.