Antibody-Antigen Binding Interface Analysis in the Big Data Era
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ABSTRACT:
SUBMITTER: Reis P
PROVIDER: S-EPMC9329859 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC8021051 | biostudies-literature
Project description:Structure-based vaccine design depends on extensive structural analyses of antigen-antibody complexes.Single-particle electron cryomicroscopy (cryoEM) can circumvent some of the problems of x-ray crystallography as a pipeline for obtaining the required structures. We have examined the potential of single-particle cryoEM for determining the structure of influenza-virus hemagglutinin (HA):single-chain variable-domain fragment complexes, by studying a complex we failed to crystallize in pursuing an extended project on the human immune response to influenza vaccines.The result shows that a combination of cryoEM and molecular modeling can yield details of the antigen-antibody interface, although small variation in the twist of the rod-likeHA trimer limited the overall resolution to about 4.5Å.Comparison of principal 3D classes suggests ways to modify the HA trimer to overcome this limitation. A closely related antibody from the same donor did yield crystals when bound with the same HA, giving us an independent validation of the cryoEM results.The two structures also augment our understanding of receptor-binding site recognition by antibodies that neutralize a wide range of influenza-virus variants.
| S-EPMC5535819 | biostudies-literature
Project description:High-throughput B-cell sequencing has opened up new avenues for investigating complex mechanisms underlying our adaptive immune response. These technological advances drive data generation and the need to mine and analyze the information contained in these large datasets, in particular the identification of therapeutic antibodies (Abs) or those associated with disease exposure and protection. Here, we describe our efforts to use artificial intelligence (AI)-based image-analyses for prospective classification of Abs based solely on sequence information. We hypothesized that Abs recognizing the same part of an antigen share a limited set of features at the binding interface, and that the binding site regions of these Abs share share common structure and physicochemical property patterns that can serve as a "fingerprint" to recognize uncharacterized Abs. We combined large-scale sequence-based protein-structure predictions to generate ensembles of 3-D Ab models, reduced the Ab binding interface to a 2-D image (fingerprint), used pre-trained convolutional neural networks to extract features, and trained deep neural networks (DNNs) to classify Abs. We evaluated this approach using Ab sequences derived from human HIV and Ebola viral infections to differentiate between two Abs, Abs belonging to specific B-cell family lineages, and Abs with different epitope preferences. In addition, we explored a different type of DNN method to detect one class of Abs from a larger pool of Abs. Testing on Ab sets that had been kept aside during model training, we achieved average prediction accuracies ranging from 71-96% depending on the complexity of the classification task. The high level of accuracies reached during these classification tests suggests that the DNN models were able to learn a series of structural patterns shared by Abs belonging to the same class. The developed methodology provides a means to apply AI-based image recognition techniques to analyze high-throughput B-cell sequencing datasets (repertoires) for Ab classification.
| S-EPMC8032195 | biostudies-literature
Project description:Imputation is a powerful in silico approach to fill in those missing values in the big datasets. This process requires a reference panel, which is a collection of big data from which the missing information can be extracted and imputed. Haplotype imputation requires ethnicity-matched references; a mismatched reference panel will significantly reduce the quality of imputation. However, currently existing big datasets cover only a small number of ethnicities, there is a lack of ethnicity-matched references for many ethnic populations in the world, which has hampered the data imputation of haplotypes and its downstream applications. To solve this issue, several approaches have been proposed and explored, including the mixed reference panel, the internal reference panel and genotype-converted reference panel. This review article provides the information and comparison between these approaches. Increasing evidence showed that not just one or two genetic elements dictate the gene activity and functions; instead, cis-interactions of multiple elements dictate gene activity. Cis-interactions require the interacting elements to be on the same chromosome molecule, therefore, haplotype analysis is essential for the investigation of cis-interactions among multiple genetic variants at different loci, and appears to be especially important for studying the common diseases. It will be valuable in a wide spectrum of applications from academic research, to clinical diagnosis, prevention, treatment, and pharmaceutical industry.
| S-EPMC4888899 | biostudies-literature
Project description:This data article presents an analysis of structural water molecules in the high affinity interaction between a potent tumor growth inhibiting antibody (fragment), J22.9-xi, and the tumor marker antigen CD269 (B cell maturation antigen, BCMA). The 1.89 Å X-ray crystal structure shows exquisite details of the binding interface between the two molecules, which comprises relatively few, mostly hydrophobic, direct contacts but many indirect interactions over solvent waters. These are partly or wholly buried in, and therefore part of, the interface. A partial description of the structure is included in an article on the tumor inhibiting effects of the antibody: "Potent anti-tumor response by targeting B cell maturation antigen (BCMA) in a mouse model of multiple myeloma", Mol. Oncol. 9 (7) (2015) pp. 1348-58.
