Article
Immunology
Mats Ohlin
Summary: Extensive diversity is present in the human heavy chain immunoglobulin locus, with some genes previously thought to be commonly deleted actually being expressed at low levels in multiple haplotypes. However, these genes harbor sequence variants within their coding region that may compromise their functionality, limiting their incorporation into the immunoglobulin repertoire. This suggests that the functionality status of immunoglobulin genes should also consider their ability to encode fully functional protein products.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Aastha Vatsyayan, Parul Sharma, Shrey Gupta, Sumiti Sandhu, Seetha Lakshmi Venu, Vandana Sharma, Bouabid Badaoui, Kaidi Azedine, Serti Youssef, Anna Rajab, Alaaeldin Fayez, Seema Madinur, Anop Ranawat, Kavita Pandhare, Srinivasan Ramachandran, Sridhar Sivasubbu, Vinod Scaria
Summary: The Arab population has genetic diversity and high prevalence of certain genetic diseases, yet lacks a database for clinical relevant genetic variants. The DALIA database aims to fill this gap by providing a comprehensive resource for genetic variant analyses and aiding clinical interpretation, genetic epidemiology, rapid screening, and evaluation of genetic diseases.
Article
Biochemistry & Molecular Biology
Jing Tang, Xianglu Wu, Minjie Mou, Chuan Wang, Lidan Wang, Fengcheng Li, Maiyuan Guo, Jiayi Yin, Wenqin Xie, Xiaona Wang, Yingxiong Wang, Yubin Ding, Weiwei Xue, Feng Zhu
Summary: This study focuses on the impact of environmental factors on microbial community composition, highlighting the roles of host factors in shaping human microbiota. Host factors are categorized into host genetic factors (HGFs) and host immune factors (HIFs), with a database called 'GIMICA' established to collect and organize these factors for comprehensive health management. By providing information on how these factors define the landscapes inhabited by microbiota, the database allows for a holistic consideration of different types of host factors as well as the interactions between host and environmental factors.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Cell Biology
Benjamin Alleva, Kevin Brick, Florencia Pratto, Mini Huang, Rafael Daniel Camerini-Otero
Summary: PRDM9 protein plays a critical role in determining meiotic recombination sites in humans. The diversity of PRDM9 is important for understanding human population genetics, inheritance linkage patterns, and predisposition to genetic disease. The hypervariable zinc finger array of PRDM9 leads to potentially different DNA binding preferences among alleles.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Christian A. Devaux, Jacques Fantini
Summary: Since the start of the SARS-CoV-2 pandemic, the virus has been evolving through mutation selection in response to both the immune system and cellular receptors, leading to the emergence of variants that can escape neutralization.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Genetics & Heredity
Ye Chen, Yuyan Wang, Ping Zhou, Hao Huang, Rui Li, Zhen Zeng, Zifeng Cui, Rui Tian, Zhuang Jin, Jiashuo Liu, Zhaoyue Huang, Lifang Li, Zheying Huang, Xun Tian, Meiying Yu, Zheng Hu
Summary: This study constructed a virus integration site (VIS) Atlas database, which collected integration breakpoints for three most prevalent oncoviruses. The database provides a genome browser, a platform to discover integration patterns, and a statistics interface for a comprehensive investigation of genotype specific integration features.
