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Article ; Online: Protocol to decode the role of transcriptionally active microbes in SARS-CoV-2-positive patients using an RNA-seq-based approach.

Yadav, Aanchal / Devi, Priti / Kumari, Pallawi / Maurya, Ranjeet / Shamim, Uzma / Pandey, Rajesh

STAR protocols

2024 Volume 5, Issue 2, Page(s) 103071

Abstract: The elucidation of the role of microorganisms in human infections has been hindered by difficulties using conventional culture-based techniques. Here, we present a protocol for the investigation of transcriptionally active microbes (TAMs) using an RNA ... ...

Abstract	The elucidation of the role of microorganisms in human infections has been hindered by difficulties using conventional culture-based techniques. Here, we present a protocol for the investigation of transcriptionally active microbes (TAMs) using an RNA sequencing (RNA-seq)-based approach. We describe the steps for RNA isolation, viral genome sequencing, RNA-seq library preparation, and metatranscriptomic and transcriptomic analysis. This protocol permits a comprehensive evaluation of TAMs' contributions to the differential severity of infectious diseases, with a particular focus on diseases such as COVID-19. For complete details on the use and execution of this protocol, please refer to Devi et al.
Language	English
Publishing date	2024-05-19
Publishing country	United States
Document type	Journal Article
ISSN	2666-1667
ISSN (online)	2666-1667
DOI	10.1016/j.xpro.2024.103071
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Article ; Online: From bench to bedside: potential of translational research in COVID-19 and beyond.

Shukla, Nityendra / Shamim, Uzma / Agarwal, Preeti / Pandey, Rajesh / Narayan, Jitendra

Briefings in functional genomics

2023

Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) have been around for more than 3 years now. However, due to constant viral evolution, novel variants are emerging, leaving old treatment protocols ... ...

Abstract	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19) have been around for more than 3 years now. However, due to constant viral evolution, novel variants are emerging, leaving old treatment protocols redundant. As treatment options dwindle, infection rates continue to rise and seasonal infection surges become progressively common across the world, rapid solutions are required. With genomic and proteomic methods generating enormous amounts of data to expand our understanding of SARS-CoV-2 biology, there is an urgent requirement for the development of novel therapeutic methods that can allow translational research to flourish. In this review, we highlight the current state of COVID-19 in the world and the effects of post-infection sequelae. We present the contribution of translational research in COVID-19, with various current and novel therapeutic approaches, including antivirals, monoclonal antibodies and vaccines, as well as alternate treatment methods such as immunomodulators, currently being studied and reiterate the importance of translational research in the development of various strategies to contain COVID-19.
Language	English
Publishing date	2023-11-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2540916-5
ISSN	2041-2657 ; 2041-2649 ; 2041-2647
ISSN (online)	2041-2657
ISSN	2041-2649 ; 2041-2647
DOI	10.1093/bfgp/elad051
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Article: The Clinical Diagnostic Utility of Array CGH in Children with Syndromic Microcephaly.

Goyal, Manisha / Faruq, Mohammed / Gupta, Ashok / Shrivastava, Divya / Shamim, Uzma

Annals of Indian Academy of Neurology

2022 Volume 25, Issue 6, Page(s) 1067–1074

Abstract: Background: A prospective study using array CGH in children with Syndromic microcephaly from a tertiary pediatric healthcare centre in India.: Aim: To identify the copy number variations causative of microcephaly detected through chromosomal array ... ...

Abstract	Background: A prospective study using array CGH in children with Syndromic microcephaly from a tertiary pediatric healthcare centre in India. Aim: To identify the copy number variations causative of microcephaly detected through chromosomal array CGH. Patients and methods: Of the 60 patients, 33 (55%) males and 27 (45%) females who consulted the Rare Disease Clinic at Department of Pediatrics, SMS Medical College, Jaipur, with developmental delay/facial dysmorphism/congenital anomalies in combination with microcephaly were included. Exclusion criteria: Children with acquired or non-genetic causes of microcephaly, craniosynostosis, metabolic diseases, known chromosomal aneuploidy such as trisomy 21, 13, and 18 and abnormal karyotype were excluded. The cohort was analyzed by array CGH in order to identify potentially pathogenic copy number variants (CNVs). Results: Clinically relevant pathogenic or likely pathogenic copy number variations (CNVs) were identified in 20/60 (33.3%) patients, variant of uncertain significance (VOUS) in 4/60 (6.6%) cases and benign CNVs in 3/60 (5%) of total cases. Out of 20 cases with pathogenic CNVs, 12 (60%) patients detected with a deletion, five (25%) patients with duplication and three (15%) patients resulted with a complex chromosomal rearrangement. Twelve cases present CNVs containing genes known to be implicated in microcephaly etiology. Conclusion: This research highlights the contribution of submicroscopic chromosomal changes in the etiology of microcephaly in combination with developmental delay/facial dysmorphism/congenital anomalies (syndromic microcephaly). Our studies provide more insights into the benefits derived by using array CGH analysis in patients with syndromic microcephaly.
Language	English
Publishing date	2022-11-17
Publishing country	India
Document type	Journal Article
ZDB-ID	2240174-X
ISSN	1998-3549 ; 0972-2327
ISSN (online)	1998-3549
ISSN	0972-2327
DOI	10.4103/aian.aian_202_22
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Article ; Online: Longitudinal study across SARS-CoV-2 variants identifies transcriptionally active microbes (TAMs) associated with Delta severity.

