Gaurav Ahuja

Crypt neurons are a third type of olfactory receptor neurons with a highly unusual "one cell type - one receptor" mode of expression, the same receptor being expressed by the entire population of crypt neurons. Attempts to identify the target region(s) of crypt neurons have been inconclusive so far. We report that TrkA-like immunoreactivity specifi...

Significance Cadaverine and putrescine, two diamines emanating from decaying flesh, are strongly repulsive odors to humans but serve as innate attractive or social cues in other species. Here we show that zebrafish, a vertebrate model system, exhibit powerful and innate avoidance behavior to both diamines, and identify a high-affinity olfactory rec...

Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report h...

The teleost v1r-related ora genes are a small, highly conserved olfactory receptor gene family of only six genes, whose direct orthologues can be identified in lineages as far as that of cartilaginous fish. However, no ligands for fish olfactory receptor class A related genes (ORA) had been uncovered so far. Here we have deorphanized the ORA1 recep...

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Endogenous intracellular allosteric modulators of GPCRs remain largely unexplored, with limited binding and phenotype data available. This gap arises from the lack of robust computational methods for unbiased cavity identification, cavity-specific ligand design, synthesis, and validation across GPCR topology. Here, we developed Gcoupler, an AI-driv...

Endogenous intracellular allosteric modulators of GPCRs remain largely unexplored, with limited binding and phenotype data available. This gap arises from the lack of robust computational methods for unbiased cavity identification, cavity-specific ligand design, synthesis, and validation across GPCR topology. Here, we developed Gcoupler, an AI-driv...

Single-cell RNA-sequencing (scRNA-seq) coupled with robust computational analysis facilitates the characterization of phenotypic heterogeneity within tumors. Current scRNA-seq analysis pipelines are capable of identifying a myriad of malignant and non-malignant cell subtypes from single-cell profiling of tumors. However, given the extent of intra-t...

Single-cell RNA-sequencing (scRNA-seq) coupled with robust computational analysis facilitates the characterization of phenotypic heterogeneity within tumors. Current scRNA-seq analysis pipelines are capable of identifying a myriad of malignant and non-malignant cell subtypes from single-cell profiling of tumors. However, given the extent of intra-t...

Cancer poses a significant global health challenge, characterized by a complex disease progression and disrupted growth regulation. A thorough understanding of cellular and molecular biological mechanisms is essential for developing novel treatments and improving the accuracy of patient survival predictions. While prior studies have leveraged gene...

Single-cell RNA-sequencing (scRNA-seq) coupled with robust computational analysis facilitates the characterization of phenotypic heterogeneity within tumors. Current scRNA-seq analysis pipelines are capable of identifying a myriad of malignant and non-malignant cell subtypes from single-cell profiling of tumors. However, given the extent of intra-t...

DNA is essentially a collection of short nucleotide sequences with a myriad of functionalities. These oligonucleotides are often studied for their function as molecular binding sites, regulatory motifs or sequence probes. The field of Bioinformatics uses a similar concept under the term "k-mers," which is central to various tasks, like comparing th...

Background The hypothalamus, a small yet crucial neuroanatomical structure, integrates external (e.g., environmental) and internal (e.g., physiological/hormonal) stimuli. This integration governs various physiological processes and influences cognitive, emotional, and behavioral outcomes. It serves as a functional bridge between the nervous and end...

Motivation Dysregulation of a gene’s function, either due to mutations or impairments in regulatory networks, often triggers pathological states in the affected tissue. Comprehensive mapping of these apparent gene–pathology relationships is an ever-daunting task, primarily due to genetic pleiotropy and lack of suitable computational approaches. Wit...

Cellular genome is considered a dynamic blueprint of a cell since it encodes genetic information that gets temporally altered due to various endogenous and exogenous insults. Largely, the extent of genomic dynamicity is controlled by the trade‐off between DNA repair processes and the genotoxic potential of the causative agent (genotoxins or potenti...

The hypothalamus, a diminutive yet vital neuroanatomical structure, plays a central role in integrating external (e.g., environmental) and internal (e.g., physiological/hormonal) stimuli that, in turn, govern diverse physiological processes and shape cognition, emotion, and behavior outcomes. It also establishes the functional connection between th...