GENOMICS PROTEOMICS & BIOINFORMATICS
(2023)
Article
Multidisciplinary Sciences
Andrea Morger, Marina Garcia de Lomana, Ulf Norinder, Fredrik Svensson, Johannes Kirchmair, Miriam Mathea, Andrea Volkamer
Summary: This study evaluates the performance of internally valid conformal prediction models when applied to either newer time-split data or external data. The study analyzes temporal data drifts and investigates discrepancies between models trained on publicly-available data and applied to proprietary data. The study finds a decrease in model validity when applied to the new or external test sets, but this can be improved by updating the calibration set.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Zbigniew J. Krol, Paula Dobosz, Antonina Slubowska, Magdalena Mroczek
Summary: Initially, exome sequencing was expected to uncover the genetic basis of most heritable diseases. However, attention has shifted to the non-coding sequences that make up 98% of the genome and have important regulatory functions. The release of whole-genome sequencing datasets, including underrepresented populations, and the recognition of the importance of local databases have further enhanced the potential of genomic databases in diagnostics, therapies, and various fields of research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Marzieh Eslami Rasekh, Yozen Hernandez, Samantha D. Drinan, Juan I. Fuxman Bass, Gary Benson
Summary: VNTRs are tandem repeat loci that vary in copy number across a population. Commonly polymorphic VNTR loci, enriched in genomic regions with regulatory function, can be used for population ancestry classification and show correlation with gene expression differences.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Immunology
Zhaoli Liu, Gizem Kilic, Wenchao Li, Ozlem Bulut, Manoj Kumar Gupta, Bowen Zhang, Cancan Qi, He Peng, Hsin-Chieh Tsay, Chai Fen Soon, Yonatan Ayalew Mekonnen, Anaisa Valido Ferreira, Caspar I. van der Made, Bram van Cranenbroek, Hans J. P. M. Koenen, Elles Simonetti, Dimitri Diavatopoulos, Marien I. de Jonge, Lisa Mueller, Heiner Schaal, Philipp N. Ostermann, Markus Cornberg, Britta Eiz-Vesper, Frank van de Veerdonk, Reinout van Crevel, Leo A. B. Joosten, Jorge Dominguez-Andres, Cheng-Jian Xu, Mihai G. Netea, Yang Li
Summary: Through a multi-omics study, it was found that although minor differences exist in immunological responses, the immune system of convalescent COVID-19 patients largely recovers to the level of healthy individuals.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemical Research Methods
Wouter De Coster, Rosa Rademakers
Summary: As the cohort size in long-read sequencing projects grows, there is a need for more efficient software to handle and evaluate sequencing data from Oxford Nanopore Technologies and Pacific Biosciences. This article presents novel tools for summarizing experiments, filtering datasets, visualizing phased alignments results, and updates to the NanoPack software suite.
Review
Gastroenterology & Hepatology
Qiao Zhan, Jing-Hang Xu, Yan-Yan Yu, Emily K. N. Lo, Felicianna, Hani El-Nezami, Zheng Zeng
Summary: This review summarizes the methodology and application of immune repertoire sequencing (IRS) in studying the human immune system, focusing on its role in predicting the progression, treatment, and vaccination of Hepatitis B virus (HBV) infection.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Immunology
Ziyi Chen, Han Na, Aiping Wu
Summary: Immune cell composition varies significantly across different tissues and diseases. Computational methods have been developed to estimate immune cell abundance from tissue transcriptome data, allowing for large-scale estimation of immune cell composition across tissues and conditions. ImmuCellDB is a database that provides users with immune cell proportions based on tissues, disease or genotype in mouse or humans, as well as the correlation between immune cell abundance and gene expression level under different conditions.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Erica G. Schmitt, Megan A. Cooper
Summary: Primary immunodeficiency diseases (PIDs) are a rapidly growing group of genetically determined diseases characterized by immune system defects. Despite being individually rare, PIDs collectively affect a significant portion of the global population. Studying the genetic mechanisms of PIDs has advanced our understanding of host response to infections, autoimmunity, and autoinflammation.
ANNUAL REVIEW OF IMMUNOLOGY, VOL 39
(2021)
Article
Biotechnology & Applied Microbiology
Maria Esther Nieto-Blazquez, Dennis Schreiber, Sarah A. Mueller, Katrin Koch, Carsten Nowak, Markus Pfenninger
Summary: This study investigates the genetic structure, demographic history, population differentiation, and domestic introgression of the endangered European wildcat in Germany. The results show evidence of recent anthropogenic impact on the genetic structure, including population divergence due to persecution and potential adaptation to human-dominated environments. However, the species also shows resistance to major anthropogenic impacts such as domestic introgression and inbreeding.