Devi, Priti / Kumari, Pallawi / Yadav, Aanchal / Tarai, Bansidhar / Budhiraja, Sandeep / Shamim, Uzma / Pandey, Rajesh

iScience

2023 Volume 26, Issue 10, Page(s) 107779

Abstract: Emergence of new SARS-CoV-2 VOCs jeopardize global vaccine and herd immunity safeguards. VOCs interactions with host microbiota might affect clinical course and outcome. This longitudinal investigation involving Pre-VOC and VOCs (Delta & Omicron) holo- ... ...

Abstract	Emergence of new SARS-CoV-2 VOCs jeopardize global vaccine and herd immunity safeguards. VOCs interactions with host microbiota might affect clinical course and outcome. This longitudinal investigation involving Pre-VOC and VOCs (Delta & Omicron) holo-transcriptome based nasopharyngeal microbiome at taxonomic levels followed by metabolic pathway analysis and integrative host-microbiome interaction. VOCs showed enrichment of
Language	English
Publishing date	2023-08-29
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.107779
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Article: Unraveling the genetic evolution of SARS-CoV-2 Recombinants using mutational dynamics across the different lineages.

Ravi, Varsha / Shamim, Uzma / Khan, Md Abuzar / Swaminathan, Aparna / Mishra, Pallavi / Singh, Rajender / Bharali, Pankaj / Chauhan, Nar Singh / Pandey, Rajesh

Frontiers in medicine

2024 Volume 10, Page(s) 1294699

Abstract: Introduction: Recombination serves as a common strategy employed by RNA viruses for their genetic evolution. Extensive genomic surveillance during the COVID-19 pandemic has reported SARS-CoV-2 Recombinant strains indicating recombination events during ... ...

Abstract	Introduction: Recombination serves as a common strategy employed by RNA viruses for their genetic evolution. Extensive genomic surveillance during the COVID-19 pandemic has reported SARS-CoV-2 Recombinant strains indicating recombination events during the viral evolution. This study introspects the phenomenon of genome recombination by tracing the footprint of prominent lineages of SARS-CoV-2 at different time points in the context of on-going evolution and emergence of Recombinants. Method: Whole genome sequencing was carried out for 2,516 SARS-CoV-2 (discovery cohort) and 1,126 (validation cohort) using nasopharyngeal samples collected between the time period of March 2020 to August 2022, as part of the genomic surveillance program. The sequences were classified according to the different lineages of SARS-CoV-2 prevailing in India at respective time points. Results: Mutational diversity and abundance evaluation across the 12 lineages identified 58 Recombinant sequences as harboring the least number of mutations ( Conclusion: Together, the findings help to understand the evolution and emergence of Recombinants after the Omicron lineages, for sustenance and adaptability, to maintain the epidemic spread of SARS-CoV-2 in the host population already high in immunity levels.
Language	English
Publishing date	2024-01-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2775999-4
ISSN	2296-858X
ISSN	2296-858X
DOI	10.3389/fmed.2023.1294699
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Article ; Online: Transcriptionally active nasopharyngeal commensals and opportunistic microbial dynamics define mild symptoms in the COVID 19 vaccination breakthroughs.

Devi, Priti / Kumari, Pallawi / Yadav, Aanchal / Tarai, Bansidhar / Budhiraja, Sandeep / Shamim, Uzma / Pandey, Rajesh

PLoS pathogens

2023 Volume 19, Issue 2, Page(s) e1011160

Abstract: The development of COVID 19 vaccines as an effort to mitigate the outbreak, has saved millions of lives globally. However, vaccination breakthroughs have continuously challenged the vaccines' effectiveness and provided incentives to explore facets ... ...

