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Repertoire Sequencing

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https://www.readbyqxmd.com/read/29033130/tumor-and-microenvironment-evolution-during-immunotherapy-with-nivolumab
#1
Nadeem Riaz, Jonathan J Havel, Vladimir Makarov, Alexis Desrichard, Walter J Urba, Jennifer S Sims, F Stephen Hodi, Salvador Martín-Algarra, Rajarsi Mandal, William H Sharfman, Shailender Bhatia, Wen-Jen Hwu, Thomas F Gajewski, Craig L Slingluff, Diego Chowell, Sviatoslav M Kendall, Han Chang, Rachna Shah, Fengshen Kuo, Luc G T Morris, John-William Sidhom, Jonathan P Schneck, Christine E Horak, Nils Weinhold, Timothy A Chan
The mechanisms by which immune checkpoint blockade modulates tumor evolution during therapy are unclear. We assessed genomic changes in tumors from 68 patients with advanced melanoma, who progressed on ipilimumab or were ipilimumab-naive, before and after nivolumab initiation (CA209-038 study). Tumors were analyzed by whole-exome, transcriptome, and/or T cell receptor (TCR) sequencing. In responding patients, mutation and neoantigen load were reduced from baseline, and analysis of intratumoral heterogeneity during therapy demonstrated differential clonal evolution within tumors and putative selection against neoantigenic mutations on-therapy...
October 11, 2017: Cell
https://www.readbyqxmd.com/read/29032247/specifications-of-targeting-heterochromatin-modifications-in-plants
#2
REVIEW
Jered M Wendte, Robert J Schmitz
Plants encode a diverse repertoire of DNA methyltransferases that have specialized to target cytosines for methylation in specific sequence contexts. These include the de novo methyltransferase, DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2), which methylates cytosines in all sequence contexts through an RNA guided process, the CHROMOMETHYLASES (CMTs), which methylate CHH and CHG cytosines (where H is A, T, or C), and the maintenance methyltransferase, METHYLTRANSFERASE 1 (MET1), which maintains methylation of symmetrical CG contexts...
October 12, 2017: Molecular Plant
https://www.readbyqxmd.com/read/29031828/non-progressing-cancer-patients-have-persistent-b-cell-responses-expressing-shared-antibody-paratopes-that-target-public-tumor-antigens
#3
Jeff DeFalco, Michael Harbell, Amy Manning-Bog, Gilson Baia, Alexander Scholz, Beatriz Millare, May Sumi, Danhui Zhang, Felix Chu, Christine Dowd, Patricia Zuno-Mitchell, Dongkyoon Kim, Yvonne Leung, Shuwei Jiang, Xiaobin Tang, Kevin S Williamson, Xiaomu Chen, Sean M Carroll, Gregg Espiritu Santo, Nicole Haaser, Ngan Nguyen, Eldar Giladi, David Minor, Yann Chong Tan, Jeremy B Sokolove, Lawrence Steinman, Tito A Serafini, Guy Cavet, Norman M Greenberg, Jacob Glanville, Wayne Volkmuth, Daniel E Emerling, William H Robinson
There is significant debate regarding whether B cells and their antibodies contribute to effective anti-cancer immune responses. Here we show that patients with metastatic but non-progressing melanoma, lung adenocarcinoma, or renal cell carcinoma exhibited increased levels of blood plasmablasts. We used a cell-barcoding technology to sequence their plasmablast antibody repertoires, revealing clonal families of affinity matured B cells that exhibit progressive class switching and persistence over time. Anti-CTLA4 and other treatments were associated with further increases in somatic hypermutation and clonal family size...
October 11, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29029271/sequence-and-structural-diversity-of-mouse-y-chromosomes
#4
Andrew P Morgan, Pardo-Manuel de Villena Fernando
Over the 180 million years since their origin, the sex chromosomes of mammals have evolved a gene repertoire highly specialized for function in the male germline. The mouse Y chromosome is unique among mammalian Y chromosomes characterized to date in that it is large, gene-rich and euchromatic. Yet little is known about its diversity in natural populations. Here we take advantage of published whole-genome sequencing data to survey the diversity of sequence and copy number of sex-linked genes in three subspecies of house mice...