Article
Biology
Meghan E. Garrett, Jared G. Galloway, Caitlin Wolf, Jennifer K. Logue, Nicholas Franko, Helen Y. Chu, Frederick A. Matsen, Julie M. Overbaugh
Summary: When SARS-CoV-2 evolves, existing antibodies may lose their ability to bind effectively, reducing the protection offered by past infection or vaccination. The study found that there are differences in antibodies produced in response to different levels of infection and vaccination, which could help minimize the emergence of antibody-evading mutations. Using a phage display library technique, researchers explored the binding of antibodies to different parts of the SARS-CoV-2 spike protein. The results showed that antibodies produced after vaccination bind to certain regions of the spike protein, while antibodies from mild infection target fewer areas. These findings can guide vaccine development and the data has been made accessible to other scientists and the public.
Article
Biochemical Research Methods
Kenneth B. Hoehn, Oliver G. Pybus, Steven H. Kleinstein
Summary: This study developed parsimony-based summary statistics to characterize migration, differentiation, and isotype switching along B cell phylogenetic trees, demonstrating their effectiveness through simulations and application in HIV and allergy patient datasets.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Cell Biology
Andrew M. Collins, Corey T. Watson, Felix Breden
Summary: Reproductive isolation and gene divergence contribute to the formation of new species through Dobzhansky-Muller incompatibilities (DMIs). The nature of vertebrate immunoglobulin (IG) genes makes them prone to DMIs. The coordination of evolution between IG genes and the rest of the genome is critical for avoiding autoimmune disease.
IMMUNOLOGY AND CELL BIOLOGY
(2022)
Article
Virology
Caitlin Stoddard, Kevin Sung, Ednah Ojee, Judith Adhiambo, Emily R. Begnel, Jennifer Slyker, Soren Gantt, Frederick A. Matsen, John Kinuthia, Dalton Wamalwa, Julie Overbaugh, Dara A. Lehman
Summary: This study investigated the relationship between pre-existing antibodies and SARS-CoV-2 infection in mothers and infants. The results showed that pre-existing coronavirus antibodies in mothers increased after SARS-CoV-2 infection, but no increase was observed in infants. This suggests that the response to coronavirus can be boosted by SARS-CoV-2 infection only when a previous memory response has been established.
Article
Immunology
Rui Yang, Danielle T. Avery, Katherine J. L. Jackson, Masato Ogishi, Ibtihal Benhsaien, Likun Du, Xiaofei Ye, Jing Han, Jeremie Rosain, Jessica N. Peel, Marie-Alexandra Alyanakian, Benedicte Neven, Sarah Winter, Anne Puel, Bertrand Boisson, Kathryn J. Payne, Melanie Wong, Amanda J. Russell, Yoko Mizoguchi, Satoshi Okada, Gulbu Uzel, Christopher C. Goodnow, Sylvain Latour, Jalila El Bakkouri, Aziz Bousfiha, Kahn Preece, Paul E. Gray, Baerbel Keller, Klaus Warnatz, Stephanie Boisson-Dupuis, Laurent Abel, Qiang Pan-Hammarstrom, Jacinta Bustamante, Cindy S. Ma, Jean-Laurent Casanova, Stuart G. Tangye
Summary: This study describes a patient with inherited T-bet deficiency who showed largely normal humoral immunity but exhibited skewed class switching and a specific subset of B cell development. T-bet was found to play an essential role in the development of a distinct subset of human B cells characterized by reduced expression of CD21 and high expression of CD19, CD20, CD11c, FCRL5, and T-bet.
