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Article ; Online: Advancing discovery in hearing research via biologist-friendly access to multi-omic data.

Hertzano, Ronna / Mahurkar, Anup

2022 Volume 141, Issue 3-4, Page(s) 319–322

Abstract: High-throughput cell type-specific multi-omic analyses have advanced our understanding of inner ear biology in an unprecedented way. The full benefit of these data, however, is reached from their re-use. Successful re-use of data requires identifying the ...

Abstract	High-throughput cell type-specific multi-omic analyses have advanced our understanding of inner ear biology in an unprecedented way. The full benefit of these data, however, is reached from their re-use. Successful re-use of data requires identifying the natural users and ensuring proper data democratization and federation for their seamless and meaningful access. Here we discuss universal challenges in access and re-use of multi-omic data, possible solutions, and introduce the gEAR (the gene Expression Analysis Resource, umgear.org)-a tool for multi-omic data visualization, sharing and access for the ear field.
MeSH term(s)	Genomics ; Hearing ; Humans
Language	English
Publishing date	2022-03-02
Publishing country	Germany
Document type	Journal Article
ZDB-ID	223009-4
ISSN	1432-1203 ; 0340-6717
ISSN (online)	1432-1203
ISSN	0340-6717
DOI	10.1007/s00439-022-02445-w
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Article ; Online: Reprogramming Chromosome Ends by Functional Histone Acetylation.

Meltzer, W Alex / Gupta, Aditi / Lin, Phyo Nay / Brown, Robert A / Benyamien-Roufaeil, Daniel S / Khatri, Raju / Mahurkar, Anup A / Song, Yang / Taylor, Rodney J / Zalzman, Michal

International journal of molecular sciences

2024 Volume 25, Issue 7

Abstract: Cancers harness embryonic programs to evade aging and promote survival. Normally, sequences at chromosome ends called telomeres shorten with cell division, serving as a countdown clock to limit cell replication. Therefore, a crucial aspect of cancerous ... ...

Abstract	Cancers harness embryonic programs to evade aging and promote survival. Normally, sequences at chromosome ends called telomeres shorten with cell division, serving as a countdown clock to limit cell replication. Therefore, a crucial aspect of cancerous transformation is avoiding replicative aging by activation of telomere repair programs. Mouse embryonic stem cells (mESCs) activate a transient expression of the gene
MeSH term(s)	Animals ; Mice ; Humans ; Histones ; Acetylation ; Telomere/genetics ; Chromatin/genetics ; Aging
Chemical Substances	Histones ; Chromatin
Language	English
Publishing date	2024-03-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25073898
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Article ; Online: Peripheral blood transcriptomic profiling of molecular mechanisms commonly regulated by binge drinking and placebo effects.

Shetty, Amol Carl / Sivinski, John / Cornell, Jessica / McCracken, Carrie / Sadzewicz, Lisa / Mahurkar, Anup / Wang, Xing-Qun / Colloca, Luana / Lin, Weihong / Pilli, Nageswara / Kane, Maureen A / Seneviratne, Chamindi

Scientific reports

2024 Volume 14, Issue 1, Page(s) 10733

Abstract: Molecular responses to alcohol consumption are dynamic, context-dependent, and arise from a complex interplay of biological and external factors. While many have studied genetic risk associated with drinking patterns, comprehensive studies identifying ... ...

Abstract	Molecular responses to alcohol consumption are dynamic, context-dependent, and arise from a complex interplay of biological and external factors. While many have studied genetic risk associated with drinking patterns, comprehensive studies identifying dynamic responses to pharmacologic and psychological/placebo effects underlying binge drinking are lacking. We investigated transcriptome-wide response to binge, medium, and placebo alcohol consumption by 17 healthy heavy social drinkers enrolled in a controlled, in-house, longitudinal study of up to 12 days. Using RNA-seq, we identified 251 and 13 differentially expressed genes (DEGs) in response to binge drinking and placebo, respectively. Eleven protein-coding DEGs had very large effect sizes in response to binge drinking (Cohen's d > 1). Furthermore, binge dose significantly impacted the Cytokine-cytokine receptor interaction pathway (KEGG: hsa04060) across all experimental sequences. Placebo also impacted hsa04060, but only when administered following regular alcohol drinking sessions. Similarly, medium-dose and placebo commonly impacted KEGG pathways of Systemic lupus erythematosus, Neutrophil extracellular trap formation, and Alcoholism based on the sequence of drinking sessions. These findings together indicate the "dose-extending effects" of placebo at a molecular level. Furthermore, besides supporting alcohol dose-specific molecular changes, results suggest that the placebo effects may induce molecular responses within the same pathways regulated by alcohol.
MeSH term(s)	Humans ; Binge Drinking/blood ; Binge Drinking/genetics ; Male ; Placebo Effect ; Female ; Adult ; Transcriptome ; Gene Expression Profiling ; Young Adult ; Ethanol ; Longitudinal Studies ; Gene Expression Regulation/drug effects
Chemical Substances	Ethanol (3K9958V90M)
Language	English
Publishing date	2024-05-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-56900-x
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Article: Peripheral blood transcriptomic profiling indicates molecular mechanisms commonly regulated by binge-drinking and placebo-effects.

