Richa Tambi

Mohammed Bin Rashid University of Medicine and Health Sciences · College of Medicine

Understanding host cell heterogeneity is critical for unravelling disease mechanism. Utilizing large scale single-cell transcriptomics, we analysed multiple tissue specimens from patients with life-threatening COVID-19 pneumonia, compared with healthy controls. We identified a subtype of monocyte-derived alveolar macrophages (MoAM) where genes asso...

Brugada syndrome (BrS) is a rare, inherited arrhythmia with high risk of sudden cardiac death. To evaluate the molecular convergence of clinically relevant mutations and to identify developmental cardiac cell types that are associated with BrS etiology, we collected 733 mutations represented by 16 sodium, calcium, potassium channels, regulatory and...

In order to investigate the early phase of the amyloid formation by the short amyloidogenic octapeptide sequence (‘NFGAILSS’) derived from IAPP, we carried out a 100ns all-atom molecular dynamics (MD) simulations of systems that contain 27 peptides and over 30,000 water molecules. The large-scale calculations were performed for the wild type sequen...

Mitogen-Activated Protein Kinase Kinase Kinases (MAPKKKs) are important components of MAPK cascades, which are universal signal transduction modules and play important role in plant growth and development. In the sequenced Arabidopsis genome 80 MAPKKKs were identified and currently being analysed for its role in different stress. In rice, economica...

The availability of large scale multi-omics data requires development of computational models to infer valuable biological insights for the implementation of precision medicine. Artificial intelligence (AI) refers to a host of computational algorithms that is becoming a major tool capable of integrating large genomic, transcriptomic, proteomic, and...

Generation of human induced pluripotent stem cells (iPSCs) through reprogramming was a transformational change in the field of regenerative medicine that led to new possibilities for drug discovery and cell replacement therapy. Several protocols have been established to differentiate hiPSCs into neuronal lineages. However, low differentiation effic...

Congenital heart disease (CHD) is one of the most prevalent neonatal congenital anomalies. To catalog the putative candidate CHD risk, we collected 16,349 variants (single nucleotide variants (SNVs) and Indels) impacting 8,308 genes in 3,166 CHD cases for a comprehensive meta-analysis. Using ACMG guidelines we excluded the 0.1% of benign/likely ben...

Neurodevelopmental disorders (NDDs) and congenital anomalies (CAs) are rare disorders with complex etiology. In this study, we investigated the less understood genomic overlap of copy number variants (CNVs) in two large cohorts of NDD and CA patients to identify de novo CNVs and candidate genes associated with both phenotypes. We analyzed clinical...

Neurodevelopmental disorders (NDDs) and congenital anomalies (CAs) are a collection of rare disorders with complex etiology. In this study, we investigated the less understood genomic overlap of copy number variants (CNVs) in two large cohorts of NDD and CA patients to identify de novo CNVs and candidate genes associated to both NDD and CA phenotyp...

Congenital heart disease (CHD) involves cardiovascular malformations and, are one of the most common type of birth defect. The estimated prevalence ranges from ~1-3% of live births and it causes significant mortality worldwide. Although etiology and pathophysiology of CHD remains elusive, genetic factors are known to be a major contributor. In this...

We describe the protocol for identifying COVID-19 severity specific cell types and their regulatory marker genes using single-cell transcriptomics data. We construct COVID-19 comorbid disease associated gene-list using multiple databases and literature resources. Next, we identify specific cell type where comorbid genes are upregulated. We further...

The association of the cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC) in the pathophysiology of cystic fibrosis (CF) is controversial. Previously, we demonstrated a close physical association between wild type (WT) CFTR and WT ENaC. We have also shown that the F508del CFTR fails to associate with ENa...

Background: Although social isolation is known to limit the spread of a pandemic, the impact of mental health for such measures is yet unknown. In this cross-sectional study, we investigated the impact on mental health among different age groups due to social isolation during the ongoing COVID-19 pandemic in Dhaka, Bangladesh. Methods: We conducted...

Understanding structural excursions of proteins under folding conditions is crucial to map energy landscapes of proteins. In the present study, OneG computational tool has been used for analyzing possible existence of cryptic intermediates and metastable states of 26 proteins for which three prerequisite inputs of the OneG such as atomic coordinate...

The advent of long-read sequencing offers a new assessment method of detecting genomic structural variation (SV) in numerous rare genetic diseases. For autism spectrum disorders (ASD) cases where pathogenic variants fail to be found in the protein-coding genic regions along chromosomes, we proposed a scalable workflow to characterize the risk facto...

Background Flexnerism, or “competency-based medical education,” advocates that formal analytic reasoning, the kind of rational thinking fundamental to the basic sciences, especially the natural sciences, should be the foundation of physicians’ intellectual training. The complexity of 21st century health care requires rethinking of current (medical)...

BACKGROUND The involvedness of 21st century healthcare requires re-thinking of current (medical) educational paradigms. In this “Millennial Era” to promulgate the tenets of Flexnerism in undergraduate medical education (UME), requires the design and blueprinting of innovative pedagogical strategies, because the targeted learners are millennials and...

