Attach5DNApoolSOW.pdf

Genome Characterization Center for DNA Samples

Task Order Statement of Work for CCG projects

A. Background

Cancer is a complex and heterogeneous disease in which mutations and other genomic and epigenomic abnormalities play a role in both its initiation and progression. Accumulated research data implicate numerous somatic mutations and a more limited number of inherited mutations in carcinogenesis. Understanding cancer-specific somatic mutations can provide important clues regarding the molecular processes underlying the development and progression of certain tumors.

The objective of this Statement of Work (SOW) is to acquire Genome Characterization Center

(GCC) services for genomics studies supported by Center for Cancer Genomics (CCG) at the

NCI. CCG was established in 2011 with a mission to lead the NCI efforts in generating critical datasets required to catalog the genomic alterations seen in human tumors. CCG promotes genomic data sharing and development of analytical tools and computational approaches to improve understanding of the large-scale, multidimensional genomic data. The Genome

Characterization Centers contracts solicited here are key components of CCG’s centralized approach to have all the characterizations conducted on biomolecules from the same biospecimens for optimal analytical integration for data comparability.

B. Scope

The Genome Characterization Centers provide comprehensive genomic characterization of tumor and normal samples. These types of characterizations should be conducted using validated methods in a high-throughput fashion at the start of the project. The contractor shall demonstrate large scale operation capability to support an expanding list of CCG supported genomic projects.

The sample material such as molecular analytes to be characterized will be provided by the

Biospecimen Processing Center (BPC) funded as a separate NCI contract. The quantity and quality requirements of analytes for each project are centrally verified by the BPC.

The objective of this SOW is to acquire high-resolution, systematic, comprehensive (genome-wide) characterization services of cancer-related genomic alterations.

The contractor shall function as a fundamental resource and play a key role in the CCG research programs. Key goals shall include ensuring that standards are developed, implemented, continually improved, and maintained to support the entire genomic characterization pipeline.

Study variables shall be minimized with rigorous Quality Assurance/Quality Control (QA/QC) of all parts of the operation.

The contractor shall offer the types of characterizations using validated methods in a high-throughput fashion at the start of the project. The biomaterial for these studies (DNA, RNA, or other types of samples required by a platform) will be provided by the BPC of CCG. The aim is to have all molecular characterizations conducted on biomolecules from the same biospecimens for optimal analytical integration for data comparability.

The contractor shall support all genomics projects with following services in scope:

1. Receive biomaterial from BPC

2. Operate molecular characterization pipelines

3. Improve and optimize performance of characterization pipelines

4. Implement quality control procedures

5. Support informatics and data delivery

6. Perform transition activities

C. Objectives and Requirements

Objective 1. Receive biomaterial from BPC

1. The contractor shall describe plans to execute Material Transfer Agreements (MTAs) and

Data Usage Agreements (DUAs). The contractor shall describe plans to implement protocols for receiving and handling biomaterial samples. The contractor shall develop a

Standard Operating Procedure (SOP) to receive and manage the types of sample aliquot provided for characterization by BPC. These samples shall be accompanied by a manifest file including de-identified information regarding the samples from BPC.

2. The contractor shall abide by NIH patient and data protection policies for all participating

CCG genomics study.

(https://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm)

3. The contractor shall have a Standard Operating Procedure (SOP) governing the withdrawal of a participant from a CCG genomics study. Notification of such withdrawal will come from BPC. The SOP shall include documentation of confirmation and actions following such notification.

Objective 2. Operate molecular characterization pipelines

The contractor shall describe high-throughput, cost-effective technology platforms to characterize comprehensively genomic, epigenomic or transcriptome alterations in one or more molecular characterization platforms described below.

An appropriate platform may be a current version technology evaluated in large scale genomic research programs funded by NCI, such as The Cancer Genome Atlas (TCGA). Other platforms can be considered if they can produce high quality data when used in a high-throughput setting and there have been sufficient data to statistically validate the capabilities of the proposed platform. The results of genomic feature detection using the chosen platform should have been corroborated statistically by other validated technologies in published comparative analyses.

