A5027931169- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Prenatal Screening and Diagnostics
- Genomic variations and chromosomal abnormalities
- Genomics and Chromatin Dynamics
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Nicotinic Acetylcholine Receptors Study
- COVID-19 Clinical Research Studies
- Receptor Mechanisms and Signaling
- Single-cell and spatial transcriptomics
- Long-Term Effects of COVID-19
- Sepsis Diagnosis and Treatment
- SARS-CoV-2 and COVID-19 Research
- Epigenetics and DNA Methylation
- Immune cells in cancer
- Immunodeficiency and Autoimmune Disorders
- Hematopoietic Stem Cell Transplantation
- Craniofacial Disorders and Treatments
- RNA Research and Splicing
- Viral Infectious Diseases and Gene Expression in Insects
- COVID-19 and healthcare impacts
- Developmental Biology and Gene Regulation
- Colorectal Cancer Surgical Treatments
GigaGen (United States)
2010-2022
Grifols (United States)
2022
Institut de Virologie
2021
UPMC Health System
2021
University of Pittsburgh
2021
Public Health Scotland
2021
University of Dundee
2021
Medical Research Council
2021
National Health and Medical Research Council
2021
Intensive Care National Audit & Research Centre
2021
We present Model-based Analysis of ChIP-Seq data, MACS, which analyzes data generated by short read sequencers such as Solexa's Genome Analyzer. MACS empirically models the shift size tags, and uses it to improve spatial resolution predicted binding sites. also a dynamic Poisson distribution effectively capture local biases in genome, allowing for more robust predictions. compares favorably existing peak-finding algorithms, is freely available.
In vivo protein-DNA interactions connect each transcription factor with its direct targets to form a gene network scaffold. To map these comprehensively across entire mammalian genomes, we developed large-scale chromatin immunoprecipitation assay (ChIPSeq) based on ultrahigh-throughput DNA sequencing. This sequence census method was then used in binding of the neuron-restrictive silencer (NRSF; also known as REST, for repressor element–1 silencing factor) 1946 locations human genome. The...
To investigate the role of DNA methylation during human development, we developed Methyl-seq, a method that assays at more than 90,000 regions throughout genome. Performing Methyl-seq on embryonic stem cells (hESCs), their derivatives, and tissues allowed us to identify several trends hESC in vivo liver differentiation. First, differentiation results changes minimal number assayed regions, both vitro (2%–11%). Second, is characterized by de novo demethylation, whereas fetal development...
Preimplantation genetic screening (PGS) has been used in an attempt to determine embryonic aneuploidy. Techniques that use new molecular methods the karyotype of embryo are expanding scope PGS.We introduce a method for PGS, termed 'parental support', which leverages microarray measurements from parental DNA 'clean' single-cell on cells and explicitly computes confidence each copy number call. The distinguishes mitotic meiotic errors determines source aneuploidy.Validation with 459 single...
Abstract Aneuploidy has been well-documented in blastocyst embryos, but prior studies have limited scale and/or lack mechanistic data. We previously reported preclinical validation of microarray 24-chromosome preimplantation genetic screening a 24-h protocol. The method diagnoses chromosome copy number, structural aberrations, parental source aneuploidy and distinguishes certain meiotic from mitotic errors. In this study, our objective was to examine human blastocysts determine...
Through a study of cloned nicotinic receptors expressed in Xenopus oocytes, we provide evidence that alpha-conotoxin ImI, peptide marine snail toxin induces seizures rodents, selectively blocks subtypes acetylcholine receptors. alpha-Conotoxin ImI homomeric alpha 7 with the highest apparent affinity and 9 8-fold lower affinity. This has no effect on composed 2 beta 2, 3 4 4, or subunit combinations. In contrast to alpha-bungarotoxin, which high for 7, 9, 1 gamma delta receptors, low muscle...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCharacterization of the .omega.-conotoxin target. Evidence for tissue-specific heterogeneity in calcium channel typesLourdes J. Cruz, David S. Johnson, and Baldomero M. OliveraCite this: Biochemistry 1987, 26, 3, 820–824Publication Date (Print):February 1, 1987Publication History Published online1 May 2002Published inissue 1 February 1987https://pubs.acs.org/doi/10.1021/bi00377a024https://doi.org/10.1021/bi00377a024research-articleACS...
The most widely used method for detecting genome-wide protein–DNA interactions is chromatin immunoprecipitation on tiling microarrays, commonly known as ChIP-chip. Here, we conducted the first objective analysis of array platforms, amplification procedures, and signal detection algorithms in a simulated ChIP-chip experiment. Mixtures human genomic DNA “spike-ins” comprised nearly 100 sequences at various concentrations were hybridized to four platforms by eight independent groups. Blind...