September 25, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/29028876/systematic-comparative-study-of-computational-methods-for-t-cell-receptor-sequencing-data-analysis
#5
Saira Afzal, Irene Gil-Farina, Richard Gabriel, Shahzad Ahmad, Christof von Kalle, Manfred Schmidt, Raffaele Fronza
High-throughput sequencing technologies have exposed the possibilities for the in-depth evaluation of T-cell receptor (TCR) repertoires. These studies are highly relevant to gain insights into human adaptive immunity and to decipher the composition and diversity of antigen receptors in physiological and disease conditions. The major objective of TCR sequencing data analysis is the identification of V, D and J gene segments, complementarity-determining region 3 (CDR3) sequence extraction and clonality analysis...
September 23, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/29020925/vdjpipe-a-pipelined-tool-for-pre-processing-immune-repertoire-sequencing-data
#6
Scott Christley, Mikhail K Levin, Inimary T Toby, John M Fonner, Nancy L Monson, William H Rounds, Florian Rubelt, Walter Scarborough, Richard H Scheuermann, Lindsay G Cowell
BACKGROUND: Pre-processing of high-throughput sequencing data for immune repertoire profiling is essential to insure high quality input for downstream analysis. VDJPipe is a flexible, high-performance tool that can perform multiple pre-processing tasks with just a single pass over the data files. RESULTS: Processing tasks provided by VDJPipe include base composition statistics calculation, read quality statistics calculation, quality filtering, homopolymer filtering, length and nucleotide filtering, paired-read merging, barcode demultiplexing, 5' and 3' PCR primer matching, and duplicate reads collapsing...
October 11, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28993513/dna-vaccination-by-electroporation-amplifies-broadly-cross-restricted-public-tcr-clonotypes-shared-with-hiv-controllers
#7
Madhura Mukhopadhyay, Moran Galperin, Mandar Patgaonkar, Sandhya Vasan, David D Ho, Alexandre Nouël, Mathieu Claireaux, Daniela Benati, Olivier Lambotte, Yaoxing Huang, Lisa A Chakrabarti
Rare patients who spontaneously control HIV replication provide a useful model to inform HIV vaccine development. HIV controllers develop particularly efficient antiviral CD4(+) T cell responses mediated by shared high-affinity TCRs. To determine whether the candidate DNA vaccine ADVAX could induce similar responses, we analyzed Gag-specific primary CD4(+) T cells from healthy volunteers who received ADVAX DNA by electroporation. Vaccinated volunteers had an immunodominant response to the Gag293 epitope with a functional avidity intermediate between that of controllers and treated patients...
October 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28985561/insights-into-land-plant-evolution-garnered-from-the-marchantia-polymorpha-genome
#8
John L Bowman, Takayuki Kohchi, Katsuyuki T Yamato, Jerry Jenkins, Shengqiang Shu, Kimitsune Ishizaki, Shohei Yamaoka, Ryuichi Nishihama, Yasukazu Nakamura, Frédéric Berger, Catherine Adam, Shiori Sugamata Aki, Felix Althoff, Takashi Araki, Mario A Arteaga-Vazquez, Sureshkumar Balasubrmanian, Kerrie Barry, Diane Bauer, Christian R Boehm, Liam Briginshaw, Juan Caballero-Perez, Bruno Catarino, Feng Chen, Shota Chiyoda, Mansi Chovatia, Kevin M Davies, Mihails Delmans, Taku Demura, Tom Dierschke, Liam Dolan, Ana E Dorantes-Acosta, D Magnus Eklund, Stevie N Florent, Eduardo Flores-Sandoval, Asao Fujiyama, Hideya Fukuzawa, Bence Galik, Daniel Grimanelli, Jane Grimwood, Ueli Grossniklaus, Takahiro Hamada, Jim Haseloff, Alexander J Hetherington, Asuka Higo, Yuki Hirakawa, Hope N Hundley, Yoko Ikeda, Keisuke Inoue, Shin-Ichiro Inoue, Sakiko Ishida, Qidong Jia, Mitsuru Kakita, Takehiko Kanazawa, Yosuke Kawai, Tomokazu Kawashima, Megan Kennedy, Keita Kinose, Toshinori Kinoshita, Yuji Kohara, Eri Koide, Kenji Komatsu, Sarah Kopischke, Minoru Kubo, Junko Kyozuka, Ulf Lagercrantz, Shih-Shun Lin, Erika Lindquist, Anna M Lipzen, Chia-Wei Lu, Efraín De Luna, Robert A Martienssen, Naoki Minamino, Masaharu Mizutani, Miya Mizutani, Nobuyoshi Mochizuki, Isabel Monte, Rebecca Mosher, Hideki Nagasaki, Hirofumi Nakagami, Satoshi Naramoto, Kazuhiko Nishitani, Misato Ohtani, Takashi Okamoto, Masaki Okumura, Jeremy Phillips, Bernardo Pollak, Anke Reinders, Moritz Rövekamp, Ryosuke Sano, Shinichiro Sawa, Marc W Schmid, Makoto Shirakawa, Roberto Solano, Alexander Spunde, Noriyuki Suetsugu, Sumio Sugano, Akifumi Sugiyama, Rui Sun, Yutaka Suzuki, Mizuki Takenaka, Daisuke Takezawa, Hirokazu Tomogane, Masayuki Tsuzuki, Takashi Ueda, Masaaki Umeda, John M Ward, Yuichiro Watanabe, Kazufumi Yazaki, Ryusuke Yokoyama, Yoshihiro Yoshitake, Izumi Yotsui, Sabine Zachgo, Jeremy Schmutz
The evolution of land flora transformed the terrestrial environment. Land plants evolved from an ancestral charophycean alga from which they inherited developmental, biochemical, and cell biological attributes. Additional biochemical and physiological adaptations to land, and a life cycle with an alternation between multicellular haploid and diploid generations that facilitated efficient dispersal of desiccation tolerant spores, evolved in the ancestral land plant. We analyzed the genome of the liverwort Marchantia polymorpha, a member of a basal land plant lineage...