Carcinogenicity assessment of any compound is a laborious and expensive exercise with several associated ethical and practical concerns. While artificial intelligence (AI) offers promising solutions, unfortunately, it is contingent on several challenges concerning the inadequacy of available experimentally validated (non)carcinogen datasets and var...

The blueprints of developing organs are preset at the early stages of embryogenesis. Transcriptional and epigenetic mechanisms are proposed to preset developmental trajectories. However, we reveal that the competence for the future cardiac fate of human embryonic stem cells (hESCs) is preset in pluripotency by a specialized mRNA translation circuit...

Traditionally, the exogenous allosteric modulators of G protein-coupled receptors (GPCRs) have been extensively investigated due to their pharmacological significance. However, to date, only a handful of endogenous intracellular allosteric modulators are known, that too with inconclusive binding information and their associated phenotypes. This lim...

Exogenous allosteric modulators of GPCRs have been extensively investigated. To date, a few endogenous intracellular allosteric modulators are known with inconclusive binding information and their associated phenotypes. This limited understanding stems from the non-availability of robust computational techniques facilitating automated cavity identi...

Oral squamous cell carcinoma (OSCC) is the second leading cause of cancer-related morbidity and mortality in India. Tobacco, alcohol, poor oral hygiene, and socio-economic factors remain causative for this high prevalence. Identification of non-invasive diagnostic markers tailored for Indian population can facilitate mass screening to reduce overal...

Robust characterization of cellular phenotypes from single-cell gene expression data is of paramount importance in understanding complex biological systems and diseases. Single-cell RNA-seq (scRNA-seq) datasets are inherently noisy due to small amounts of starting RNA. Over the last few years, several methods have been developed to make single-cell...

The complexity of scRNA-sequencing datasets highlights the urgent need for enhanced clustering and visualization methods. Here, we propose Stardust, an iterative, force-directed graph layouting algorithm that enables simultaneous embedding of cells and marker genes. Stardust, for the first time, allows a single stop visualization of cells and marke...

Odorant receptors (ORs) obey mutual exclusivity and monoallelic mode of expression. Efforts are ongoing to decipher the molecular mechanism that drives the ‘one-neuron-one-receptor’ rule of olfaction. Recently, single-cell profiling of olfactory sensory neurons (OSNs) revealed the expression of multiple ORs in the immature neurons, suggesting that...

The identification and characterization of circulating tumor cells (CTCs) are important for gaining insights into the biology of metastatic cancers, monitoring disease progression, and medical management of the disease. The limiting factor in the enrichment of purified CTC populations is their sparse availability, heterogeneity, and altered phenoty...

Upregulation of RNA polymerase I (Pol I) transcription and the overexpression of Pol I transcriptional machinery are crucial molecular alterations favoring malignant transformation. However, the causal molecular mechanism(s) of this aberration remain largely unknown. Here, we found that Pol I transcription and its core machinery are upregulated in...

Inter and intra-tumoral heterogeneity are major stumbling blocks in the treatment of cancer and are responsible for imparting differential drug responses in cancer patients. Recently, the availability of high-throughput screening datasets has paved the way for machine learning based personalized therapy recommendations using the molecular profiles...

The genome of a eukaryotic cell is often vulnerable to both intrinsic and extrinsic threats owing to its constant exposure to a myriad of heterogeneous compounds. Despite the availability of innate DNA damage responses, some genomic lesions trigger malignant transformation of cells. Accurate prediction of carcinogens is an ever-challenging task owi...

Artificial intelligence (AI)-based computational techniques allow rapid exploration of the chemical space. However, representation of the compounds into computational-compatible and detailed features is one of the crucial steps for quantitative structure–activity relationship (QSAR) analysis. Recently, graph-based methods are emerging as a powerful...

In eukaryotic cells, miRNAs regulate a plethora of cellular functionalities ranging from cellular metabolisms, and development to the regulation of biological networks and pathways, both under homeostatic and pathological states like cancer.Despite their immense importance as key regulators of cellular processes, accurate and reliable estimation of...

Cancers are caused by genomic alterations that may be inherited, induced by environmental carcinogens, or caused due to random replication errors. Post-induction of carcinogenicity, mutations further propagate and drastically alter the cancer genomes. Although a subset of driver mutations has been identified and characterized to date, most cancer-r...