Abstract	The development of COVID 19 vaccines as an effort to mitigate the outbreak, has saved millions of lives globally. However, vaccination breakthroughs have continuously challenged the vaccines' effectiveness and provided incentives to explore facets holding potential to alter vaccination-induced immunity and protection from subsequent infection, especially VOCs (Variants Of Concern). We explored the functional dynamics of nasopharyngeal transcriptionally active microbes (TAMs) between vaccination breakthroughs and unvaccinated SARS-CoV-2 infected individuals. Microbial taxonomic communities were differentially altered with skewed enrichment of bacterial class/genera of Firmicutes and Gammaproteobacteria with grossly reduced phylum Bacteroidetes in vaccination breakthrough individuals. The Bacillus genus was abundant in Firmicutes in vaccination breakthrough whereas Prevotella among Bacteroides dominated the unvaccinated. Also, Pseudomonas and Salmonella of Gammaproteobacteria were overrepresented in vaccination breakthrough, whilst unvaccinated showed presence of several genera, Achromobacter, Bordetella, Burkholderia, Neisseria, Hemophilus, Salmonella and Pseudomonas, belonging to Proteobacteria. At species level, the microbiota of vaccination breakthrough exhibited relatively higher abundance of unique commensals, in comparison to potential opportunistic microbes enrichment in unvaccinated patients' microbiota. Functional metabolic pathways like amino acid biosynthesis, sulphate assimilation, fatty acid and beta oxidation, associated with generation of SCFAs (short chain fatty acids), were enriched in vaccination breakthroughs. Majorly, metabolic pathways of LCFAs biosynthesis (long chain fatty acids; oleate, dodecenoate, palmitoleate, gondoate) were found associated with the unvaccinated. Our research highlights that vaccination decreases the microbial diversity in terms of depleting opportunistic pathogens and increasing the preponderance of commensals with respect to unvaccinated patients. Metabolic pathway analysis substantiates the shift in diversity to functionally modulate immune response generation, which may be related to mild clinical manifestations and faster recovery times during vaccination breakthroughs.
MeSH term(s)	Humans ; COVID-19/prevention & control ; COVID-19 Vaccines ; SARS-CoV-2/genetics ; Vaccination ; Bacteroidetes ; Fatty Acids ; Gammaproteobacteria
Chemical Substances	COVID-19 Vaccines ; Fatty Acids
Language	English
Publishing date	2023-02-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1011160
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Article: 6q13q14.3 Microdeletion Syndrome with Severe Hypotonia and Facial Dysmorphism: Genotype-Phenotype Correlation.

Goyal, Manisha / Faruq, Mohammed / Gupta, Ashok / Shrivastava, Divya / Shamim, Uzma

Journal of pediatric genetics

2021 Volume 12, Issue 2, Page(s) 141–143

Abstract: Hypotonia is a symptom of diminished tone of skeletal muscle and can be nongenetic or a part of genetic syndrome. Hypotonia, developmental delay, and facial dysmorphism are nonspecific findings observed in many genetic syndromes mostly in chromosomal ... ...

Abstract	Hypotonia is a symptom of diminished tone of skeletal muscle and can be nongenetic or a part of genetic syndrome. Hypotonia, developmental delay, and facial dysmorphism are nonspecific findings observed in many genetic syndromes mostly in chromosomal microdeletion and duplication. Here we report a case with severe hypotonia and facial dysmorphism, diagnosed with deletion at 6q13q14.3 by array comparative genomic hybridization (CGH) at very early age. Recent genetic diagnostic technologies such as array CGH may enable clinicians to diagnose chromosomal abnormalities earlier and provide appropriate medical management.
Language	English
Publishing date	2021-01-06
Publishing country	Germany
Document type	Case Reports
ISSN	2146-4596
ISSN	2146-4596
DOI	10.1055/s-0040-1721739
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Article ; Online: Integrative genomics important to understand host-pathogen interactions.

Mehta, Priyanka / Swaminathan, Aparna / Yadav, Aanchal / Chattopadhyay, Partha / Shamim, Uzma / Pandey, Rajesh

Briefings in functional genomics

2022 Volume 23, Issue 1, Page(s) 1–14

Abstract: Infectious diseases are the leading cause of morbidity and mortality worldwide. Causative pathogenic microbes readily mutate their genome and lead to outbreaks, challenging the healthcare and the medical support. Understanding how certain symptoms ... ...

