Predictive Models of Prenatal Developmental Toxicity from ToxCast High-Throughput Screening Data (original) (raw)
Journal Article
*National Center for Computational Toxicology, Office of Research & Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
1To whom correspondence should be addressed at National Center for Computational Toxicology (B205-01), Office of Research & Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711. Fax: (919) 541-1194. E-mail: [email protected].
Search for other works by this author on:
*National Center for Computational Toxicology, Office of Research & Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
Search for other works by this author on:
*National Center for Computational Toxicology, Office of Research & Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
Search for other works by this author on:
*National Center for Computational Toxicology, Office of Research & Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
Search for other works by this author on:
*National Center for Computational Toxicology, Office of Research & Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
Search for other works by this author on:
†Lockheed Martin, Research Triangle Park, North Carolina 27711
Search for other works by this author on:
‡National Health and Environmental Effects Research Laboratory, Office of Research & Development, U. S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
Search for other works by this author on:
*National Center for Computational Toxicology, Office of Research & Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
Search for other works by this author on:
*National Center for Computational Toxicology, Office of Research & Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
Search for other works by this author on:
*National Center for Computational Toxicology, Office of Research & Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
Search for other works by this author on:
Published:
26 August 2011
Cite
Nisha S. Sipes, Matthew T. Martin, David M. Reif, Nicole C. Kleinstreuer, Richard S. Judson, Amar V. Singh, Kelly J. Chandler, David J. Dix, Robert J. Kavlock, Thomas B. Knudsen, Predictive Models of Prenatal Developmental Toxicity from ToxCast High-Throughput Screening Data, Toxicological Sciences, Volume 124, Issue 1, November 2011, Pages 109–127, https://doi.org/10.1093/toxsci/kfr220
Close
Navbar Search Filter Mobile Enter search term Search
Abstract
Environmental Protection Agency’s ToxCast project is profiling the in vitro bioactivity of chemicals to assess pathway-level and cell-based signatures that correlate with observed in vivo toxicity. We hypothesized that developmental toxicity in guideline animal studies captured in the ToxRefDB database would correlate with cell-based and cell-free in vitro high-throughput screening (HTS) data to reveal meaningful mechanistic relationships and provide models identifying chemicals with the potential to cause developmental toxicity. To test this hypothesis, we built statistical associations based on HTS and in vivo developmental toxicity data from ToxRefDB. Univariate associations were used to filter HTS assays based on statistical correlation with distinct in vivo endpoint. This revealed 423 total associations with distinctly different patterns for rat (301 associations) and rabbit (122 associations) across multiple HTS assay platforms. From these associations, linear discriminant analysis with cross-validation was used to build the models. Species-specific models of predicted developmental toxicity revealed strong balanced accuracy (> 70%) and unique correlations between assay targets such as transforming growth factor beta, retinoic acid receptor, and G-protein–coupled receptor signaling in the rat and inflammatory signals, such as interleukins (IL) (IL1a and IL8) and chemokines (CCL2), in the rabbit. Species-specific toxicity endpoints were associated with one another through common Gene Ontology biological processes, such as cleft palate to urogenital defects through placenta and embryonic development. This work indicates the utility of HTS assays for developing pathway-level models predictive of developmental toxicity.
Published by Oxford University Press on behalf of the Society of Toxicology 2011.
Topic:
- oryctolagus cuniculus
- prenatal care
- rats
- developmental toxicity
- surrogate endpoints
- high-throughput screening methods
You do not currently have access to this article.
I agree to the terms and conditions. You must accept the terms and conditions.
Submit a comment
Name
Affiliations
Comment title
Comment
You have entered an invalid code
Thank you for submitting a comment on this article. Your comment will be reviewed and published at the journal's discretion. Please check for further notifications by email.
Personal account
- Sign in with email/username & password
- Get email alerts
- Save searches
- Purchase content
- Activate your purchase/trial code
- Add your ORCID iD
Get help with access
Institutional access
Access to content on Oxford Academic is often provided through institutional subscriptions and purchases. If you are a member of an institution with an active account, you may be able to access content in one of the following ways:
IP based access
Typically, access is provided across an institutional network to a range of IP addresses. This authentication occurs automatically, and it is not possible to sign out of an IP authenticated account.
Sign in through your institution
Choose this option to get remote access when outside your institution. Shibboleth/Open Athens technology is used to provide single sign-on between your institution's website and Oxford Academic.
- Click Sign in through your institution.
- Select your institution from the list provided, which will take you to your institution's website to sign in.
- When on the institution site, please use the credentials provided by your institution. Do not use an Oxford Academic personal account.
- Following successful sign in, you will be returned to Oxford Academic.
If your institution is not listed or you cannot sign in to your institution's website, please contact your librarian or administrator.
Sign in with a library card
Enter your library card number to sign in. If you cannot sign in, please contact your librarian.
Society Members
Society member access to a journal is achieved in one of the following ways:
Sign in through society site
Many societies offer single sign-on between the society website and Oxford Academic. If you see "Sign in through society site" in the sign in pane within a journal:
- Click Sign in through society site.
- When on the society site, please use the credentials provided by that society. Do not use an Oxford Academic personal account.
- Following successful sign in, you will be returned to Oxford Academic.
If you do not have a society account or have forgotten your username or password, please contact your society.
Sign in using a personal account
Some societies use Oxford Academic personal accounts to provide access to their members. See below.
Personal account
A personal account can be used to get email alerts, save searches, purchase content, and activate subscriptions.
Some societies use Oxford Academic personal accounts to provide access to their members.
Viewing your signed in accounts
Click the account icon in the top right to:
- View your signed in personal account and access account management features.
- View the institutional accounts that are providing access.
Signed in but can't access content
Oxford Academic is home to a wide variety of products. The institutional subscription may not cover the content that you are trying to access. If you believe you should have access to that content, please contact your librarian.
Institutional account management
For librarians and administrators, your personal account also provides access to institutional account management. Here you will find options to view and activate subscriptions, manage institutional settings and access options, access usage statistics, and more.
Purchase
Short-term Access
To purchase short-term access, please sign in to your personal account above.
Don't already have a personal account? Register
Predictive Models of Prenatal Developmental Toxicity from ToxCast High-Throughput Screening Data - 24 Hours access
EUR €53.00
GBP £44.00
USD $58.00
Rental
This article is also available for rental through DeepDyve.