A5005547396- Influenza Virus Research Studies
- Respiratory viral infections research
- Monoclonal and Polyclonal Antibodies Research
- Mosquito-borne diseases and control
- Genomics and Chromatin Dynamics
- HIV Research and Treatment
- SARS-CoV-2 and COVID-19 Research
- Viral Infections and Outbreaks Research
- RNA and protein synthesis mechanisms
- Viral gastroenteritis research and epidemiology
- vaccines and immunoinformatics approaches
- Glycosylation and Glycoproteins Research
- Genomics and Phylogenetic Studies
- Virology and Viral Diseases
- Viral Infectious Diseases and Gene Expression in Insects
- Animal Disease Management and Epidemiology
- Protein purification and stability
- Immune Response and Inflammation
- Fibroblast Growth Factor Research
- Bioinformatics and Genomic Networks
- Gene expression and cancer classification
- Viral Infections and Vectors
- Advanced Multi-Objective Optimization Algorithms
- Fungal and yeast genetics research
- CAR-T cell therapy research
Massachusetts Institute of Technology
2014-2024
Singapore-MIT Alliance for Research and Technology
2014-2015
Harvard–MIT Division of Health Sciences and Technology
2009-2011
National Institutes of Health
2005-2009
National Center for Biotechnology Information
2006
Highlights•Structure-guided affinity enhancement of a cross-reactive dengue antibody•mAb neutralizes all four serotypes with low level viral-enhancing activity•Antibody demonstrates in vivo ability to resolve symptoms severe infection•Crystal structure antibody-antigen validates the predicted designsSummaryDengue is most common vector-borne viral disease, causing nearly 400 million infections yearly. Currently there are no approved therapies. Antibody epitopes that elicit weak humoral...
Significance Emerging influenza subtypes, such as the recently identified H7N9 strains, are of considerable public health concern. Although vaccines an important countermeasure, tend to be subtype- and strain-specific, that they may not widely available in event human adaptation spread unanticipated strain or subtype. Additionally, strains have demonstrated ability develop resistance existing antivirals, including oseltamivir. As such, there is a need for novel interventions can treat and/or...
Significance Dengue virus infects more than 200 million people each year, and incidence of severe disease is increasing with no effective countermeasures. We demonstrate in this paper the engineering an antibody that binds to all four serotypes dengue potent activity vitro vivo. also outline a distinct widely applicable approach provides important information on paratope/epitope interface absence crystal structure data, enabling identification amino acids could be mutated. experimentally...
The 2014-2015 H1N1 outbreak in India has reportedly led to 800 fatalities. reported influenza hemagglutinin sequences from indicate that these viruses contain amino acid changes linked enhanced virulence and are potentially antigenically distinct the current vaccine containing 2009 (Cal0709) viral hemagglutinin.
Significance The COVID-19 pandemic continues to ravage our society, posing serious economic, social, health, and educational concerns in communities. Understanding the human humoral immune response infection will greatly inform public health measures help contain spread of disease foreseeable future. Here, we present an orthogonal approach SARS-CoV-2 antibody testing using distinct viral antigens. Using this platform, conducted a community-based analysis patients with varying experiences...
The application of machine learning (ML) models to optimize antibody affinity an antigen is gaining prominence. Unfortunately, the small and biased nature publicly available antibody-antigen interaction datasets makes it challenging build ML model that can accurately predict binding changes due mutations (ΔΔG). Recognizing these inherent limitations, we reformulated problem ask whether capable classifying deleterious vs non-deleterious guide maturation in a practical setting. To test this...
Abstract Background Biologically active sequence motifs often have positional preferences with respect to a genomic landmark. For example, many known transcription factor binding sites (TFBSs) occur within an interval [-300, 0] bases upstream of start site (TSS). Although some programs for identifying exploit information, most them model it only implicitly and ad hoc methods, making unsuitable general motif searches. Results A-GLAM, user-friendly computer program motifs, now incorporates...
The 2009 swine-origin H1N1 influenza, though antigenically novel to the population at time, was similar 1918 pandemic influenza and consequently considered be "archived" in swine species before reemerging humans. Given that H3N2 is another subtype currently circulates human high on WHO preparedness list, we assessed likelihood of reemergence from a non-human host. Using HA sequence features relevant immune recognition, receptor binding transmission have identified several recent H3 strains...
The transcription start site (TSS) has been located for an increasing number of genes across several organisms. Statistical tests have shown that some cis-acting regulatory elements positional preferences with respect to the TSS, but few strategies emerged locating by their preferences. This paper elaborates such a strategy. First, we align promoter regions without gaps, anchoring alignment on each promoter's TSS. Second, apply novel word-specific mask. Third, clustering test related gapless...
Dengue is a widespread viral disease with 3.6 billion people at risk worldwide. Humanized monoclonal antibody (mAb) 513, currently undergoing clinical trials in Singapore, targets an epitope on the envelope protein domain III exposed surface of particle. This potently neutralizes all four dengue virus serotypes humanized mouse model that recapitulates human infection, without signs antibody-mediated enhancement disease. The crystal structure single-chain variable fragment (scFv) 513 bound to...
A number of previous studies have predicted transcription factor binding sites (TFBSs) by exploiting the position genomic landmarks like transcriptional start site (TSS). The studies' methods are generally too computationally intensive for genome-scale investigation, so full potential 'positional regulomics' to discover TFBSs and determine their function remains unknown. Because databases often annotate in DNA sequences, methodical exploitation positional regulomics has become increasingly...
Heparin and the low molecular weight heparins are extensively used as medicinal products to prevent treat formation of venous arterial thrombi. In early 2008, administration some heparin lots was associated with advent severe adverse effects, indicative an anaphylactoid-like response. Application orthogonal analytical tools enabled detection identification contaminant oversulfated chondroitin sulfate (OSCS) reported in our earlier report. Herein, we investigate whether enzymatic...
Nipah Virus (NiV) has been designated as a priority disease with an urgent need for therapeutic development by World Health Organization. The monoclonal antibody m102.4 binds to the immunodominant NiV receptor-binding glycoprotein (GP), and potently neutralizes NiV, indicating its potential agent. Although co-crystal structure of m102.3, derivative, in complex GP related Hendra (HeV) solved, structural interaction between is uncharacterized. Herein, we used structure-guided alanine-scanning...
At times of pandemics, such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, situation demands rapid development and production timelines safe effective vaccines for delivering life-saving medications quickly to patients. Typical biologics relies on using lengthy arduous approach stable single-cell clones. Here, we used an alternative approach, a cell pool that takes only weeks generate compared clone needs several months complete. We employed membrane,...
Abstract Motivation: Many computational methods for identifying regulatory elements use a likelihood ratio between motif and background models. Often, the model of independent bases. At least two different Markov models have been proposed with aim increasing accuracy predicting elements. Both suffer theoretical drawbacks, so this article develops third, context-dependent from fundamental statistical principles. Results: Datasets containing known in eukaryotes provided basis comparing...
The computational methods used for engineering antibodies clinical development have undergone a transformation from three-dimensional structure-guided approaches to artificial-intelligence- and machine-learning-based that leverage the large sequence data space of hundreds millions generated by next-generation sequencing (NGS) studies. Building on wealth available data, we implemented shuffling approach antibody components, using complementarity-determining region (CDR) framework (FWR)...