Transcriptional coexpression of interacting gene products is required for complex molecular processes; however, the function and evolution cis-regulatory elements that orchestrate remain largely unexplored. We mutagenized 19 regulatory drive Ciona muscle genes obtained quantitative estimates activity 77 motifs comprise these elements. found individual motif ranges broadly within among elements, different instantiations same type. The orthologous strongly constrained, although arrangement,...
Promoters are important regulatory elements that contain the necessary sequence features for cells to initiate transcription. To functionally characterize a large set of human promoters, we measured transcriptional activities 4575 putative promoters across eight cell lines using transient transfection reporter assays. In parallel, gene expression in same and observed significant correlation between promoter activity endogenous ( r = 0.43). As assays directly measure promoting effect defined...
Although there is considerable indirect evidence indicating that virilizing testicular tumors exert their effects by producing androgenic steroid hor- mones, few attempts have been made to determine the exact nature of compounds produced.One type tumor which exerts particularly marked when found in prepubertal boys classified as an interstitial cell testes (1-21).It has well established * This work was supported Contracts no.
The study and manipulation of T cell receptors (TCRs) is central to multiple fields across basic translational immunology research. Produced by V(D)J recombination, TCRs are often only recorded in the literature data repositories as a combination their V J gene symbols, plus hypervariable CDR3 amino acid sequence. However, numerous applications require full-length coding nucleotide sequences. Here we present Stitchr, software tool developed specifically address this limitation. Given minimal...
The antibody drug field has continually sought improvements to methods for candidate discovery and engineering. Historically, most such have been laboratory-based, but informatics recently started make an impact. Deep learning, a subfield of machine is rapidly gaining prominence in the biomedical research. Recent advances microfluidics technologies next-generation sequencing not only revolutionized therapeutic discovery, also contributed vast amount repertoire data, providing opportunities...
Though cell therapy for cancer is now widely used commercially and has been efficacious tens of thousands patients, conventional manufacturing methods are expensive difficult to scale. An alternative approach deliver the relevant anti-tumor transgenes T cells in vivo patient. Such promise be more scalable, with reduced cost goods, since same drug product can administered any Typically, introduces into using a lentivector pseudotyped VSV-G. However, VSV-G not type specific because its...
Immunization of mice followed by hybridoma or B-cell screening is one the most common antibody discovery methods used to generate therapeutic monoclonal (mAb) candidates. There are a multitude different immunization protocols that can an immune response in animals. However, extensive analysis repertoires these alternative has not been performed. In this study, we immunized transgenically express human antibodies with either programmed cell death 1 protein cytotoxic T-lymphocyte associated 4...
We show that sequence comparisons at different levels of resolution can efficiently guide functional analyses regulatory regions in the ascidians Ciona savignyi and intestinalis . Sequence alignments several tissue-specific genes guided discovery minimal are active whole-embryo reporter assays. Using Troponin I ( TnI ) locus as a case study, we more refined local then be used to reveal substructure within region. A high-resolution saturation mutagenesis conjunction with comparative defined...
Purpose The metaphase karyotype is often used as a diagnostic tool in the setting of early miscarriage; however this technique has several limitations. We evaluate new for karyotyping that uses single nucleotide polymorphism microarrays (SNP). This was compared blinded, prospective fashion, to traditional karyotype. Methods Patients undergoing dilation and curettage first trimester miscarriage between February August 2010 were enrolled. Samples chorionic villi equally divided sent microarray...
Affinity-matured, functional anti-pathogen antibodies are present at low frequencies in natural human repertoires. These often excellent candidates for therapeutic monoclonal antibodies. However, mining antibody repertoires is a challenge. In this study, we demonstrate new method that uses microfluidics, yeast display, and deep sequencing to identify 247 natively paired single-chain variable fragments (scFvs), which were initially as rare 1 100,000 the Influenza A vaccination increased...
Conventionally, mouse hybridomas or well-plate screening are used to identify therapeutic monoclonal antibody candidates. In this study, we present an alternative hybridoma-based discovery that combines microfluidics, yeast single-chain variable fragment (scFv) display, and deep sequencing rapidly interrogate screen repertoires. We our approach on six wild-type mice 269 molecules bind programmed cell death protein 1 (PD-1), which were at average of in 2,000 the pre-sort scFv libraries. Two...
Deep sequencing and single-chain variable fragment (scFv) yeast display methods are becoming more popular for discovery of therapeutic antibody candidates in mouse B cell repertoires. In this study, we compare a deep scFv method that retains native heavy light chain pairing with related randomly pairs chain. We performed the studies humanized mouse, using interleukin 21 receptor (IL-21R) as test immunogen. identified 44 high-affinity binder 100 random method. 30% natively paired binders were...