Shetty, Amol Carl / Sivinski, John / Cornell, Jessica / Sadzewicz, Lisa / Mahurkar, Anup / Wang, Xing-Qun / Colloca, Luana / Lin, Weihong / Kane, Maureen A / Seneviratne, Chamindi

medRxiv : the preprint server for health sciences

2023

Abstract: Molecular changes associated with alcohol consumption arise from complex interactions between pharmacological effects of alcohol, psychological/placebo context surrounding drinking, and other environmental and biological factors. The goal of this study ... ...

Abstract	Molecular changes associated with alcohol consumption arise from complex interactions between pharmacological effects of alcohol, psychological/placebo context surrounding drinking, and other environmental and biological factors. The goal of this study was to tease apart molecular mechanisms regulated by pharmacological effects of alcohol - particularly at binge-drinking, from underlying placebo effects. Transcriptome-wide RNA-seq analyses were performed on peripheral blood samples collected from healthy heavy social drinkers (N=16) enrolled in a 12-day randomized, double-blind, cross-over human laboratory trial testing three alcohol doses: Placebo, moderate (0.05g/kg (men), 0.04g/kg (women)), and binge (1g/kg (men), 0.9g/kg (women)), administered in three 4-day experiments, separated by minimum of 7-day washout periods. Effects of beverage doses on the normalized gene expression counts were analyzed within each experiment compared to its own baseline using paired-t-tests. Differential expression of genes (DEGs) across experimental sequences in which each beverage dose was administered, as well as responsiveness to regular alcohol compared to placebo (i.e., pharmacological effects), were analyzed using generalized linear mixed-effects models. The 10% False discovery rate-adjusted DEGs varied across experimental sequences in response to all three beverage doses. We identified and validated 22 protein coding DEGs potentially responsive to pharmacological effects of binge and medium doses, of which 11 were selectively responsive to binge dose. Binge-dose significantly impacted the Cytokine-cytokine receptor interaction pathway (KEGG: hsa04060) across all experimental-sequences that it was administered in, and during dose-extending placebo. Medium dose and placebo impacted pathways hsa05322, hsa04613, and hsa05034, in the first two and last experimental sequences, respectively. In summary, our findings add novel, and confirm previously reported data supporting dose-dependent effects of alcohol on molecular mechanisms and suggest that the placebo effects may induce molecular responses within the same pathways regulated by alcohol. Innovative study designs are required to validate molecular correlates of placebo effects underlying drinking.
Language	English
Publishing date	2023-03-24
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.21.23287501
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Article: in silico

bioRxiv : the preprint server for biology

2024

Abstract: The rising quality and amount of multi-omic data across biomedical science demands that we build innovative solutions to harness their collective discovery potential. From publicly available repositories, we have assembled and curated a compendium of ... ...

Abstract	The rising quality and amount of multi-omic data across biomedical science demands that we build innovative solutions to harness their collective discovery potential. From publicly available repositories, we have assembled and curated a compendium of gene-level transcriptomic data focused on mammalian excitatory neurogenesis in the neocortex. This collection is open for exploration by both computational and cell biologists at nemoanalytics.org, and this report forms a demonstration of its utility. Applying our novel structured joint decomposition approach to mouse, macaque and human data from the collection, we define transcriptome dynamics that are conserved across mammalian excitatory neurogenesis and which map onto the genetics of human brain structure and disease. Leveraging additional data within NeMO Analytics via projection methods, we chart the dynamics of these fundamental molecular elements of neurogenesis across developmental time and space and into postnatal life. Reversing the direction of our investigation, we use transcriptomic data from laminar-specific dissection of adult human neocortex to define molecular signatures specific to excitatory neuronal cell types resident in individual layers of the mature neocortex, and trace their emergence across development. We show that while many lineage defining transcription factors are most highly expressed at early fetal ages, the laminar neuronal identities which they drive take years to decades to reach full maturity. Finally, we interrogated data from stem-cell derived cerebral organoid systems demonstrating that many fundamental elements of
Language	English
Publishing date	2024-02-28
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.26.581612
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Article: Best practices on the differential expression analysis of multi-species RNA-seq

Chung, Matthew / Bruno, Vincent M / Rasko, David A / Cuomo, Christina A / Muñoz, José F / Livny, Jonathan / Shetty, Amol C / Mahurkar, Anup / Dunning Hotopp, Julie C

Genome biology. 2021 Dec., v. 22, no. 1

2021

Abstract: Advances in transcriptome sequencing allow for simultaneous interrogation of differentially expressed genes from multiple species originating from a single RNA sample, termed dual or multi-species transcriptomics. Compared to single-species differential ... ...

