SOW_RFP_NIHES2015048.pdf

Statement of Work for

Bioinformatics Support for the National Institute of Environmental Health Sciences (NIEHS) in the Division of Intramural Research (DIR) and the Division of the National Toxicology Program (DNTP)

March 9, 2016

The National Institute of Environmental Health Sciences (NIEHS) (http://www.niehs.nih.gov/index.cfm), located in Research Triangle Park, North Carolina, is one of 27 research institutes and centers that comprise the National Institutes of Health (NIH) (http://www.nih.gov/). The mission of the NIEHS is to reduce the burden of human illness and disability by understanding how the environment influences the development and progression of human disease. In-house research at NIEHS is conducted by investigators in the Division of Intramural Research (DIR) and the Division of the National Toxicology Program (DNTP). DIR researchers investigate the role of environmental agents in human disease and dysfunction, underlying mechanisms of environmentally-associated diseases, and intervention/prevention strategies to reduce the effects of exposures to environmental agents. Specific DIR research topics are available at http://www.niehs.nih.gov/research/atniehs/dir/index.cfm. The National Toxicology Program (NTP) (http://ntp.niehs.nih.gov and http://www.niehs.nih.gov/research/atniehs/dntp/index.cfm) is a federal, interagency program, headquartered at the NIEHS, whose goal is to provide information about potentially hazardous agents by taking advantage of technological advances in molecular biology and computer science.

NIEHS researchers conduct studies that produce large amounts of data, varying in size and complexity. Fields of scientific study are diverse and include toxicology, transcriptomics, genomics and high throughput screening (HTS) activities which generate large amounts of data that require support and assistance to provide NIEHS scientists with innovative bioinformatics analysis and adapt new software tools for these analyses. While members of the Biostatistics and Computational Biology Branch are able to provide some statistical support to the Institute, there are more studies than can be handled by existing staff. Thus, a bioinformatics contract is needed to provide support for the magnitude and range of data and bioinformatics analysis for the studies conducted at NIEHS.

A. General Requirements

1. Independently, and not as an agent of the government, the contractor shall provide all the necessary services, qualified personnel, material, equipment, and facilities not otherwise provided by the Government as needed to assist in the performance of the bioinformatics, data mining and computational activities described herein.

http://www.niehs.nih.gov/index.cfm http://www.nih.gov/ http://www.niehs.nih.gov/research/atniehs/dir/index.cfm http://ntp.niehs.nih.gov/ http://www.niehs.nih.gov/research/atniehs/dntp/index.cfm

2. As directed by the COR, the contractor shall consult with NIEHS staff regarding various bioinformatics/data mining activities and shall report results of data analyses to NIEHS committees and workgroups as needed.

3. The contractor shall apply for permission from the appropriate NTP committee for access to the CEBS (Chemical Effects on Biological Systems) database in order to download and upload raw data as directed by the COR. Data files shall be in standard formats so that computer compatibility will not be an issue.

4. The contractor shall stay current in new trends and developments in bioinformatics, data/text mining and computational methods and advise the COR regarding possible utilization of these procedures. Since bioinformatics is broad and is cross-disciplinary, keeping current may involve multiple research areas of biology including genomics, gene expression, epigenomics, stem cell biology and many other areas. Activities will be attending seminars, participating in appropriate workshops and meetings, reading scientific literature and authorship in papers published in peer-reviewed literature.

5. There shall be frequent personal interaction between the contractor and the COR or other designated NIEHS researchers since there are often timely issues to resolve on experimental design, data analysis, and interpretation of data analyses that require in-depth discussion. Research areas include general toxicology, structure activity relationships of chemicals, toxicogenomics, genomics, gene expression, high throughput screening, NextGen sequencing, and data extraction from diverse literature sources. Such onsite personal interactions of the contractor with NTP and DIR researchers usually occur with short notice (within 1 hour). Moreover, the contractor shall need to attend various onsite NIEHS meetings as directed by the COR. Therefore, the Contractor shall maintain an operational office near Research Triangle Park, North Carolina, 27709 so as to provide a one-hour response time.

6. The actual number of projects conducted for which analyses are required may be higher or lower than indicated below depending upon the needs of the government and available funding.

The Contractor shall ensure that all contractor personnel are adequately trained, possess the required credentials, and are otherwise fully qualified and skilled to perform assigned work for this SOW including staying current with developments in the field. The Contractor shall be responsible for all travel and training costs associated with maintaining required certifications and proficiencies to perform assigned duties.

B. Specific Technical requirements:

1. Bioinformatics support for Omic technologies.

NIEHS conducts gene expression, DNA sequencing as well as other genomics, proteomics, metabolomics, and epigenetics studies that require whole genome bioinformatics data analysis. Integration of different Omic data types may be an important component of bioinformatic analysis. In consultation with the COR, the contractor shall provide bioinformatics and data mining support for the analysis of gene expression, genomic sequencing, exome sequencing and other genomics data, such as proteomics, metabolomics and epigenetics data, and shall advise on the design of experiments generating these data. It is anticipated that there will be approximately 10-12 Omics-related bioinformatic studies per year.