October 5, 2017: Cell
https://www.readbyqxmd.com/read/28985418/the-systemhc-atlas-project
#9
Wenguang Shao, Patrick G A Pedrioli, Witold Wolski, Cristian Scurtescu, Emanuel Schmid, Juan A Vizcaíno, Mathieu Courcelles, Heiko Schuster, Daniel Kowalewski, Fabio Marino, Cecilia S L Arlehamn, Kerrie Vaughan, Bjoern Peters, Alessandro Sette, Tom H M Ottenhoff, Krista E Meijgaarden, Natalie Nieuwenhuizen, Stefan H E Kaufmann, Ralph Schlapbach, John C Castle, Alexey I Nesvizhskii, Morten Nielsen, Eric W Deutsch, David S Campbell, Robert L Moritz, Roman A Zubarev, Anders Jimmy Ytterberg, Anthony W Purcell, Miguel Marcilla, Alberto Paradela, Qi Wang, Catherine E Costello, Nicola Ternette, Peter A van Veelen, Cécile A C M van Els, Albert J R Heck, Gustavo A de Souza, Ludvig M Sollid, Arie Admon, Stefan Stevanovic, Hans-Georg Rammensee, Pierre Thibault, Claude Perreault, Michal Bassani-Sternberg, Ruedi Aebersold, Etienne Caron
Mass spectrometry (MS)-based immunopeptidomics investigates the repertoire of peptides presented at the cell surface by major histocompatibility complex (MHC) molecules. The broad clinical relevance of MHC-associated peptides, e.g. in precision medicine, provides a strong rationale for the large-scale generation of immunopeptidomic datasets and recent developments in MS-based peptide analysis technologies now support the generation of the required data. Importantly, the availability of diverse immunopeptidomic datasets has resulted in an increasing need to standardize, store and exchange this type of data to enable better collaborations among researchers, to advance the field more efficiently and to establish quality measures required for the meaningful comparison of datasets...
July 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28984021/conotoxin-%C3%AE-mixxviia-from-the-new-superfamily-g2-employs-a-novel-cysteine-framework-that-mimics-granulin-and-displays-anti-apoptotic-activity
#10
Ai-Hua Jin, Zoltan Dekan, Michael J Smout, David Wilson, Sébastien Dutertre, Irina Vetter, Richard J Lewis, Alex Loukas, Norelle L Daly, Paul Francis Alewood
Conotoxins are a large family of disulfide-rich peptides that contain unique cysteine frameworks that target a broad range of ion channels and receptors. We recently discovered the 33-residue conotoxin Φ-MiXXVIIA from Conus miles with a novel cysteine framework comprising three consecutive cysteine residues and four disulfide bonds. Regioselective chemical synthesis helped decipher the disulfide bond connectivity and the structure of Φ-MiXXVIIA was determined by NMR spectroscopy. The 3D structure displays a unique topology containing two β-hairpins that resemble the N-terminal domain of granulin...