Dysregulation of a gene’s function, either due to mutations or impairments in regulatory networks, often triggers pathological states in the affected tissue. Comprehensive mapping of these apparent gene-pathology relationships is an ever daunting task, primarily due to genetic pleiotropy and lack of suitable computational approaches. With the adven...

The genome of a eukaryotic cell is often vulnerable to both intrinsic and extrinsic threats due to its constant exposure to a myriad of heterogeneous chemical compounds. Despite the availability of innate DNA damage repair pathways, some genomic lesions trigger cells for malignant transformation. Accurate prediction of carcinogens is an ever-challe...

The identification and characterization of circulating tumor cells (CTCs) are important for gaining insights into the biology of metastatic cancers, monitoring disease progression, and medical management of the disease. The limiting factor that hinders enrichment of purified CTC populations is their sparse availability, heterogeneity, and altered p...

Inter and intra-tumoral heterogeneity are major stumbling blocks in the treatment of cancer and are responsible for imparting differential drug responses in cancer patients. Recently, the availability of large-scale drug screening datasets has provided an opportunity for predicting appropriate patient-tailored therapies by employing machine learnin...

The molecular mechanisms of olfaction, or the sense of smell, are relatively under-explored compared to other sensory systems, primarily due to its underlying molecular complexity and the limited availability of dedicated predictive computational tools. Odorant receptors allow the detection and discrimination of a myriad of odorant molecules and th...

Age-dependent dysregulation of transcription regulatory machinery triggers modulations in the gene expression levels leading to the decline in cellular fitness. Tracking of these transcripts along the temporal axis in multiple species revealed a spectrum of evolutionarily conserved pathways, such as electron transport chain, translation regulation,...

Dramatic genomic alterations, either inducible or in a pathological state, dismantle the core regulatory networks, leading to the activation of normally silent genes. Despite possessing immense therapeutic potential, accurate detection of these transcripts is an ever-challenging task, as it requires prior knowledge of the physiological gene express...

Single‐cell omics technologies provide biologists with a new dimension for systematically dissecting the underlying complexities within biological systems. These powerful technologies have triggered a wave of rapid development and deployment of new computational tools capable of teasing out critical insights by analysis of large volumes of omics da...

The blueprints for developing organs are preset at the early stages of embryogenesis. Transcriptional and epigenetic mechanisms are proposed to preset developmental trajectories. However, we reveal that the competence for future cardiac fate of human embryonic stem cells (hESCs) is preset in pluripotency by a specialized mRNA translation circuit co...

Systematic delineation of complex biological systems is an ever-challenging and resource-intensive process. Single cell transcriptomics allows us to study cell-to-cell variability in complex tissues at an unprecedented resolution. Accurate modeling of gene expression plays a critical role in the statistical determination of tissue-specific gene exp...

In a preregistered, cross-sectional study, we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0–100...

Machine Learning-based techniques are emerging as state-of-the-art methods in chemoinformatics to selectively, effectively, and speedily identify biologically-relevant molecules from large databases. So far, a multitude of such techniques have been proposed, but unfortunately due to their sparse availability, and the dependency on high-end computat...

In a preregistered, cross-sectional study we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100...

An amendment to this paper has been published and can be accessed via the original article.

Olfactory receptors are primarily known to be expressed in the olfactory epithelium of the nasal cavity and therefore assist in odor perception. With the advent of high‐throughput omics technologies such as tissue microarray or RNA sequencing, a large number of olfactory receptors have been reported to be expressed in the nonolfactory tissues. Alth...

Background Early diagnosis is crucial for effective medical management of cancer patients. Tissue biopsy has been widely used for cancer diagnosis, but its invasive nature limits its application, especially when repeated biopsies are needed. Over the past few years, genomic explorations have led to the discovery of various blood-based biomarkers. T...

Ectopically expressed olfactory receptors (ORs) have been linked with multiple clinically-relevant physiological processes. Previously used tissue-level expression estimation largely shadowed the potential role of ORs due to their overall low expression levels. Even after the introduction of the single-cell transcriptomics, a comprehensive delineat...

A prominent clinical symptom of 2019-novel coronavirus (nCoV) infection is hyposmia/anosmia (decrease or loss of sense of smell), along with general symptoms such as fatigue, shortness of breath, fever and cough. The identity of the cell lineages that underpin the infection-associated loss of olfaction could be critical for the clinical management...