Abstract	Infectious diseases are the leading cause of morbidity and mortality worldwide. Causative pathogenic microbes readily mutate their genome and lead to outbreaks, challenging the healthcare and the medical support. Understanding how certain symptoms manifest clinically is integral for therapeutic decisions and vaccination efficacy/protection. Notably, the interaction between infecting pathogens, host response and co-presence of microbes influence the trajectories of disease progression and clinical outcome. The spectrum of observed symptomatic patients (mild, moderate and severe) and the asymptomatic infections highlight the challenges and the potential for understanding the factors driving protection/susceptibility. With the increasing repertoire of high-throughput tools, such as cutting-edge multi-omics profiling and next-generation sequencing, genetic drivers of factors linked to heterogeneous disease presentations can be investigated in tandem. However, such strategies are not without limits in terms of effectively integrating host-pathogen interactions. Nonetheless, an integrative genomics method (for example, RNA sequencing data) for exploring multiple layers of complexity in host-pathogen interactions could be another way to incorporate findings from high-throughput data. We further propose that a Holo-transcriptome-based technique to capture transcriptionally active microbial units can be used to elucidate functional microbiomes. Thus, we provide holistic perspective on investigative methodologies that can harness the same genomic data to investigate multiple seemingly independent but deeply interconnected functional domains of host-pathogen interaction that modulate disease severity and clinical outcomes.
MeSH term(s)	Humans ; Genomics/methods ; Communicable Diseases/genetics ; Host-Pathogen Interactions/genetics ; Transcriptome ; Microbiota
Language	English
Publishing date	2022-08-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2540916-5
ISSN	2041-2657 ; 2041-2649 ; 2041-2647
ISSN (online)	2041-2657
ISSN	2041-2649 ; 2041-2647
DOI	10.1093/bfgp/elac021
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Article ; Online: Intertwined Dysregulation of Ribosomal Proteins and Immune Response Delineates SARS-CoV-2 Vaccination Breakthroughs.

Maurya, Ranjeet / Shamim, Uzma / Mishra, Pallavi / Swaminathan, Aparna / Raina, Aakarshan / Tarai, Bansidhar / Budhiraja, Sandeep / Pandey, Rajesh

Microbiology spectrum

2023 Volume 11, Issue 3, Page(s) e0429222

Abstract: Globally, COVID-19 vaccines have emerged as a boon, especially during the severe pandemic phases to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, saving millions of lives. However, mixed responses to ... ...

Abstract	Globally, COVID-19 vaccines have emerged as a boon, especially during the severe pandemic phases to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, saving millions of lives. However, mixed responses to vaccination with breakthrough challenges provided a rationale to explore the immune responses generated postvaccination, which plausibly alter the subsequent course of infection. In this regard, we comprehensively profiled the nasopharyngeal transcriptomic signature of double-dose-vaccinated individuals with breakthrough infections in comparison to unvaccinated infected persons. The vaccinated individuals demonstrated a gross downregulation of ribosomal proteins along with immune response genes and transcription/translational machinery that methodically modulated the entire innate immune landscape toward immune tolerance, a feature of innate immune memory. This coordinated response was orchestrated through 17 transcription factors captured as differentially expressed in the vaccination breakthroughs, including epigenetic modulators of
MeSH term(s)	Humans ; COVID-19 Vaccines ; SARS-CoV-2/genetics ; COVID-19/prevention & control ; Vaccination ; Immunity, Innate ; Breakthrough Infections
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2023-04-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.04292-22
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Article ; Online: Co-evolution of SARS-CoV-2 variants and host immune response trajectories underlie COVID-19 pandemic to epidemic transition.

Maurya, Ranjeet / Swaminathan, Aparna / Shamim, Uzma / Arora, Smriti / Mishra, Pallavi / Raina, Aakarshan / Ravi, Varsha / Tarai, Bansidhar / Budhiraja, Sandeep / Pandey, Rajesh

iScience

2023 Volume 26, Issue 12, Page(s) 108336

Abstract: COVID-19 pandemic saw emergence of multiple SAR-CoV-2 variants. Exacerbated risk of severe outcome and hospital admissions led us to comprehend differential host-immune kinetics associated with SARS-CoV-2 variants. Longitudinal investigation was ... ...

Abstract	COVID-19 pandemic saw emergence of multiple SAR-CoV-2 variants. Exacerbated risk of severe outcome and hospital admissions led us to comprehend differential host-immune kinetics associated with SARS-CoV-2 variants. Longitudinal investigation was conducted through different time periods of Pre-VOC and VOCs (Delta & Omicron) mapping host transcriptome features. Robust antiviral type-1 interferon response marked Omicron infection, which was largely missing during Pre-VOC and Delta waves. SARS-CoV-2-host protein-protein interactions and docking complexes highlighted N protein to interact with HNRNPA1 in Pre-VOC, demonstrating its functional role for enhanced viral replication. Omicron revealed enhanced binding efficiency of LARP1 to N protein, probably potentiating antiviral effects of LARP1. Differential expression of zinc finger protein genes, especially in Omicron, mechanistically support induction of strong IFN (Interferon) response, thereby strengthening early viral clearance. Study highlights eventual adaptation of host to immune activation patterns that interrupt virus evolution with enhanced immune-evasion mutations and counteraction mechanisms, delimiting the next phase of COVID-19 pandemic.
Language	English
Publishing date	2023-10-27
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.108336
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