抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Complete knowledge of all direct and indirect interactions between proteins in a given cell would represent an important milestone towards a comprehensive description of cellular mechanisms and functions. Although this goal is still elusive, considerable progress has been made-particularly for certain model organisms and functional systems. Currently, protein interactions and associations are annotated at various levels of detail in online resources, ranging from raw data repositories to highly formalized pathway databases. For many applications, a global view of all the available interaction data is desirable, including lower-quality data and/or computational predictions. The STRING database (http://string-db.org/) aims to provide such a global perspective for as many organisms as feasible. Known and predicted associations are scored and integrated, resulting in comprehensive protein networks covering >1100 organisms. Here, we describe the update to version 9.1 of STRING, introducing several improvements: (i) we extend the automated mining of scientific texts for interaction information, to now also include full-text articles; (ii) we entirely re-designed the algorithm for transferring interactions from one model organism to the other; and (iii) we provide users with statistical information on any functional enrichment observed in their networks.

/pdf/string-v9-1-protein-protein-interaction-networks-with-42hnvufk2o.pdf

STRING v9.1: protein-protein interaction networks, with increased coverage and integration

A key challenge of modern biology is to uncover the functional role of the protein entities that compose cellular proteomes. To this end, the availability of reliable three-dimensional atomic models of proteins is often crucial. This protocol presents a community-wide web-based method using RaptorX (
 http://raptorx.uchicago.edu/
 ) for protein secondary structure prediction, template-based tertiary structure modeling, alignment quality assessment and sophisticated probabilistic alignment sampling. RaptorX distinguishes itself from other servers by the quality of the alignment between a target sequence and one or multiple distantly related template proteins (especially those with sparse sequence profiles) and by a novel nonlinear scoring function and a probabilistic-consistency algorithm. Consequently, RaptorX delivers high-quality structural models for many targets with only remote templates. At present, it takes RaptorX ∼35 min to finish processing a sequence of 200 amino acids. Since its official release in August 2011, RaptorX has processed ∼6,000 sequences submitted by ∼1,600 users from around the world.

/pdf/template-based-protein-structure-modeling-using-the-raptorx-3bbosge48e.pdf

Template-based protein structure modeling using the RaptorX web server

This presentation is a case study taken from the travel and holiday industry. Paxport/Multicom, based in UK and Sweden, have recently adopted a recommendation system for holiday accommodation bookings. Machine learning techniques such as Collaborative Filtering have been applied using Python (3.5.1), with Jupyter (4.0.6) as the main framework. Data scale and sparsity present significant challenges in the case study, and so the effectiveness of various techniques are described as well as the performance of Python-based libraries such as Python Data Analysis Library (Pandas), and Scikit-learn (built on NumPy, SciPy and matplotlib). The presentation is suitable for all levels of programmers.

Machine learning with Python

Structural identity is a concept of symmetry in which network nodes are identified according to the network structure and their relationship to other nodes. Structural identity has been studied in theory and practice over the past decades, but only recently has it been addressed with representational learning techniques. This work presents struc2vec, a novel and flexible framework for learning latent representations for the structural identity of nodes. struc2vec uses a hierarchy to measure node similarity at different scales, and constructs a multilayer graph to encode structural similarities and generate structural context for nodes. Numerical experiments indicate that state-of-the-art techniques for learning node representations fail in capturing stronger notions of structural identity, while struc2vec exhibits much superior performance in this task, as it overcomes limitations of prior approaches. As a consequence, numerical experiments indicate that struc2vec improves performance on classification tasks that depend more on structural identity.

struc2vec: Learning Node Representations from Structural Identity

Protein–protein interactions (PPIs) and their networks play a central role in all biological processes. Akin to the complete sequencing of genomes and their comparative analysis, complete descriptions of interactomes and their comparative analysis is fundamental to a deeper understanding of biological processes. A first step in such an analysis is to align two or more PPI networks. Here, we introduce an algorithm, IsoRank, for global alignment of multiple PPI networks. The guiding intuition here is that a protein in one PPI network is a good match for a protein in another network if their respective sequences and neighborhood topologies are a good match. We encode this intuition as an eigenvalue problem in a manner analogous to Google's PageRank method. Using IsoRank, we compute a global alignment of the Saccharomyces cerevisiae, Drosophila melanogaster, Caenorhabditis elegans, Mus musculus, and Homo sapiens PPI networks. We demonstrate that incorporating PPI data in ortholog prediction results in improvements over existing sequence-only approaches and over predictions from local alignments of the yeast and fly networks. Previous methods have been effective at identifying conserved, localized network patterns across pairs of networks. This work takes the further step of performing a global alignment of multiple PPI networks. It simultaneously uses sequence similarity and network data and, unlike previous approaches, explicitly models the tradeoff inherent in combining them. We expect IsoRank—with its simultaneous handling of node similarity and network similarity—to be applicable across many scientific domains.

https://www.pnas.org/content/pnas/105/35/12763.full.pdf

Global alignment of multiple protein interaction networks with application to functional orthology detection.

