GPCR-BSD: a database of binding sites of human G-protein coupled receptors under diverse states.

G-protein coupled receptors (GPCRs), the largest family of membrane proteins in human body, involve a great variety of biological processes and thus have become highly valuable drug targets. By binding with ligands (e.g.

Predicting functional effect of missense variants using graph attention neural networks.

Accurate prediction of damaging missense variants is critically important for interpreting a genome sequence. Although many methods have been developed, their performance has been limited. Recent advances in machine learning and the availability of large-scale population genomic sequencing data provide new opportunities to considerably improve computational predictions.

Protein Structure Prediction: Challenges, Advances, and the Shift of Research Paradigms.

Protein structure prediction is an interdisciplinary research topic that has attracted researchers from multiple fields, including biochemistry, medicine, physics, mathematics, and computer science. These researchers adopt various research paradigms to attack the same structure prediction problem: biochemists and physicists attempt to reveal the principles governing protein folding; mathematicians, especially statisticians, usually start from assuming a probability distribution of protein structures given a target sequence and then find the most likely structure, while computer scientists formulate protein structure prediction as an optimization problem - finding the structural conformation with the lowest energy or minimizing the difference between predicted structure and native structure. These research paradigms fall into the two statistical modeling cultures proposed by Leo Breiman, namely, data modeling and algorithmic modeling.

Accurate and efficient protein sequence design through learning concise local environment of residues.

Motivation: Computational protein sequence design has been widely applied in rational protein engineering and increasing the design accuracy and efficiency is highly desired.

Results: Here, we present ProDESIGN-LE, an accurate and efficient approach to protein sequence design. ProDESIGN-LE adopts a concise but informative representation of the residue's local environment and trains a transformer to learn the correlation between local environment of residues and their amino acid types.

Microblog-HAN: A micro-blog rumor detection model based on heterogeneous graph attention network.

Although social media has highly facilitated people's daily communication and dissemination of information, it has unfortunately been an ideal hotbed for the breeding and dissemination of Internet rumors. Therefore, automatically monitoring rumor dissemination in the early stage is of great practical significance. However, the existing detection methods fail to take full advantage of the semantics of the microblog information propagation graph.

FALCON2: a web server for high-quality prediction of protein tertiary structures.

Background: Accurate prediction of protein tertiary structures is highly desired as the knowledge of protein structures provides invaluable insights into protein functions. We have designed two approaches to protein structure prediction, including a template-based modeling approach (called ProALIGN) and an ab initio prediction approach (called ProFOLD). Briefly speaking, ProALIGN aligns a target protein with templates through exploiting the patterns of context-specific alignment motifs and then builds the final structure with reference to the homologous templates.

MVP predicts the pathogenicity of missense variants by deep learning.

Accurate pathogenicity prediction of missense variants is critically important in genetic studies and clinical diagnosis. Previously published prediction methods have facilitated the interpretation of missense variants but have limited performance. Here, we describe MVP (Missense Variant Pathogenicity prediction), a new prediction method that uses deep residual network to leverage large training data sets and many correlated predictors.

Template-based prediction of protein structure with deep learning.

Background: Accurate prediction of protein structure is fundamentally important to understand biological function of proteins. Template-based modeling, including protein threading and homology modeling, is a popular method for protein tertiary structure prediction. However, accurate template-query alignment and template selection are still very challenging, especially for the proteins with only distant homologs available.

Correction to: Predicting protein inter-residue contacts using composite likelihood maximization and deep learning.

Following publication of the original article [1], the author explained that there are several errors in the original article.

Predicting protein inter-residue contacts using composite likelihood maximization and deep learning.

Background: Accurate prediction of inter-residue contacts of a protein is important to calculating its tertiary structure. Analysis of co-evolutionary events among residues has been proved effective in inferring inter-residue contacts. The Markov random field (MRF) technique, although being widely used for contact prediction, suffers from the following dilemma: the actual likelihood function of MRF is accurate but time-consuming to calculate; in contrast, approximations to the actual likelihood, say pseudo-likelihood, are efficient to calculate but inaccurate.

Constructing effective energy functions for protein structure prediction through broadening attraction-basin and reverse Monte Carlo sampling.

Background: The ab initio approaches to protein structure prediction usually employ the Monte Carlo technique to search the structural conformation that has the lowest energy. However, the widely-used energy functions are usually ineffective for conformation search. How to construct an effective energy function remains a challenging task.

Improving protein fold recognition by extracting fold-specific features from predicted residue-residue contacts.

Motivation: Accurate recognition of protein fold types is a key step for template-based prediction of protein structures. The existing approaches to fold recognition mainly exploit the features derived from alignments of query protein against templates. These approaches have been shown to be successful for fold recognition at family level, but usually failed at superfamily/fold levels.

Improving prediction of burial state of residues by exploiting correlation among residues.

Background: Residues in a protein might be buried inside or exposed to the solvent surrounding the protein. The buried residues usually form hydrophobic cores to maintain the structural integrity of proteins while the exposed residues are tightly related to protein functions. Thus, the accurate prediction of solvent accessibility of residues will greatly facilitate our understanding of both structure and functionalities of proteins.

Insights into the transmission of respiratory infectious diseases through empirical human contact networks.

In this study, we present representative human contact networks among Chinese college students. Unlike schools in the US, human contacts within Chinese colleges are extremely clustered, partly due to the highly organized lifestyle of Chinese college students. Simulations of influenza spreading across real contact networks are in good accordance with real influenza records; however, epidemic simulations across idealized scale-free or small-world networks show considerable overestimation of disease prevalence, thus challenging the widely-applied idealized human contact models in epidemiology.

Improving residue-residue contact prediction via low-rank and sparse decomposition of residue correlation matrix.

Strategies for correlation analysis in protein contact prediction often encounter two challenges, namely, the indirect coupling among residues, and the background correlations mainly caused by phylogenetic biases. While various studies have been conducted on how to disentangle indirect coupling, the removal of background correlations still remains unresolved. Here, we present an approach for removing background correlations via low-rank and sparse decomposition (LRS) of a residue correlation matrix.

FALCON@home: a high-throughput protein structure prediction server based on remote homologue recognition.

Summary: The protein structure prediction approaches can be categorized into template-based modeling (including homology modeling and threading) and free modeling. However, the existing threading tools perform poorly on remote homologous proteins. Thus, improving fold recognition for remote homologous proteins remains a challenge.