2. Data analysis support for genomic sequencing data.

NIEHS conducts genomics studies such as ChIP-Seq, Exon-captured DNA-Seq or occasionally genomic sequencing of biological samples that require bioinformatics data analysis. These studies include next-generation sequencing of genomic samples by DNA- Seq from a variety of species. In consultation with the COR, the contractor shall provide bioinformatics and data mining support for the analysis of ChIP-Seq, or Exome-Seq data, and shall advise on the design of experiments generating these data. It is anticipated that there will be approximately 5-8 genomic sequencing bioinformatics studies per year.

3. Epigenetics support.

NIEHS conducts various epigenetics studies (e.g. studies that assess the methylation status of the DNA). These studies utilize bisulfite sequencing and/or microarray platforms. The contractor shall assist in developing and implementing strategies for identifying differentially methylation regions on DNA and histones (DMRs) within the genome. In consultation with the COR, the contractor shall provide bioinformatics and data mining support for the analysis of bisulfite DNA-Seq or other epigenetics datasets. It is anticipated that there will be approximately 2-5 bioinformatics epigenetics studies per year.

4. Toxicogenomics support.

NIEHS conducts a number of toxicogenomics studies as part of short term or long terms exposure studies followed by use of microarray (e.g., see Auerbach et al. (2010) Toxicology and Applied Pharmacology 243:300-314 or Blackshear et al. (2013) Toxicologic Pathology 42:863-876) or NextGeneration sequencing (NGS) platforms (Merrick et al., 2013 PlosOne 8:e61768). This requirement differs from requirements 1, 2 and 3 above since it focuses on transcriptomic data including mRNA transcripts, microRNA and non-coding transcript data. Toxicogenomics studies (transcriptomics applied to toxicology) generate vast amounts of gene expression data that require extensive bioinformatics data analysis such as quality control statistics, normalization, identification of differentially expressed genes and assignment of genes to pathways and networks for biological interpretation. In consultation with the COR, the contractor shall provide bioinformatics and data mining support for the analysis of RNA-Seq or microarray data. Familiarity with other toxicogenomics database resources and (e.g.

GEO, SRA) browsers (e.g. UCSC browser) will be useful. It is anticipated that there will be approximately 7-10 transcriptomics studies per year needing bioinformatics support.

5. High throughput transcriptomics (HTT).

As NIEHS embarks upon the third phase of Tox21 program, the DNTP plans to conduct transcriptomics experiments using high throughput platforms to screen large numbers of chemicals, described in the URL link.

(http://ntp.niehs.nih.gov/ntp/about_ntp/bsc/2014/june/tox21phase3_1500genes_508.pdf).

For this purpose, the contractor shall assist with selection of key genes to be included in the screening as well as selection of relevant cell lines for screening experiments. The contractor in consultation with the COR, may participate in experiment design, gene or cell line selection and bioinformatics analysis of resulting data. The data to be generated will depend upon the choice of platform used by NIEHS for HTT. The contractor shall provide bioinformatics support for a few pilot scale or large scale high throughput transcriptomics studies per year. In addition, the contractor shall provide bioinformatics support for approximately 3-5 high throughput transcriptomics studies per year needing bioinformatics support.

6. Cheminformatics support for HTS data analysis and integration.

NTP conducts high throughput screening assays on hundreds to several thousand chemicals through the Tox21 program as described in the URL links (http://ncats.nih.gov/research/reengineering/tox21/tox21.html and http://ntp.niehs.nih.gov/results/hts/index.html). The high throughput assays include more than one hundred different in vitro assays conducted on approximately 10,000 compounds (http://ntp.niehs.nih.gov/results/hts/index.html). Medium throughput screening involves in vivo dose-response assays of growth, reproduction, feeding and movement in the nematode, C. elegans and may, in the near future, include assays using zebrafish. In consultation with the COR and NTP staff, the contractor shall provide chemoinformatics support for high throughput and medium throughput screening studies.

Support includes, but is not limited to, analysis of dose-response associations, comparing responses across assays and across chemicals, use of chemical features along with other available data to make predictive models and developing approaches for combining, visualizing or comparing large volumes of data. Data integration support includes, but is not limited to, development of strategies and framework for acquiring and combining data from various sources to make it available for modeling purposes; or identifying data gaps to prioritize studies. Computational support includes, but is not limited to, development of data analysis pipeline for efficient data analysis. The contractor shall provide bioinformatics support for approximately 3-5 cheminformatic studies per year.

7. Informatics & Information mining for scientific document reviews.

Several Offices within the DNTP currently conduct evaluations of the scientific documents (Offices of Health Assessment and Translation; Report on Carcinogens;

Liaison, Policy and Review). To assist with this process, the contractor shall provide http://ntp.niehs.nih.gov/ntp/about_ntp/bsc/2014/june/tox21phase3_1500genes_508.pdf http://ncats.nih.gov/research/reengineering/tox21/tox21.html http://ntp.niehs.nih.gov/results/hts/index.html http://ntp.niehs.nih.gov/results/hts/index.html computational/informatics approaches such as text mining, and develop as well as implement methods for projects employing scientific document review approaches. The contractor shall provide bioinformatics support for approximately 7-10 text mining projects per year.