• The contractor shall be able to conduct technologically state of the art, comprehensive, reproducible and quality controlled characterization of the biomolecules from cancer samples and appropriate matched controls provided by a BPC.

• The contractor shall build up characterization pipelines to specified minimum operational capacity within the first three months of contract award. The minimum operational capacity is described for each platform under “Characterization Platforms”.

• The contractor shall operate characterization pipelines with the minimum capacity for each protocol. The volume of cases requested may vary up or down from the minimum operational capacity over the course of task order performance period. In general, the contractor shall plan to increase their operational capacity above the minimum after the first year to accommodate potentially higher work volumes from task orders. The contractor shall provide pricing for the case volume specified in the Additional Business

Proposal Instructions.

• All GCC genome characterization platforms shall utilize appropriate SOPs, developed and validated by the contractor to minimize variability in laboratory processes. The SOPs shall be maintained and made public with approval from the Contracting Officer’s

Representative (COR).

• The contractor shall develop and maintain a quality control process for production pipelines at the start of the contract. This process shall include evaluating quality metrics for data generated (e.g. sufficient coverage and depth) as well as capturing platform-specific metadata generated in production. The contractor shall continuous monitor systemic performance such as batch effects in the production pipeline.

• The contractor shall develop automated process to deposit characterization data and metadata to a NCI repository, such as the NCI's Genomic Data Commons (GDC) within four weeks after data are generated and passed quality control.

Characterization Platforms

Characterization platforms include:

1) Whole Genome Sequencing (WGS), low coverage depth:

a. Perform WGS in DNA extracted from FFPE samples with a validated, documented SOP methodology.

b. Perform WGS in DNA extracted from fresh frozen samples with a validated, documented SOP methodology.

c. Perform WGS with minimal DNA quantities from samples of limiting size, such as core needle biopsies with a validated, documented SOP methodology.

d. Produce WGS for both frozen and FFPE cases with the following requirements:

i. Quality control metrics:

1. Average coverage of bases will be 15X or greater.

2. >85% of bases in genome will have >5X coverage

3. At least 30 Gb sequence per sample

ii. Turnaround time: within 4 months

iii. Minimum operational capacity: 100 cases/month; 1200 cases/year

2) Whole Genome Sequencing (WGS), high coverage depth:

a. Perform WGS in DNA extracted from FFPE samples with a validated, documented SOP methodology.

b. Perform WGS in DNA extracted from fresh Frozen samples with a validated, documented SOP methodology.

c. Perform WGS with minimal DNA quantities from samples of limiting size, such as core needle biopsies with a validated, documented SOP methodology.

d. Produce WGS for both frozen and FFPE cases with the following requirements:

i. Quality control metrics:

1. Average coverage of bases will be 30X or greater for non-tumor and 80X or greater for tumor.

2. >85% of bases in genome will have >15X coverage for non-tumor and >40x for tumor.

3. At least 220 Gb sequence per sample

ii. Turnaround time: within 4 months

iii. Minimum operational capacity: 100 cases/month; 1200 cases/year

3) Whole Exome Sequencing (WES):

a. Perform WES in DNA extracted from FFPE samples with a validated, documented SOP methodology.

b. Perform WES in DNA extracted from fresh frozen samples with a validated, documented SOP methodology.

c. Perform WES with minimal DNA quantities from samples of limiting size, such as core needle biopsies with a validated, documented SOP methodology.

d. Develop methods and SOP for WES using different capture methods as required by the Program Office

e. Produce WES for both frozen and FFPE cases with the following requirements:

i. Quality control metrics:

1. Average coverage of bases within the targeted exome will be 150X or greater.

2. >75% of reads will be on-target

3. >85% of reads will be on-target +/- 100 bp

4. >85% of bases in target exome will have >40X coverage

5. >75% of bases in target exome will have >80X coverage

6. At least 8 Gb sequence per sample

ii. Turnaround time: within 3 months

iii. Minimum operational capacity: 100 cases/month; 1200 cases/year

4) Deep Sequence Targeted Validation:

a. Perform Validation in DNA extracted from FFPE samples with a validated, documented SOP methodology.

b. Perform Validation in DNA extracted from fresh Frozen samples with a validated, documented SOP methodology.

c. Perform Validation with minimal DNA quantities from samples of limiting size, such as core needle biopsies with a validated, documented SOP methodology.

d. Produce Validation for both frozen and FFPE cases with the following requirements:

i. Quality Control Metrics:

1. Average Depth of Coverage for targets >400x

2. Minimal coverage per target: 100x

3. Minimal number of targets assayed: 100

ii. Turnaround time: within 1 month

iii. Minimum operational capacity: 100 cases/month; 1200 cases/year

5) Whole Genome Methylation Sequencing (WGMetSeq):

a. Perform WGMetSeq in DNA extracted from FFPE samples with a validated, documented SOP methodology.

b. Perform WGMetSeq in DNA extracted from fresh frozen samples with a validated, documented SOP methodology.

c. Perform WGMetSeq with minimal DNA quantities from samples of limiting size, such as core needle biopsies with a validated, documented SOP methodology.

d. Develop methods and SOP for WGMetSeq using different capture methods as required by the Program Office

e. Produce WGMetSeq for both frozen and FFPE cases with the following requirements:

i. Quality Control Metrics:

1. Average Depth of Coverage >15x

2. >75% of reads will be on-target

3. At least 20 Gb sequence per sample

ii. Turnaround time: within 3 months

iii. Minimum operational capacity: 100 cases/month; 1200 cases/year

6) Methylation Array (MetArray):

a. Perform MetArray in DNA extracted from FFPE samples with a validated, documented SOP methodology.

b. Perform MetArray in DNA extracted from fresh frozen samples with a validated, documented SOP methodology.

c. Perform MetArray with minimal DNA quantities from samples of limiting size, such as core needle biopsies with a validated, documented SOP methodology.

d. Produce MetArray for both frozen and FFPE cases with the following requirements:

i. Number of CpG sites interrogated >400K

ii. Turnaround time: within 1 month

iii. Minimum operational capacity: 100 cases/month; 1200 cases/year

Objective 3. Improve and optimize performance of characterization pipelines

Because technologies have been evolving rapidly, the contractor shall continue to plan for technology improvements during the execution of the project. The contractor shall propose specific efforts to improve and optimize the prescribed technology platforms or switch to more advanced platforms when properly validated. In general, improvements/optimization efforts sought include, but are not limited to:

1. Increasing characterization pipeline throughput

2. Enhancing detection sensitivity and/or resolution

3. Optimizing genome characterization coverage

4. Obtaining high quality data sets from small tumor samples

5. Reducing unit costs per platform

• The contractor shall be able to increase operational capabilities beyond the initial minimum capacity requirement after first year as CCG projects progress. CCG will provide the contractor advanced estimates of needed capacity throughout the project.

• The contractor shall develop plans to implement and validate new improvements of the characterization platforms when such advances become available. For example, these improvements could be enhanced sensitivity and resolution in the detection of cancer-associated genomic, epigenomic or transcriptome alterations.

• Throughout the project, the GCC shall implement SOPs to minimize variability and to improve detection sensitivity and resolution in laboratory processes. The contractor shall make changes with consultation and approval from the CCG program officials.

• The contractor shall plan to take advantage of technology development in selected characterization pipelines. The contractor shall evaluate relevant emerging technologies including complete change in platform utilized, should it benefit the project (e.g., switching from array-based characterization methods to sequencing-based methods). Technology platform changes must be validated for high throughput production and implemented with approval from CCG program officials.