Abstract	Advances in transcriptome sequencing allow for simultaneous interrogation of differentially expressed genes from multiple species originating from a single RNA sample, termed dual or multi-species transcriptomics. Compared to single-species differential expression analysis, the design of multi-species differential expression experiments must account for the relative abundances of each organism of interest within the sample, often requiring enrichment methods and yielding differences in total read counts across samples. The analysis of multi-species transcriptomics datasets requires modifications to the alignment, quantification, and downstream analysis steps compared to the single-species analysis pipelines. We describe best practices for multi-species transcriptomics and differential gene expression.
Keywords	RNA ; data collection ; gene expression regulation ; sequence analysis ; transcriptome ; transcriptomics
Language	English
Dates of publication	2021-12
Size	p. 121.
Publishing place	BioMed Central
Document type	Article
Note	Review
ZDB-ID	2040529-7
ISSN	1474-760X
ISSN	1474-760X
DOI	10.1186/s13059-021-02337-8
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Article: Matrix and analysis metadata standards (MAMS) to facilitate harmonization and reproducibility of single-cell data.

Wang, Yichen / Sarfraz, Irzam / Teh, Wei Kheng / Sokolov, Artem / Herb, Brian R / Creasy, Heather H / Virshup, Isaac / Dries, Ruben / Degatano, Kylee / Mahurkar, Anup / Schnell, Daniel J / Madrigal, Pedro / Hilton, Jason / Gehlenborg, Nils / Tickle, Timothy / Campbell, Joshua D

bioRxiv : the preprint server for biology

2023

Abstract: A large number of genomic and imaging datasets are being produced by consortia that seek to characterize healthy and disease tissues at single-cell resolution. While much effort has been devoted to capturing information related to biospecimen information ...

Abstract	A large number of genomic and imaging datasets are being produced by consortia that seek to characterize healthy and disease tissues at single-cell resolution. While much effort has been devoted to capturing information related to biospecimen information and experimental procedures, the metadata standards that describe data matrices and the analysis workflows that produced them are relatively lacking. Detailed metadata schema related to data analysis are needed to facilitate sharing and interoperability across groups and to promote data provenance for reproducibility. To address this need, we developed the Matrix and Analysis Metadata Standards (MAMS) to serve as a resource for data coordinating centers and tool developers. We first curated several simple and complex "use cases" to characterize the types of feature-observation matrices (FOMs), annotations, and analysis metadata produced in different workflows. Based on these use cases, metadata fields were defined to describe the data contained within each matrix including those related to processing, modality, and subsets. Suggested terms were created for the majority of fields to aid in harmonization of metadata terms across groups. Additional provenance metadata fields were also defined to describe the software and workflows that produced each FOM. Finally, we developed a simple list-like schema that can be used to store MAMS information and implemented in multiple formats. Overall, MAMS can be used as a guide to harmonize analysis-related metadata which will ultimately facilitate integration of datasets across tools and consortia. MAMS specifications, use cases, and examples can be found at https://github.com/single-cell-mams/mams/.
Language	English
Publishing date	2023-03-07
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.06.531314
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Article ; Online: Translatome changes in acute myeloid leukemia cells post exposure to pegcrisantaspase and venetoclax.

Kapadia, Bandish / Shetty, Amol C / Bollino, Dominique / Bhandary, Binny / Lapidus, Rena G / Mahmood, Kanwal / Mahurkar, Anup / Gartenhaus, Ronald B / Eckert, Richard L / Emadi, Ashkan

Experimental hematology

2022 Volume 108, Page(s) 55–63

Abstract: The clinical outcomes of patients with acute myeloid leukemia (AML) treated with available therapy remain unsatisfactory. We recently reported that the BCL-2 inhibitor venetoclax synergizes with pegcrisantaspase (Ven-PegC) and exhibits remarkable in vivo ...