BACKGROUND With the rapid integration of genetics into medicine, it has become evident that practicing physicians as well as medical students and clinical researchers need to be updated on the fundamentals of bioinformatics. To achieve this, the following gaps need to be addressed: a lack of defined learning objectives for “Bioinformatics for Medic...

Background: With the rapid integration of genetics into medicine, it has become evident that practicing physicians as well as medical students and clinical researchers need to be updated on the fundamentals of bioinformatics. To achieve this, the following gaps need to be addressed: a lack of defined learning objectives for "Bioinformatics for Med...

Proteins play cardinal roles in carrying out many biological activities such as immune system reactions, signal transduction, gene expression, storage, translocation and much more. In general, proteins are synthesized in ribosomes of eukaryotic organisms as linear polypeptide chains, which then acquire unique biologically active three-dimensional (...

Efficient and rapid prediction of domain regions from amino acid sequence information alone is often required for swift structural and functional characterization of large multi-domain proteins. Here we introduce Fast H-DROP, a thirty times accelerated version of our previously reported H-DROP (Helical Domain linker pRediction using OPtimal feature...

Aim: Calcium-dependent protein kinases (CDPKs) are Ca²⁺ binding proteins which play a crucial role in plant growth and development, various biotic and abiotic stress and hormone signal transduction pathways through Ca²⁺ signal transduction mechanism. The main objective of the present study was to identify and characterize CDPK gene family from Pige...

Owing to various experimental constraints, detection and characterization of cryptic intermediates (CIs) presumably existing in the unfolding kinetics of barnase and thioredoxin were not successful by native-state hydrogen-deuterium exchange method at pH 6.4, 306 K and pH 7.0, 298 K, respectively. We have herein demonstrated possible existence of C...

Residue-specific stabilities of proteins can be reliably determined by using NMR-monitored hydrogen/deuterium exchange (NMR-H/D) methods under native conditions. Notwithstanding the potential advantages of the NMR-H/D methods, they are time consuming, very expensive and technically challenging. In this review article, various computational tools an...

Understanding structural excursions of proteins under native conditions at residue level resolutions is crucial to map energy landscapes of proteins and also to solve the ‘Levinthal paradox’ of protein folding. Native-state hydrogen–deuterium (NS H/D) exchange methods are powerful to structurally characterize cryptic intermediates (CIs) populating...

Residue-specific stabilities of proteins can be studied by using hydrogen/deuterium exchange methods in conjunction with nuclear magnetic resonance techniques (H/D NMR). Under EX2 exchange conditions, residue-specific equilibrium unfolding constants of residues are ratio of intrinsic exchange rate constants (krc) to extrinsic exchange rate constant...

Unfolding pathways of Pseudomonas aeruginosa cytochrome c551 (Pa cyt c) characterized by native state hydrogen-deuterium exchange (NS H/D) methods in conjunction with multi-dimensional NMR techniques have been reported in the literature. Based on the analyses carried out on the H/D exchange data, it has been shown that there are four submolecular u...

The conformational stability and dynamics of proteins are indispensable to address the structure-function relationships of proteins and also to design novel proteins for therapeutic purposes. At molecular level, conformational stability of a protein can be monitored in presence of external denaturing agents by using traditional biophysical techniqu...

Designing antagonists to anti-apoptotic proteins of Bcl-2 family has become an important strategy in cancer chemotherapy. Using experimental techniques and computational methods, a few numbers of lead inhibitors to the antiapoptotic proteins have been reported in the literature and a few of them are under clinical trials. In this review, the lead i...

Estimation of extrinsic (k ex) and intrinsic (krc) exchange rate constants for labile protons of proteins is indispensable to determine the residues pecific free energies. While k ex of labile protons in proteins are determined by experimental methods, the k rc of those protons are calculated based on the parameters derived from the model compound...

Understanding the relationships between conformations of proteins and their stabilities is one key to address the protein folding paradigm. The free energy change (ΔG) of unfolding reactions of proteins is measured by traditional denaturation methods and native hydrogen-deuterium (H/D) exchange methods. However, the free energy of unfolding (ΔG(U))...

Flowchart depicting the Stage I of OneG. Key-steps used to calculate the krc of NHs in proteins and ΔGHX of proteins are outlined. (TIF)

Flowchart depicting the Stage IV of OneG. The key-steps involved in the OneG algorithm on predicting cryptic intermediates/higher energy metastable in the unfolding kinetics of proteins under native conditions, are shown. (TIF)

Flowchart depicting the Stage II of OneG. The flowchart outlines the key-steps used to account the effect of cis-trans proline isomerisation on the ΔGHX of proteins. (TIF)

Flowchart depicting the Stage III of OneG. The Flowchart enumerates systematically the various steps to frame two-state model equations for appropriately treating the pre- and post-baselines of melting curves of proteins. (TIF)

The thermodynamic stabilities (ΔG, free energy change) of proteins are being measured by traditional denaturation methods (ΔGU, free energy of unfolding) and native hydrogen-deuterium (H/D) exchange method (ΔGHX, free energy of exchange), in general. Estimation of an accurate ΔG for proteins at ambient conditions is indispensable to unambiguously a...