SOURCES SOUGHT
R -- NIEHS Mouse Methylome Project
- Notice Date
- 2/28/2011
- Notice Type
- Sources Sought
- NAICS
- 541690
— Other Scientific and Technical Consulting Services
- Contracting Office
- Department of Health and Human Services, National Institutes of Health, National Institute of Environmental Health Sciences, Office of Acquisitions, Office of Management, 530 Davis Drive, Durham, North Carolina, 27713, United States
- ZIP Code
- 27713
- Solicitation Number
- HHS-NIH-NIEHS-OA-SS-11-128
- Archive Date
- 3/30/2012
- Point of Contact
- Deitra Lunney, Phone: 919-541-0387
- E-Mail Address
-
lunney@niehs.nih.gov
(lunney@niehs.nih.gov)
- Small Business Set-Aside
- N/A
- Description
- This is a Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding the availability and capability of all qualified sources to perform a potential requirement."The primary goal of this NIEHS project will be use of NextGen sequencing technologies to create a high resolution map of the mouse liver methylome from three different mouse stains. These strains show dramatically different incidences of spontaneous liver tumors. A major premise of this project is that the variable cancer incidence among these mouse strains may be due in part to cytosine methylation in critical tumor suppressor genes and other regulatory regions of the genome that affect associated pathways for liver cancer susceptibility and its heritability across generations. A NextGen Sequencing Support Contract will provide for the following: 1) NextGen DNA sequencing services, and 2) supplementary targeted studies for follow up on generated genomic data. Subsequent studies may examine chemical-induced changes in DNA methylation at target genomic sites that could include complementary studies in global protein and metabolite expression. all qualified sources to perform a potential requirement. Background. The methylome is an individual's genome wide pattern of cytosine methylation. DNA methylation is an important epigenetic modification of the genome that plays a major role in development, toxicity and disease. Methylation occurs on cytosines of CpG dinucleotides, a large proportion of which are methylated in mammals. Clusters of unmethylated CpGs or ‘CpG islands' are often found at the 5'-regulatory regions of many genes. These CpGs may become hypermethylated to mediate transcriptional silencing which often occurs in many cancers to downregulate tumor suppressor gene expression or promote pathways in tumor development. Many synthetic and natural chemical undergo 2 year exposure studies in rodents for carcinogenic activity for which a series of genetic and possible epigenetic alterations likely contribute to malignant transformation. However, many basic questions remain about epigenetic variation in contributing to disease relative to environmental chemical exposure. Recent developments in high throughput or ‘NextGen' DNA sequencing technologies now enable sufficiently rapid genome-wide determination of cytosine methylation, DNA sequence variation, and RNA sequence at base pair resolution. Accumulation of sequence reads in each sample permits sufficient redundancy for accurate base pair assignment to a genome (DNA-Seq) or transcriptome (DNA-Seq). Determination of methylated DNA sites can be accomplished by chemical conversion of unmodified cytosines to thymidine with bisulfite, followed by genomic DNA sequencing. Two parental strains C57BL/6N and C3H/HeN and their F1 hybrid offspring (B6C3F1/N) show very different incidences in spontaneous liver tumors in long term bioassay tests. Determination of the methylome assisted by sequencing of their respective genomes and transcriptomes would provide great insight into the underlying process of tumorigenesis. Confirmation of observed methylated sites can be performed by differential methylation restriction digest or affinity capture to enrich methylated DNA sequences followed by high throughput sequencing and bioinformatic data mining for a targeted interrogation of genomic regions of interest. A provision for metabolomics or proteomic analytical capabilities are intended to provide a targeted level of resources to complement NextGen sequencing data. Purpose and Objectives. The major objectives of this contract are to use NextGen Sequencing technologies to perform the following: 1) define the mouse methylome linked to the genomic sequence and gene expression data of three mouse strains, and 2) perform supplementary studies for a limited follow up validation on genomic methylation and expression data in these mouse strains. Such subsequent studies may examine chemical-induced changes in DNA methylation at target genomic sites that could include complementary studies in global protein and metabolite expression. Project requirements. Samples for NextGen sequencing and other studies will be on three strains of mouse liver. Liver samples from all mice in this project will be collected and flash frozen by NIEHS. All sequencing libraries will be prepared by NIEHS with appropriate quality metrics. The offeror will provide NextGen sequencing capabilities of paired end reads that will be primarily performed on an Illumina HiSeq2000 instrument. Additional