Motivation: With the increasing availability of large protein–protein interaction networks, the question of protein network alignment is becoming central to systems biology. Network alignment is further delineated into two sub-problems: local alignment, to find small conserved motifs across networks, and global alignment, which attempts to find a best mapping between all nodes of the two networks. In this article, our aim is to improve upon existing global alignment results. Better network alignment will enable, among other things, more accurate identification of functional orthologs across species. Results: We introduce IsoRankN (IsoRank-Nibble) a global multiplenetwork alignment tool based on spectral clustering on the induced graph of pairwise alignment scores. IsoRankN outperforms existing algorithms for global network alignment in coverage and consistency on multiple alignments of the five available eukaryotic networks. Being based on spectral methods, IsoRankN is both error tolerant and computationally efficient. Availability: Our software is available freely for non-commercial purposes on request from: http://isorank.csail.mit.edu/

IsoRankN: spectral methods for global alignment of multiple protein networks

We describe an algorithm, IsoRank, for global alignment of two protein-protein interaction (PPI) networks. IsoRank aims to maximize the overall match between the two networks; in contrast, much of previous work has focused on the local alignment problem-- identifying many possible alignments, each corresponding to a local region of similarity. IsoRank is guided by the intuition that a protein should be matched with a protein in the other network if and only if the neighbors of the two proteins can also be well matched. We encode this intuition as an eigenvalue problem, in a manner analogous to Google's PageRank method. We use IsoRank to compute the first known global alignment between the S. cerevisiae and D. melanogaster PPI networks. The common subgraph has 1420 edges and describes conserved functional components between the two species. Comparisons of our results with those of a well-known algorithm for local network alignment indicate that the globally optimized alignment resolves ambiguity introduced by multiple local alignments. Finally, we interpret the results of global alignment to identify functional orthologs between yeast and fly; our functional ortholog prediction method is much simpler than a recently proposed approach and yet provides results that are more comprehensive.

/pdf/pairwise-global-alignment-of-protein-interaction-networks-by-3ckip6mawk.pdf

Pairwise global alignment of protein interaction networks by matching neighborhood topology

Cover Picture: Engineered SAM Synthetases for Enzymatic Generation of AdoMet Analogs with Photocaging Groups and Reversible DNA Modification in Cascade Reactions (Angew. Chem. Int. Ed. 1/2021)

Struct2Net is a web server for predicting interactions between arbitrary protein pairs using a structure-based approach. Prediction of protein-protein interactions (PPIs) is a central area of interest and successful prediction would provide leads for experiments and drug design; however, the experimental coverage of the PPI interactome remains inadequate. We believe that Struct2Net is the first community-wide resource to provide structure-based PPI predictions that go beyond homology modeling. Also, most web-resources for predicting PPIs currently rely on functional genomic data (e.g. GO annotation, gene expression, cellular localization, etc.). Our structure-based approach is independent of such methods and only requires the sequence information of the proteins being queried. The web service allows multiple querying options, aimed at maximizing flexibility. For the most commonly studied organisms (fly, human and yeast), predictions have been pre-computed and can be retrieved almost instantaneously. For proteins from other species, users have the option of getting a quick-but-approximate result (using orthology over pre-computed results) or having a full-blown computation performed. The web service is freely available at http://struct2net.csail.mit.edu.

/pdf/struct2net-a-web-service-to-predict-protein-protein-1r2u81d0lt.pdf

Rohit Singh

Papers

Global alignment of multiple protein interaction networks with application to functional orthology detection.

IsoRankN: spectral methods for global alignment of multiple protein networks

Pairwise global alignment of protein interaction networks by matching neighborhood topology

Cover Picture: Engineered SAM Synthetases for Enzymatic Generation of AdoMet Analogs with Photocaging Groups and Reversible DNA Modification in Cascade Reactions (Angew. Chem. Int. Ed. 1/2021)

Struct2Net: a web service to predict protein–protein interactions using a structure-based approach