Now published in Chemical Senses doi: 10.1093/chemse/bjaa081. Background: COVID-19 has heterogeneous manifestations, though one of the most common symptoms is a sudden loss of smell (anosmia or hyposmia). We investigated whether olfactory loss is a reliable predictor of COVID-19. Methods: This preregistered, cross-sectional study used a crowdsou...

Background: COVID-19 has heterogeneous manifestations, though one of the most common symptoms is a sudden loss of smell (anosmia or hyposmia). We investigated whether olfactory loss is a reliable predictor of COVID-19. Methods: This preregistered, cross-sectional study used a crowdsourced questionnaire in 23 languages to assess symptoms in individu...

Among the prominent clinical symptoms such as fatigue, shortness of breath, fever, and cough, 2019-nCoV infected individuals often experience hyposmia/anosmia (decrease or loss of sense of smell). Angiotensin I Converting Enzyme 2 (ACE2), a key host receptor has now been established as an important moiety for the entry of 2019-nCoV into the host ce...

Among the prominent clinical symptoms such as fatigue, shortness of breath, fever, and cough, 2019-nCoV infected individuals often experience hyposmia/anosmia (decrease or loss of sense of smell). Angiotensin I Converting Enzyme 2 (ACE2), a key host receptor has now been established as an important moiety for the entry of 2019-nCoV into the host ce...

Cardiac dysfunctions dramatically increase with age. Revealing a currently unknown contributor to cardiac ageing, we report the age-dependent, cardiac-specific accumulation of the lysosphingolipid sphinganine (dihydrosphingosine, DHS) as an evolutionarily conserved hallmark of the aged vertebrate heart. Mechanistically, the DHS-derivative sphingani...

Abstract Long non-coding RNAs (lncRNAs) can act as scaffolds that promote the interaction of proteins, RNA, and DNA. There is increasing evidence of sequence-specific interactions of lncRNAs with DNA via triple-helix (triplex) formation. This process allows lncRNAs to recruit protein complexes to specific genomic regions and regulate gene expressi...

Human protein-coding genes are often accompanied by divergently transcribed non-coding RNAs whose functions, especially in cell fate decisions, are poorly understood. Using an hESC-based cardiac differentiation model, we define a class of divergent lncRNAs, termed yin yang lncRNAs (yylncRNAs), that mirror the cell-type-specific expression pattern o...

Background The sense of smell is unrivaled in terms of molecular complexity of its input channels. Even zebrafish, a model vertebrate system in many research fields including olfaction, possesses several hundred different olfactory receptor genes, organized in four different gene families. For one of these families, the initially discovered odorant...

While the transcriptional network of human embryonic stem cells (hESCs) has been extensively studied, relatively little is known about how post-transcriptional modulations determine hESC function. RNA-binding proteins play central roles in RNA regulation, including translation and turnover. Here we show that the RNA-binding protein CSDE1 (cold shoc...

The death-associated odor cadaverine, generated by bacteria-mediated decarboxylation of lysine, has been described as the principal activator of a particular olfactory receptor in zebrafish, TAAR13c. Low concentrations of cadaverine activated mainly TAAR13c-expressing olfactory sensory neurons, suggesting TAAR13c as an important element of the neur...

Olfaction poses one of the most complex ligand-receptor matching problems in biology due to the unparalleled multitude of odor molecules facing a large number of cognate olfactory receptors. We have recently deorphanized an olfactory receptor, TAAR13c, as a specific receptor for the death-associated odor cadaverine. Here we have modeled the cadaver...

Studies of the two major olfactory organs of rodents, the olfactory mucosa (OM) and the vomeronasal organ (VNO), unraveled the molecular basis of smell in vertebrates. However, some vertebrates lack a VNO. Here we generated and analyzed the olfactory transcriptome of the zebrafish and compared it to the olfactory transcriptomes of mouse to investig...

Studies of the two major olfactory organs of rodents, the olfactory mucosa (OM) and the vomeronasal organ (VNO), unraveled the molecular basis of smell in vertebrates. However, some vertebrates lack a VNO. Here we generated and analyzed the olfactory transcriptome of the zebrafish and compared it to the olfactory transcriptomes of mouse to investig...

Supplementary