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. 2024 Sep 19:249:10279.
doi: 10.3389/ebm.2024.10279. eCollection 2024.

Development of a comprehensive open access "molecules with androgenic activity resource (MAAR)" to facilitate risk assessment of chemicals

Fan Dong  1 , Barry Hardy  2 , Jie Liu  1 , Tomaz Mohoric  2 , Wenjing Guo  1 , Thomas Exner  2 , Weida Tong  1 , Joh Dohler  2 , Daniel Bachler  2 , Huixiao Hong  1
Affiliations

Development of a comprehensive open access "molecules with androgenic activity resource (MAAR)" to facilitate risk assessment of chemicals

Fan Dong et al. Exp Biol Med (Maywood). .

Abstract

The increasing prevalence of endocrine-disrupting chemicals (EDCs) and their potential adverse effects on human health underscore the necessity for robust tools to assess and manage associated risks. The androgen receptor (AR) is a critical component of the endocrine system, playing a pivotal role in mediating the biological effects of androgens, which are male sex hormones. Exposure to androgen-disrupting chemicals during critical periods of development, such as fetal development or puberty, may result in adverse effects on reproductive health, including altered sexual differentiation, impaired fertility, and an increased risk of reproductive disorders. Therefore, androgenic activity data is critical for chemical risk assessment. A large amount of androgenic data has been generated using various experimental protocols. Moreover, the data are reported in different formats and in diverse sources. To facilitate utilization of androgenic activity data in chemical risk assessment, the Molecules with Androgenic Activity Resource (MAAR) was developed. MAAR is the first open-access platform designed to streamline and enhance the risk assessment of chemicals with androgenic activity. MAAR's development involved the integration of diverse data sources, including data from public databases and mining literature, to establish a reliable and versatile repository. The platform employs a user-friendly interface, enabling efficient navigation and extraction of pertinent information. MAAR is poised to advance chemical risk assessment by offering unprecedented access to information crucial for evaluating the androgenic potential of a wide array of chemicals. The open-access nature of MAAR promotes transparency and collaboration, fostering a collective effort to address the challenges posed by androgenic EDCs.

Keywords: androgen receptor; chemicals; database; open access; risk assessment.

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Conflict of interest statement

Authors BH, TM, TE, JD, and DB were employed by Edelweiss Connect Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Androgenic Activity Data Collection and Curation. Data collection sources including ChemBL, PubChem, BindingDB, EDKB, CTD, Toxcast. After data pre-processing steps, Androgenic Activity Data are curated into four categories: Activity Data information, Reference information, Assay information, Chemical information.
FIGURE 2
FIGURE 2
Database schema.
FIGURE 3
FIGURE 3
Distribution of androgenic activity data for the same chemical. Each bar represents the number of chemicals. X-axis indicates the number of data records for the same chemicals. The chemicals with 41–50 data records were grouped into the bar with x-axis value 41 and the chemicals with more than 50 data were grouped in the last bar with x-axis value 42.
FIGURE 4
FIGURE 4
Ratio of active data among 4 binding assay data for 127 chemicals. Each bar represents the number of chemicals. X-axis indicates the ratio of active data.
FIGURE 5
FIGURE 5
User interface of the web resource.
FIGURE 6
FIGURE 6
JSON response from the database.
FIGURE 7
FIGURE 7
Two sections of the AADB Observable notebook: user interface for entering the input parameters (left) and visualization of filtered results (right).
FIGURE 8
FIGURE 8
Chemical spaces of MAAR and Tox21. Compounds in MAAR and Tox21 are plotted as blue and red circles, respectively. The x-, y-, and z-axes give the first three principal components.
See this image and copyright information in PMC

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