| S-EPMC4707293 | biostudies-literature
Project description:With the increasing availability of large amounts of data in the livestock domain, we face the challenge to store, combine and analyse these data efficiently. With this study, we explored the use of a data lake for storing and analysing data to improve scalability and interoperability. Data originated from a 2-day animal experiment in which the gait score of approximately 200 turkeys was determined through visual inspection by an expert. Additionally, inertial measurement units (IMUs), a 3D-video camera and a force plate (FP) were installed to explore the effectiveness of these sensors in automating the visual gait scoring. We deployed a data lake using the IMU and FP data of a single day of that animal experiment. This encompasses data from 84 turkeys for which we preprocessed by performing an 'extract, transform and load' (ETL-) procedure. To test scalability of the ETL-procedure, we simulated increasing volumes of the available data from this animal experiment and computed the 'wall time' (elapsed real time) for converting FP data into comma-separated files and storing these files. With a simulated data set of 30 000 turkeys, the wall time reduced from 1 h to less than 15 min, when 12 cores were used compared to 1 core. This demonstrated the ETL-procedure to be scalable. Subsequently, a machine learning (ML) pipeline was developed to test the potential of a data lake to automatically distinguish between two classses, that is, very bad gait scores v. other scores. In conclusion, we have set up a dedicated customized data lake, loaded data and developed a prediction model via the creation of an ML pipeline. A data lake appears to be a useful tool to face the challenge of storing, combining and analysing increasing volumes of data of varying nature in an effective manner.
| S-EPMC7538337 | biostudies-literature
Project description:Felsenstein's application of the bootstrap method to evolutionary trees is one of the most cited scientific papers of all time. The bootstrap method, which is based on resampling and replications, is used extensively to assess the robustness of phylogenetic inferences. However, increasing numbers of sequences are now available for a wide variety of species, and phylogenies based on hundreds or thousands of taxa are becoming routine. With phylogenies of this size Felsenstein's bootstrap tends to yield very low supports, especially on deep branches. Here we propose a new version of the phylogenetic bootstrap in which the presence of inferred branches in replications is measured using a gradual 'transfer' distance rather than the binary presence or absence index used in Felsenstein's original version. The resulting supports are higher and do not induce falsely supported branches. The application of our method to large mammal, HIV and simulated datasets reveals their phylogenetic signals, whereas Felsenstein's bootstrap fails to do so.
| S-EPMC6030568 | biostudies-literature
Project description:Often times terms such as Big Data, increasing digital footprints in the Internet accompanied with advancing analytical techniques, represent a major opportunity to improve public health surveillance and delivery of interventions. However, early adaption of Big Data in other fields revealed ethical challenges that could undermine privacy and autonomy of individuals and cause stigmatization. This chapter aims to identify the benefits and risks associated with the public health application of Big Data through ethical lenses. In doing so, it highlights the need for ethical discussion and framework towards an effective utilization of technologies. We then discuss key strategies to mitigate potentially harmful aspects of Big Data to facilitate its safe and effective implementation.
| S-EPMC7121834 | biostudies-literature
Project description:Engineering efforts are currently attempting to build devices capable of collecting neural activity from one million neurons in the brain. Part of this effort focuses on developing dense multiple-electrode arrays, which require post-processing via 'spike sorting' to extract neural spike trains from the raw signal. Gathering information at this scale will facilitate fascinating science, but these dreams are only realizable if the spike sorting procedure and data pipeline are computationally scalable, at or superior to hand processing, and scientifically reproducible. These challenges are all being amplified as the data scale continues to increase. In this review, recent efforts to attack these challenges are discussed, which have primarily focused on increasing accuracy and reliability while being computationally scalable. These goals are addressed by adding additional stages to the data processing pipeline and using divide-and-conquer algorithmic approaches. These recent developments should prove useful to most research groups regardless of data scale, not just for cutting-edge devices.
| S-EPMC7702194 | biostudies-literature
Project description:BackgroundLatin America harbors some of the most biodiverse countries in the world, including Colombia. Despite the increasing use of cutting-edge technologies in genomics and bioinformatics in several biological science fields around the world, the region has fallen behind in the inclusion of these approaches in biodiversity studies. In this study, we used data mining methods to search in four main public databases of genetic sequences such as: NCBI Nucleotide and BioProject, Pathosystems Resource Integration Center, and Barcode of Life Data Systems databases. We aimed to determine how much of the Colombian biodiversity is contained in genetic data stored in these public databases and how much of this information has been generated by national institutions. Additionally, we compared this data for Colombia with other countries of high biodiversity in Latin America, such as Brazil, Argentina, Costa Rica, Mexico, and Peru.ResultsIn Nucleotide, we found that 66.84% of total records for Colombia have been published at the national level, and this data represents less than 5% of the total number of species reported for the country. In BioProject, 70.46% of records were generated by national institutions and the great majority of them is represented by microorganisms. In BOLD Systems, 26% of records have been submitted by national institutions, representing 258 species for Colombia. This number of species reported for Colombia span approximately 0.46% of the total biodiversity reported for the country (56,343 species). Finally, in PATRIC database, 13.25% of the reported sequences were contributed by national institutions. Colombia has a better biodiversity representation in public databases in comparison to other Latin American countries, like Costa Rica and Peru. Mexico and Argentina have the highest representation of species at the national level, despite Brazil and Colombia, which actually hold the first and second places in biodiversity worldwide.ConclusionsOur findings show gaps in the representation of the Colombian biodiversity at the molecular and genetic levels in widely consulted public databases. National funding for high-throughput molecular research, NGS technologies costs, and access to genetic resources are limiting factors. This fact should be taken as an opportunity to foster the development of collaborative projects between research groups in the Latin American region to study the vast biodiversity of these countries using 'omics' technologies.
| S-EPMC6288850 | biostudies-literature