Objective 4. Implement quality control procedures

• The contractor shall provide specific quality assurance and quality control procedures to monitor the performance of characterization pipelines.

• Quality checking shall be performed on characterization data before submission to the

CCG data repositories. The contractor shall work with the CCG COR to define specific quality criteria for each project. These specific criteria shall be established at the start of each project and monitored throughout the project.

• The contractor shall continuously monitor and identify sources of systematic error and bias. The contractor shall implement necessary procedures to make corrections to achieve experimental reproducibility.

• The contractor shall implement necessary system to provide reporting on the performance of characterization pipelines.

Objective 5. Support informatics and data delivery

Public availability of data/information generated by NCI projects will be critical to facilitate disease-relevant discoveries. Therefore, sharing all rigorously verified data in a timely manner is essential for this contract. All data acquired by the contractor must be made available through the

GDC in timely manner. The contractor is required to submit a Data Sharing Plan documenting how and when data will be released and shared. The Data Sharing Plan must be consistent with the goals of CCG and NCI genomic programs, with adherence to NIH data sharing policies for the protection of human subjects (https://www.cancer.gov/grants-training/policies-process/nci-policies/genomic-data/about-policy).

• The contractor shall develop informatics system to support sample receiving, sample tracking in pipelines and data submission to designated NCI data repository such as GDC. The contractor shall develop informatics support to meet the data submission requirements by the designated NCI data repository.

• The informatics support shall interact with the CCG COR and GDC to ensure that data release is conformant to CCG project requirements.

• The contractor shall ensure that data submitted to the NCI GDC are compliant with GDC data submission requirements. The precise content of the data to be shared may vary on the data collected for the research projects. Nevertheless, the contractor will be expected to adhere to the general data sharing principles established by the CCG.

• The contractor must acknowledge and agree that all data, datasets, algorithms, models, and protocols generated through this contract will rapidly become available through the GDC for public use in accordance with the data release requirements. Sharing/dissemination of intellectual property should also be described in the Data Sharing Plan.

• The contractor should develop plans for data evaluation and data submission process. The contractor should describe the expected schedule for data sharing, the format of the datasets, any documentation and analytic tools, and data storage capabilities needed. NCI requires that all data, datasets, and algorithms be released within 30 days to designated databases as they are generated and verified. Algorithms and software tools must be released as an open source. A plan to release the data upon completion of the funding period is not acceptable. Data release plans should aim for immediate and automatic submissions once the data are verified. In addition, the contractor shall demonstrate capability to store and maintain the anticipated large amounts of genomic data in-house on a temporary basis and propose appropriate arrangements with the CCG data repositories for permanent storage and maintenance.

https://www.cancer.gov/grants-training/policies-process/nci-policies/genomic-data/about-policy https://www.cancer.gov/grants-training/policies-process/nci-policies/genomic-data/about-policy

Objective 6. Perform transition activities

• First 3-month Transition-In Plan:

The contractor shall provide a transition in plan for the first three months of the contract. The plan shall describe major steps to ramp up the production capability to meet at least the minimum case requirements within three months of contract award. The contractor shall prepare necessary documentations such as Material Transfer Agreements (MTAs), Data

Usage Agreements (DUAs) and Standard Operating Procedures (SOPs) required to perform the contract.

• Last 6-month Transition-Out Plan:

The contractor shall provide a closeout transition plan for the last six months of the contract.

The plan shall include schedules and mechanisms for transmission all data and materials to parties designated by the NCI contracting officer or as contractually obligated. The contractor shall be prepared to execute the transition and closeout plans prior to expiration of the contract.

D. Section 508

The following Section 508 Standards are applicable to this procurement and will be included in the resulting solicitation.

o 602 Support Documentation o 603 Support Services o All WCAG A & AA Success Criteria apply except:

2.4.1 Bypass Blocks

2.4.5 Multiple Ways

3.2.3 Consistent Navigation

3.2.4 Consistent Identification