SCIENCE IMMUNOLOGY
(2022)
Article
Biochemical Research Methods
Branden J. Olson, Stefan A. Schattgen, Paul G. Thomas, Philip Bradley, Frederick A. Matsen
Summary: This paper introduces a nonparametric approach for comparing TCR repertoires using the Sinkhorn distance as an optimal transport method and the recently-created TCR distance called TCRdist. The authors demonstrate that their methods can identify meaningful differences between TCR distributions and compete with more complicated methods.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Biochemical Research Methods
Duncan K. Ralph, Frederick A. Matsen
Summary: Next generation sequencing of the B cell receptor (BCR) repertoire has become a common tool for studying the immune response mediated by antibodies. However, previous sequencing data lacked information on pairing the two domains of a functional antibody. This paper presents methods to improve the analysis of paired data, solving the problem of clonal family inference and correcting imperfect pairing information.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Evolutionary Biology
Mathieu Fourment, Christiaan J. Swanepoel, Jared G. Galloway, Xiang Ji, Karthik Gangavarapu, Marc A. Suchard, Frederick A. Matsen
Summary: Gradients of probabilistic model likelihoods are crucial for computational statistics and machine learning. General-purpose machine-learning libraries like TensorFlow and PyTorch offer automatic differentiation for arbitrary models. However, for phylogenetic cases, these libraries may be slower compared to specialized code. This paper compares six gradient implementations and finds that automatic differentiation is slower than carefully implemented methods. A mixed approach combining phylogenetic libraries and machine learning libraries is recommended for optimal speed and model flexibility.
GENOME BIOLOGY AND EVOLUTION
(2023)
Article
Immunology
Kevin M. Nickerson, Shuchi Smita, Kenneth B. Hoehn, Anthony D. Marinov, Kayla B. Thomas, Justin T. Kos, Yi Yang, Sheldon I. Bastacky, Corey T. Watson, Steven H. Kleinstein, Mark J. Shlomchik
Summary: Age-associated B cells (ABCs) are a type of memory B cell expressing the transcription factor T-bet, formed under inflammatory conditions. In systemic lupus erythematosus (SLE), ABC frequency is correlated with disease and they are considered the source of autoantibody-secreting cells. The heterogeneity of ABCs and their relationship to other B cell subsets such as plasmablasts is unclear. The study shows that ABCs are dynamic and can be plasmablast precursors or undergo cycles of reactivation. Deletion of CD11c-expressing B cells reveals a direct role for ABC-like B cells in lupus pathogenesis.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Biology
Will Dumm, Mary Barker, William Howard-Snyder, William S. Dewitt III, Frederick A. Matsen IV
Summary: This paper introduces a novel object, called the history subpartition directed acyclic graph (history sDAG), which compactly represents an ensemble of trees and allows efficient identification of additional equally parsimonious trees, expanding the framework of uncertainty quantification.
JOURNAL OF MATHEMATICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ayelet Peres, William D. Lees, Oscar L. Rodriguez, Noah Y. Lee, Pazit Polak, Ronen Hope, Meirav Kedmi, Andrew M. Collins, Mats Ohlin, Steven H. Kleinstein, Corey T. Watson, Gur Yaari
Summary: In adaptive immune receptor repertoire analysis, determining the germline variable (V) allele associated with each T- and B-cell receptor sequence is challenging. In this study, we propose an alternative naming scheme for V alleles and a novel method to infer individual genotypes. We validate the effectiveness of our approach and implement it in a freely available R package (PIgLET).
NUCLEIC ACIDS RESEARCH
(2023)
Article
Evolutionary Biology
Jakub Truszkowski, Allison Perrigo, David Broman, Fredrik Ronquist, Alexandre Antonelli
Summary: Bayesian phylogenetics faces challenges due to its computational expense and the increasing amount of genomic data. However, new approaches such as online phylogenetics and alternatives to Markov chain Monte Carlo (MCMC) offer potential solutions to scale up Bayesian analyses. Collaborative efforts are needed to develop methods for real-time tree expansion through online phylogenetics.
SYSTEMATIC BIOLOGY
(2023)
Article
Biochemical Research Methods
Jared G. Galloway, Kevin Sung, Samuel S. Minot, Meghan E. Garrett, Caitlin Stoddard, Alexandra C. Willcox, Zak A. Yaffe, Ryan Yucha, Julie Overbaugh, Frederick A. Matsen
Summary: We present the phippery software suite, which consists of a Nextflow pipeline, a Python API, and a Streamlit application, for analyzing data from PhIP-Seq methods. It enables processing of raw sequencing data, calculation of enrichment, and visualization of data as a heatmap.