proteomic and metabolomic technology platforms proposed by the offeror are intended to complement and extend results from the primary DNA sequencing efforts. DNA sequencing data generated by the contractor shall be regularly sent electronically to NIEHS for permanent storage and analysis. The project will proceed in three phases. The first and second phases will involve NextGen DNA sequencing of each strain to define the genome by DNA-Seq technologies. RNA-Seq analysis for gene expression will be performed upon liver RNA to determine the liver transcriptome. BIS-DNA-Seq will be performed upon libraries constructed from bisulfite reduced DNA isolated from each liver for measurement of site-specific methylation of DNA,. These two phases will consist of 15-20 liver samples over a period of two years. In third phase of study, any additional replicates or targeted re-sequencing to validate specific methylation sites will be performed. Validation of specific methylated CpG sites would be performed sequencing libraries formed after methylation specific restriction enzyme digestions. Furthermore, there may be the need for longer read DNA-Seq using Roche 454 sequence instruments to ensure contiguous sequence data over highly repetitive genomic regions. The degree of required sequence coverage for each of the three sequencing strategies will be guided by results and bioformatic analysis. It isanticipated that 15-20 fold coverage will be needed for DNA-Seq, DNA-Seq and BisDNA-Seq. The provision of metabolomics or proteomic analytical capabilities are intended to provide a targeted level of resources to complement NextGen sequencing data. Metabolomics will primarily be an NMR based platform but may include liquid chromatography-mass spectrometry (LC-MS). Proteomics will be mass spectrometry-based platforms for protein quantitation and identification. It is anticipated that NextGen Sequencing and supportive analysis by metabolomics/proteomics would be provided by using instruments and resources of one facility or research institution under one contract. NIEHS will furnish the biological samples for analysis. No equipment or supplies will be furnished by NIEHS under this contract. Anticipated period of performance. It is anticipated the contract will have a base year and two one-year option periods. The contract type is expected to be firm fixed price. Other important considerations. The offeror will frequently update the chemistry and software of the Illumina HiSeq2000 sequencing instrument to maximize number of paired-end sequence reads per lane. Current versions of Illumina chemistries and imaging software as of January 2011 yield about 60 million reads per lane. It is anticipated that this number will increase substantially in 2011. Capability statement /information sought. Respondents are requested to provide a Capability Statement of no more than five to eight (5-8) pages at 8.5 x 11 size which can be delivered electronically or by email to the Contracting Officer at email address of lunney@niehs.nih.gov or postal address to, Deitra Lunney, Office of Acquisitions, NIEHS, PO Box 12233, Mail Drop: K1-04, Research Triangle Park, NC 27709. March 28, 2011 is the post-marked due date for delivery of Capability Statement by interested respondents. The Capability Statement should include the following: (a) The respondent's interest and ability to perform contract objectives. Respondent should provide information to briefly address the following areas. (b) Description of the facilities that will perform the subject services, (c) Description of staff and staff expertise, (d) Description of relevant instrumentation, (e) Description of current in-house capability and capacity to perform the work; (f) Description of respondent experience that includes prior completed projects of related nature; (g) Respondents' opinions about the feasibility of the potential requirements for the acquisition proposal, possible solutions and approaches for innovative ideas or concepts relating to goals of the proposal. Additionally, the Capability Statement should also address the following administrative items: (a) the respondents' DUNS number, organization name, address, person as point of contact, and size and type of business (e.g., 8(a), HUBZone, etc) pursuant to the applicable NAICS code number 541690/$7 mil; (b) respondents' technical and administrative points of contact, including names, titles, addresses, telephone and fax numbers, and e-mail addresses. Disclaimer and Important Notes. This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed. Information provided will be used to assess tradeoffs and alternatives available for the potential requirement and may lead to the development of a solicitation. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. Any solicitation resulting from the analysis of information obtained will be announced to the public in Federal Business Opportunities in accordance with the FAR Part 5. However, responses to this notice will not be considered adequate responses to a solicitation. Confidentiality. No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s).
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