Dataset Information

Discovering Venom-Derived Drug Candidates Using Differential Gene Expression.

ABSTRACT: Venoms are a diverse and complex group of natural toxins that have been adapted to treat many types of human disease, but rigorous computational approaches for discovering new therapeutic activities are scarce. We have designed and validated a new platform-named VenomSeq-to systematically identify putative associations between venoms and drugs/diseases via high-throughput transcriptomics and perturbational differential gene expression analysis. In this study, we describe the architecture of VenomSeq and its evaluation using the crude venoms from 25 diverse animal species and 9 purified teretoxin peptides. By integrating comparisons to public repositories of differential expression, associations between regulatory networks and disease, and existing knowledge of venom activity, we provide a number of new therapeutic hypotheses linking venoms to human diseases supported by multiple layers of preliminary evidence.

SUBMITTER: Romano JD

PROVIDER: S-EPMC10467105 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Discovering Venom-Derived Drug Candidates Using Differential Gene Expression.

Romano Joseph D JD Li Hai H Napolitano Tanya T Realubit Ronald R Karan Charles C Holford Mandë M Tatonetti Nicholas P NP

Toxins 20230709 7

Venoms are a diverse and complex group of natural toxins that have been adapted to treat many types of human disease, but rigorous computational approaches for discovering new therapeutic activities are scarce. We have designed and validated a new platform-named VenomSeq-to systematically identify putative associations between venoms and drugs/diseases via high-throughput transcriptomics and perturbational differential gene expression analysis. In this study, we describe the architecture of Veno ...[more]

PMID: 37505720

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Project description:Identifying similarities between patterns of differential gene expression provides an opportunity to identify similarities between the experimental and biological conditions that give rise to these gene expression alterations. The growing volume of gene expression data in open data repositories such as the NCBI Gene Expression Omnibus (GEO) presents an opportunity to identify these gene expression similarities on a large scale across a diverse collection of datasets. We have developed a fast, pattern-based computational approach, named openSESAME (Search of Expression Signatures Across Many Experiments), that identifies datasets enriched in samples that display coordinate differential expression of a query signature. Importantly, openSESAME performs this search without prior knowledge of the phenotypic or experimental groups in the datasets being searched. This allows openSESAME to identify perturbations of gene expression that are due to phenotypic attributes that may not have been described in the sample annotation included in the repository. : To demonstrate the utility of openSESAME, we used gene expression signatures of two biological perturbations to query a set of 75,164 human expression profiles that were generated using Affymetrix microarrays and deposited in GEO. The first query, using a signature of estradiol treatment, identified experiments in which estrogen signaling was perturbed and also identified differences in estrogen signaling between estrogen receptor-positive and -negative breast cancers. The second query, which used a signature of silencing of the transcription factor p63 (a key regulator of epidermal differentiation), identified datasets related to stratified squamous epithelia or epidermal diseases such as melanoma.openSESAME is a tool for leveraging the growing body of publicly available microarray data to discover relationships between different biological states based on common patterns of differential gene expression. These relationships may serve to generate hypotheses about the causes and consequences of specific patterns of observed differential gene expression.

Project description:BackgroundNetwork-based approaches for the analysis of large-scale genomics data have become well established. Biological networks provide a knowledge scaffold against which the patterns and dynamics of 'omics' data can be interpreted. The background information required for the construction of such networks is often dispersed across a multitude of knowledge bases in a variety of formats. The seamless integration of this information is one of the main challenges in bioinformatics. The Semantic Web offers powerful technologies for the assembly of integrated knowledge bases that are computationally comprehensible, thereby providing a potentially powerful resource for constructing biological networks and network-based analysis.ResultsWe have developed the Gene eXpression Knowledge Base (GeXKB), a semantic web technology based resource that contains integrated knowledge about gene expression regulation. To affirm the utility of GeXKB we demonstrate how this resource can be exploited for the identification of candidate regulatory network proteins. We present four use cases that were designed from a biological perspective in order to find candidate members relevant for the gastrin hormone signaling network model. We show how a combination of specific query definitions and additional selection criteria derived from gene expression data and prior knowledge concerning candidate proteins can be used to retrieve a set of proteins that constitute valid candidates for regulatory network extensions.ConclusionsSemantic web technologies provide the means for processing and integrating various heterogeneous information sources. The GeXKB offers biologists such an integrated knowledge resource, allowing them to address complex biological questions pertaining to gene expression. This work illustrates how GeXKB can be used in combination with gene expression results and literature information to identify new potential candidates that may be considered for extending a gene regulatory network.

Dataset Information

Discovering Venom-Derived Drug Candidates Using Differential Gene Expression.

Publications

Discovering Venom-Derived Drug Candidates Using Differential Gene Expression.

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