8. Support for Impact Research.

NIEHS offices (for example, the Office of Liaison, Policy and Review at the DNTP) conduct evaluations of the scientific literature to assess the impact of NTP research products. To assist with this process, the contractor shall assist in developing and implementing computational/informatics approaches including but not limited to literature mining and web-mining of the internet. The contractor shall provide bioinformatics support for approximately 5-7 text mining projects per year.

9. Informatics data extraction.

The contractor shall provide informatics support to extract data from a variety of sources including public and private databases. For example, any Tox21 chemicals or transcript expression data may be extracted from databases; data integration and mining may be requested from documents in EPA dockets. The contractor shall provide bioinformatics support for approximately 5-7 informatics data extraction projects per year.

10. Support for Study Designs.

It is anticipated that, over the course of this contract, additional study designs or experiment types may be adopted by the NIEHS, which may require bioinformatics analysis methods specific to these designs. Contribution to study design shall include, but is not limited to, types of data reduction methods employed such as clustering analysis or PCA plots, pathway analysis employed such as KEGG pathways, IPA analysis or GSEA or support vector machine analysis. The contractor shall provide bioinformatic support for approximately 5-7 study design projects per year.

11. Support for New Bioinformatics Method Development.

As directed by the COR, the contractor shall assist in the development of write GUI-based programs (Graphic User Interface) using programming languages including, but not limited to, Java, Python, or R, that incorporate new bioinformatics, text mining or informatics methods developed under the contract. The contractor shall provide bioinformatics support for 3-5 projects each year involving software development.

12. Publication and Meeting Presentation Assistance.

The contractor shall provide assistance to DNTP and DIR scientists in organizing data for publication program documents or peer-reviewed publications. The contractor shall provide assistance to NIEHS researchers in preparing for presentations at meetings. Such assistance shall include, but is not limited to, constructing graphs, tables and figures from data; providing written text to summarize methods and results for publication or presentations; providing relevant citations and references to support analytical procedures; providing power point slides that summarize data analysis approaches;

making presentations of data to study design teams in DNTP and DIR to discuss and interpret data, and providing assistance in entering data files into public databases (e.g.

GEO, SRA) as required for publication. The contractor shall provide bioinformatics support in publication assistance and meeting presentations for 8-10 publications and presentations each year.

13. Section 508 Conformance

Requirements for accessibility based on Section 508 of the Rehabilitation Act of 1973 (29 U.S.C. 794d) are determined to be relevant for the Statistical Support contract. In order to conform to the Section 508 Electronic and Information Technology Accessibility Standards, the contractor shall perform all work required under this contract in compliance with the provisions delineated in the Code of Federal Regulations (CFR) Title 36 (36 CFR Part 1194) and outlined below.

The following Section 508 accessibility technical standards apply to the tasks identified in this SOW:

• 1194.21—Software applications and operating systems

• 1194.22—Web based intranet and Internet information and applications

• 1194.31—Functional performance criteria

• 1194.41—Information, documentation and support

Final report deliverables shall meet the checklists at http://www.hhs.gov/web/section- 508/making-files-accessible/checklist/index.html according to the document type used for the report. Non web-based software developed under this contract shall meet Section 508 technical standards under: 1194.21, 1194.31, and 1194.41. Web-based software developed under this contract shall meet the Section 508 technical standards listed under:

1194.22, 1194.31, and 1194.41.

The checklists and standards are found at: http://www.section508.gov/. The Contractor shall refer to this website for further guidance.

14. Travel

a. Travel to Conferences: Upon prior approval by the COR and in accordance with NIH Efficient Spending policies, funds shall be provided in the contract for a limited number of trips to national conferences (e.g. two conferences such as annual meetings for the Society of Toxicology and International Society for Computational Biology) and workshops (e.g. four workshops such as Tox21 meetings, SOT’s ‘FutureTox’, NIH’s NCATS-sponsored meetings) by the contractor to be taken in support of NIEHS program. The purposes of such programmatic travel are to support DNTP programs and shall include but are not limited to: Tox21 meetings or sponsored events; discussions with academic or government collaborators involving DNTP or DIR researchers; workshops involving new methods of bioinformatics analysis; and http://www.hhs.gov/web/section-508/making-files-accessible/checklist/index.html http://www.hhs.gov/web/section-508/making-files-accessible/checklist/index.html http://www.section508.gov/ local or national meetings such as the Society of Toxicology for the contractor to make oral or poster presentations that will further the interests of DNTP or DIR programs.

b. Local Travel: The Contractor shall be required to travel daily to the NIEHS main campus and Keystone campus, and between the two facilities. The government will not reimburse for travel for the Contractor’s convenience or local travel within 1 hr of drive time of the NIEHS – Keystone Building at 530 Davis Drive, Morrisville, NC 27560. All other travel requires preapproval prior to reimbursement. The main campus is located nearby Keystone at:

NIEHS Main Campus National Institute of Environmental Health Sciences 111 T.W. Alexander Drive Research Triangle Park, NC 27709

Keystone Campus NIEHS, National Toxicology Program 530 Davis Drive Morrisville, NC 27560