October 5, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28983085/sequence-analysis-of-feline-immunoglobulin-mrnas-and-the-development-of-a-felinized-monoclonal-antibody-specific-to-feline-panleukopenia-virus
#11
Zhengchun Lu, Rebecca L Tallmadge, Heather M Callaway, M Julia B Felippe, John S L Parker
In response to immunization, B-cells generate a repertoire of antigen-specific antibodies. Antibody-based immunotherapies hold great promise for treating a variety of diseases in humans. Application of antibody-based immunotherapy in cats is limited by the lack of species-specific complete sequences for mRNAs encoding rearranged heavy and light chain immunoglobulins in B cells. To address this barrier, we isolated mRNAs from feline peripheral blood mononuclear cells (PBMCs), and used available immunoglobulin sequences and 5' and 3' RACE to clone and sequence heavy and light chain immunoglobulin mRNAs...
October 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28982170/a-combined-transcriptome-and-proteome-analysis-extends-the-allergome-of-house-dust-mite-dermatophagoides-species
#12
Véronique Bordas-Le Floch, Maxime Le Mignon, Laetitia Bussières, Karine Jain, Armelle Martelet, Véronique Baron-Bodo, Emmanuel Nony, Laurent Mascarell, Philippe Moingeon
BACKGROUND: House dust mites (HDMs) such as Dermatophagoides farinae and D. pteronyssinus represent major causes of perennial allergy. HDM proteomes are currently poorly characterized, with information mostly restricted to allergens. As of today, 33 distinct allergen groups have been identified for these 2 mite species, with groups 1 and 2 established as major allergens. Given the multiplicity of IgE-reactive mite proteins, potential additional allergens have likely been overlooked. OBJECTIVE: To perform a comprehensive characterization of the transcriptomes, proteomes and allergomes of D...
2017: PloS One
https://www.readbyqxmd.com/read/28977923/integrated-analysis-of-somatic-mutations-and-immune-microenvironment-of-multiple-regions-in-breast-cancers
#13
Taigo Kato, Jae-Hyun Park, Kazuma Kiyotani, Yuji Ikeda, Yasuo Miyoshi, Yusuke Nakamura
Next-generation sequencing technology enables us to analyze the complexity of intra- and inter-tumoral heterogeneity, which may influence to prognosis of cancer patients. In this study, we collected surgically-resected tumor tissues from five breast cancer patients and characterized three different portions of individual tumors through somatic mutation analysis by whole exome sequencing, T cell receptor beta (TCRB) repertoire analysis of tumor-infiltrating lymphocytes (TILs), and the expression analysis of immune-related genes at 15 different sites...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977646/vdjdb-a-curated-database-of-t-cell-receptor-sequences-with-known-antigen-specificity
#14
Mikhail Shugay, Dmitriy V Bagaev, Ivan V Zvyagin, Renske M Vroomans, Jeremy Chase Crawford, Garry Dolton, Ekaterina A Komech, Anastasiya L Sycheva, Anna E Koneva, Evgeniy S Egorov, Alexey V Eliseev, Ewald Van Dyk, Pradyot Dash, Meriem Attaf, Cristina Rius, Kristin Ladell, James E McLaren, Katherine K Matthews, E Bridie Clemens, Daniel C Douek, Fabio Luciani, Debbie van Baarle, Katherine Kedzierska, Can Kesmir, Paul G Thomas, David A Price, Andrew K Sewell, Dmitriy M Chudakov
The ability to decode antigen specificities encapsulated in the sequences of rearranged T-cell receptor (TCR) genes is critical for our understanding of the adaptive immune system and promises significant advances in the field of translational medicine. Recent developments in high-throughput sequencing methods (immune repertoire sequencing technology, or RepSeq) and single-cell RNA sequencing technology have allowed us to obtain huge numbers of TCR sequences from donor samples and link them to T-cell phenotypes...
September 1, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28977556/programming-sites-of-meiotic-crossovers-using-spo11-fusion-proteins
#15
Roberta Sarno, Yoan Vicq, Norio Uematsu, Marine Luka, Clement Lapierre, Dana Carroll, Giacomo Bastianelli, Alexandre Serero, Alain Nicolas
Meiotic recombination shapes the genetic diversity transmitted upon sexual reproduction. However, its non-random distribution along the chromosomes constrains the landscape of potential genetic combinations. For a variety of purposes, it is desirable to expand the natural repertoire by changing the distribution of crossovers in a wide range of eukaryotes. Toward this end, we report the local stimulation of meiotic recombination at a number of chromosomal sites by tethering the natural Spo11 protein to various DNA-binding modules: full-length DNA binding proteins, zinc fingers (ZFs), transcription activator-like effector (TALE) modules, and the CRISPR-Cas9 system...