Abstract	The clinical outcomes of patients with acute myeloid leukemia (AML) treated with available therapy remain unsatisfactory. We recently reported that the BCL-2 inhibitor venetoclax synergizes with pegcrisantaspase (Ven-PegC) and exhibits remarkable in vivo efficacy in a preclinical model of AML with complex karyotype. The Ven-PegC combination blocks synthesis of proteins in AML cells by inhibiting cap-dependent translation of mRNA. To further explore the impact of Ven-PegC on protein translation, we used polysome profiling and high-throughput RNA sequencing to characterize Ven-PegC-dependent changes to the translatome. Here we report that the translation of five mRNAs, including two microRNAs, one rRNA, and two mitochondrial genes, was altered after exposure to all three treatments (Ven, PegC, and Ven-PegC). We focused our translatome validation studies on six additional genes related to translational efficiency that were modified by Ven-PegC. Notably, Ven-PegC treatment increased the RNA translation and protein levels of Tribbles homologue 3 (TRIB3), eukaryotic translation initiation factor 3 subunit C (eIF3C), doublesex and mab-3-related transcription factor 1 (DMRT1), and salt-inducible kinase 1 (SIK1). We validated the observed changes in gene/protein expression in vitro and confirmed our cell line-based studies in the bone marrow of an AML patient-derived xenograft model after Ven-PegC treatment. These results support examining alterations in the translatome post chemotherapy to offer insight into the drug's mechanism of action and to inform future therapeutic decisions.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use ; Humans ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; Sulfonamides/pharmacology ; Sulfonamides/therapeutic use
Chemical Substances	Bridged Bicyclo Compounds, Heterocyclic ; Sulfonamides ; venetoclax (N54AIC43PW)
Language	English
Publishing date	2022-01-31
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	185107-x
ISSN	1873-2399 ; 0531-5573 ; 0301-472X
ISSN (online)	1873-2399
ISSN	0531-5573 ; 0301-472X
DOI	10.1016/j.exphem.2022.01.006
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Article ; Online: Interactive exploratory data analysis of Integrative Human Microbiome Project data using Metaviz.

Wagner, Justin / Kancherla, Jayaram / Braccia, Domenick / Matsumara, James / Felix, Victor / Crabtree, Jonathan / Mahurkar, Anup / Corrada Bravo, Héctor

F1000Research

2020 Volume 9, Page(s) 601

Abstract: The rich data produced by the second phase of the Human Microbiome Project (iHMP) offers a unique opportunity to test hypotheses that interactions between microbial communities and a human host might impact an individual's health or disease status. In ... ...

Abstract	The rich data produced by the second phase of the Human Microbiome Project (iHMP) offers a unique opportunity to test hypotheses that interactions between microbial communities and a human host might impact an individual's health or disease status. In this work we describe infrastructure that integrates Metaviz, an interactive microbiome data analysis and visualization tool, with the iHMP Data Coordination Center web portal and the
MeSH term(s)	Data Analysis ; Data Interpretation, Statistical ; Humans ; Microbiota ; Research Design
Language	English
Publishing date	2020-06-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2699932-8
ISSN	2046-1402 ; 2046-1402
ISSN (online)	2046-1402
ISSN	2046-1402
DOI	10.12688/f1000research.24345.2
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Article ; Online: The miRNA Expression Profile of Experimental Autoimmune Encephalomyelitis Reveals Novel Potential Disease Biomarkers.

Venkatesha, Shivaprasad H / Dudics, Steven / Song, Yang / Mahurkar, Anup / Moudgil, Kamal D

International journal of molecular sciences

2018 Volume 19, Issue 12

Abstract: Multiple sclerosis (MS) is a debilitating autoimmune disease affecting over 2.3 million people worldwide, and it is characterized by inflammation and demyelination of nerve cells. The currently available biomarkers for the diagnosis and management of MS ... ...

Abstract	Multiple sclerosis (MS) is a debilitating autoimmune disease affecting over 2.3 million people worldwide, and it is characterized by inflammation and demyelination of nerve cells. The currently available biomarkers for the diagnosis and management of MS have inherent limitations, therefore, additional new biomarkers are needed. We studied the microRNA (miRNA) profile of splenocytes of mice having experimental autoimmune encephalomyelitis (EAE), a model of human MS. A miRNA-microarray analysis revealed increased expression of nine miRNAs (let-7e, miR-23b, miR-31, miR-99b, miR-125a, miR-146b, miR-155, miR-193b, and miR-221) following EAE development. Interestingly, serum levels of miR-99b, miR-125a, and miR-146b were significantly higher in EAE mice compared to normal mice. Bioinformatics analysis revealed the experimentally validated as well as predicted gene targets of specific miRNAs that are important for disease progression in MS. Specifically, we observed inverse correlation in the levels of miR-99b versus
MeSH term(s)	Animals ; Biomarkers/metabolism ; Cell Differentiation/genetics ; Cell Differentiation/physiology ; Encephalomyelitis, Autoimmune, Experimental/genetics ; Encephalomyelitis, Autoimmune, Experimental/metabolism ; Humans ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Multiple Sclerosis/genetics ; Multiple Sclerosis/metabolism ; Signal Transduction/genetics ; Signal Transduction/physiology
Chemical Substances	Biomarkers ; MicroRNAs
Language	English
Publishing date	2018-12-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms19123990
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