Li Xiao

Bio: Li Xiao is an academic researcher from Chinese Academy of Sciences. The author has contributed to research in topics: Artificial neural network & Backpropagation. The author has an hindex of 12, co-authored 48 publications receiving 565 citations. Previous affiliations of Li Xiao include Peking University & Zhengzhou University.

Recent Developments and Applications of the MMPBSA Method.

Abstract: The Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) approach has been widely applied as an efficient and reliable free energy simulation method to model molecular recognition, such as for protein-ligand binding interactions. In this review, we focus on recent developments and applications of the MMPBSA method. The methodology review covers solvation terms, the entropy term, extensions to membrane proteins and high-speed screening, and new automation toolkits. Recent applications in various important biomedical and chemical fields are also reviewed. We conclude with a few future directions aimed at making MMPBSA a more robust and efficient method.

Label-Free Segmentation of COVID-19 Lesions in Lung CT

Abstract: Scarcity of annotated images hampers the building of automated solution for reliable COVID-19 diagnosis and evaluation from CT. To alleviate the burden of data annotation, we herein present a label-free approach for segmenting COVID-19 lesions in CT via voxel-level anomaly modeling that mines out the relevant knowledge from normal CT lung scans. Our modeling is inspired by the observation that the parts of tracheae and vessels, which lay in the high-intensity range where lesions belong to, exhibit strong patterns. To facilitate the learning of such patterns at a voxel level, we synthesize ‘lesions’ using a set of simple operations and insert the synthesized ‘lesions’ into normal CT lung scans to form training pairs, from which we learn a normalcy-recognizing network (NormNet) that recognizes normal tissues and separate them from possible COVID-19 lesions. Our experiments on three different public datasets validate the effectiveness of NormNet, which conspicuously outperforms a variety of unsupervised anomaly detection (UAD) methods.

Marginal loss and exclusion loss for partially supervised multi-organ segmentation

Abstract: Annotating multiple organs in medical images is both costly and time-consuming; therefore, existing multi-organ datasets with labels are often low in sample size and mostly partially labeled, that is, a dataset has a few organs labeled but not all organs. In this paper, we investigate how to learn a single multi-organ segmentation network from a union of such datasets. To this end, we propose two types of novel loss function, particularly designed for this scenario: (i) marginal loss and (ii) exclusion loss. Because the background label for a partially labeled image is, in fact, a `merged' label of all unlabelled organs and `true' background (in the sense of full labels), the probability of this `merged' background label is a marginal probability, summing the relevant probabilities before merging. This marginal probability can be plugged into any existing loss function (such as cross entropy loss, Dice loss, etc.) to form a marginal loss. Leveraging the fact that the organs are non-overlapping, we propose the exclusion loss to gauge the dissimilarity between labeled organs and the estimated segmentation of unlabelled organs. Experiments on a union of five benchmark datasets in multi-organ segmentation of liver, spleen, left and right kidneys, and pancreas demonstrate that using our newly proposed loss functions brings a conspicuous performance improvement for state-of-the-art methods without introducing any extra computation.

DifferentialEquations.jl – A Performant and Feature-Rich Ecosystem for Solving Differential Equations in Julia

Abstract: DifferentialEquationsjl is a package for solving differential equations in Julia It covers discrete equations (function maps, discrete stochastic (Gillespie/Markov) simulations), ordinary differential equations, stochastic differential equations, algebraic differential equations, delay differential equations, hybrid differential equations, jump diffusions, and (stochastic) partial differential equations Through extensive use of multiple dispatch, metaprogramming, plot recipes, foreign function interfaces (FFI), and call-overloading, DifferentialEquationsjl offers a unified user interface to solve and analyze various forms of differential equations while not sacrificing features or performance Many modern features are integrated into the solvers, such as allowing arbitrary user-defined number systems for high-precision and arithmetic with physical units, built-in multithreading and parallelism, and symbolic calculation of Jacobians Integrated into the package is an algorithm testing and benchmarking suite to both ensure accuracy and serve as an easy way for researchers to develop and distribute their own methods Together, these features build a highly extendable suite which is feature-rich and highly performant Funding statement: This work was partially supported by NIH grants P50GM76516 and R01GM107264 and NSF grants DMS1562176 and DMS1161621 This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No DGE-1321846, the National Academies of Science, Engineering, and Medicine via the Ford Foundation, and the National Institutes of Health Award T32 EB009418 Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH

Molecular Docking: Shifting Paradigms in Drug Discovery.

Abstract: Molecular docking is an established in silico structure-based method widely used in drug discovery. Docking enables the identification of novel compounds of therapeutic interest, predicting ligand-target interactions at a molecular level, or delineating structure-activity relationships (SAR), without knowing a priori the chemical structure of other target modulators. Although it was originally developed to help understanding the mechanisms of molecular recognition between small and large molecules, uses and applications of docking in drug discovery have heavily changed over the last years. In this review, we describe how molecular docking was firstly applied to assist in drug discovery tasks. Then, we illustrate newer and emergent uses and applications of docking, including prediction of adverse effects, polypharmacology, drug repurposing, and target fishing and profiling, discussing also future applications and further potential of this technique when combined with emergent techniques, such as artificial intelligence.

Recent Developments and Applications of the MMPBSA Method.

Abstract: The Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) approach has been widely applied as an efficient and reliable free energy simulation method to model molecular recognition, such as for protein-ligand binding interactions. In this review, we focus on recent developments and applications of the MMPBSA method. The methodology review covers solvation terms, the entropy term, extensions to membrane proteins and high-speed screening, and new automation toolkits. Recent applications in various important biomedical and chemical fields are also reviewed. We conclude with a few future directions aimed at making MMPBSA a more robust and efficient method.

gmx_MMPBSA: A New Tool to Perform End-State Free Energy Calculations with GROMACS.

Abstract: Molecular mechanics/Poisson-Boltzmann (Generalized-Born) surface area is one of the most popular methods to estimate binding free energies. This method has been proven to balance accuracy and computational efficiency, especially when dealing with large systems. As a result of its popularity, several programs have been developed for performing MM/PB(GB)SA calculations within the GROMACS community. These programs, however, present several limitations. Here we present gmx_MMPBSA, a new tool to perform end-state free energy calculations from GROMACS molecular dynamics trajectories. gmx_MMPBSA provides the user with several options, including binding free energy calculations with different solvation models (PB, GB, or 3D-RISM), stability calculations, computational alanine scanning, entropy corrections, and binding free energy decomposition. Noteworthy, several promising methodologies to calculate relative binding free energies such as alanine scanning with variable dielectric constant and interaction entropy have also been implemented in gmx_MMPBSA. Two additional tools-gmx_MMPBSA_test and gmx_MMPBSA_ana-have been integrated within gmx_MMPBSA to improve its usability. Multiple illustrating examples can be accessed through gmx_MMPBSA_test, while gmx_MMPBSA_ana provides fast, easy, and efficient access to different graphics plotted from gmx_MMPBSA output files. The latest version (v1.4.3, 26/05/2021) is available free of charge (documentation, test files, and tutorials included) at https://github.com/Valdes-Tresanco-MS/gmx_MMPBSA.