August 24, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28973917/root-associated-fungal-microbiota-of-nonmycorrhizal-arabis-alpina-and-its-contribution-to-plant-phosphorus-nutrition
#16
Juliana Almario, Ganga Jeena, Jörg Wunder, Gregor Langen, Alga Zuccaro, George Coupland, Marcel Bucher
Most land plants live in association with arbuscular mycorrhizal (AM) fungi and rely on this symbiosis to scavenge phosphorus (P) from soil. The ability to establish this partnership has been lost in some plant lineages like the Brassicaceae, which raises the question of what alternative nutrition strategies such plants have to grow in P-impoverished soils. To understand the contribution of plant-microbiota interactions, we studied the root-associated fungal microbiome of Arabis alpina (Brassicaceae) with the hypothesis that some of its components can promote plant P acquisition...
October 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28972863/diversity-of-class-1-integrons-and-disruption-of-caro-and-dacd-by-insertion-sequences-among-acinetobacter-baumannii-isolates-in-tehran-iran
#17
Maryam Mirshekar, Fereshteh Shahcheraghi, Omid Azizi, Hamid Solgi, Farzad Badmasti
Acinetobacter baumannii is an important nosocomial pathogen which causes a wide range of infections. In this study, we addressed the role of class 1 integron, ISAba1 and ISAba125 associated with antimicrobial resistance in 72 clinical isolates of A. baumannii collected from clinical settings in Tehran, Iran. Moreover, to study the clonal relatedness of strains, repetitive extragenic palindromic-PCR (rep-PCR) assay was carried out. PCR revealed that blaOXA-51-like, blaOXA-23-like, blaOXA-24/40-like, blaOXA-58-like, blaNDM, integrase gene (intI1), ISAba1, and ISAba125 were present in 86...
October 3, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28970488/single-cell-analysis-reveals-sexually-dimorphic-repertoires-of-interferon-%C3%AE-and-il-17a-producing-t-cells-in-salivary-glands-of-sj%C3%A3-gren-s-syndrome-mice
#18
Arun Wanchoo, Alexandria Voigt, Sukesh Sukumaran, Carol M Stewart, Indraneel Bhattacharya, Cuong Q Nguyen
The development of Sjögren's syndrome (SjS) is a dynamic and temporal process with a female predilection. Following the initial influx of immune cells, T cell clusters develop, accelerating the pathology in the salivary glands. Proinflammatory cytokines, IFN-γ and IL-17A, produced by T cells contribute synergistically to the disease. In this study, we examined the sexual dimorphism in cellular infiltrates of the salivary glands by using functional single-cell microengraving analysis. Using high-throughput sequencing, we investigated the clonal diversity of the T cell receptors (TCRs) of infiltrating IFN-γ and IL-17A-producing T cells in male and female SjS-susceptible (SjS(s)) C57BL/6...
October 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28969707/massive-a-to-i-rna-editing-is-common-across-the-metazoa-and-correlates-with-dsrna-abundance
#19
Hagit T Porath, Binyamin A Knisbacher, Eli Eisenberg, Erez Y Levanon
BACKGROUND: Adenosine to inosine (A-to-I) RNA editing is a post-transcriptional modification catalyzed by the ADAR (adenosine deaminase that acts on RNA) enzymes, which are ubiquitously expressed among metazoans. Technical requirements have limited systematic mapping of editing sites to a small number of organisms. Thus, the extent of editing across the metazoan lineage is largely unknown. RESULTS: Here, we apply a computational procedure to search for RNA-sequencing reads containing clusters of editing sites in 21 diverse organisms...
October 2, 2017: Genome Biology
https://www.readbyqxmd.com/read/28968873/comparison-of-methods-for-phylogenetic-b-cell-lineage-inference-using-time-resolved-antibody-repertoire-simulations-absim
#20
Alexander Yermanos, Victor Greiff, Nike Julia Krautler, Ulrike Menzel, Andreas Dounas, Enkelejda Miho, Annette Oxenius, Tanja Stadler, Sai T Reddy
Motivation: The evolution of antibody repertoires represents a hallmark feature of adaptive B-cell immunity. Recent advancements in high-throughput sequencing have dramatically increased the resolution to which we can measure the molecular diversity of antibody repertoires, thereby offering for the first time the possibility to capture the antigen-driven evolution of B cells. However, there does not exist a repertoire simulation framework yet that enables the comparison of commonly utilized phylogenetic methods with regard to their accuracy in inferring antibody evolution...
August 31, 2017: Bioinformatics
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