RNA_Seq SOW_2018_06_1.docx

RNA Sequencing

FEDERAL AVIATION ADMINISTRATION

CIVIL AEROSPACE MEDICAL INSTITUTE

FUNCTIONAL GENOMICS LABORATORY

STATEMENT OF WORK

1.0 Introduction and Overview

The Civil Aerospace Medical Institute (CAMI) is the medical certification, education, research, and occupational medicine wing of the Office of Aerospace Medicine (AAM) under the auspices of the Federal Aviation Administration (FAA’s) Office of Aviation Safety (AVS). The mission of the Aerospace Medical Research Division of CAMI (AAM-600), located at the Mike Monroney Aeronautical Center (MMAC), in Oklahoma City, OK, is “to develop new and innovative ways to support FAA regulatory and advisory missions to improve the safety of humans in civilian aerospace operations.” As such, its goal is to “Continuously maintain the Absorptive Capacity for applying Science, Medicine, Bioengineering, and Technology to unrelentingly enhance human safety.”

The aerospace medical research program has been formulated to keep abreast of emerging human safety risk issues such as those brought by (1) the aging pilot population and changes in their health condition; (2) advances in pharmacology, therapeutic tools, and surgical procedures, and (3) improved aircraft materials, equipment, cabin configurations, life support systems, and evacuation assistive devices – all of which may affect survival from an aircraft accident. The program has also been designed to address the complexity of software, technology, and systems integration practices as these continue to evolve. For example, advances in computational biology, modeling & simulation, and tools to facilitate the integration of very large data sets containing disparate information will lead to improved knowledge management and decision-making in aerospace medicine.

The Functional Genomics Research Team of the Aerospace Medical Research Division at CAMI is a pioneer in biomarker research pertinent to aviation safety and is the requiring organization.

1.1 Requirement

The Federal Aviation Administration (FAA) Civil Aerospace Medical Institute (CAMI), Functional Genomics team (AAM-612) has a requirement for ribonucleic acid sequencing services and library preparation preliminary to gathering sequence data. The team needs to collect sequence data from total RNA samples, as the second phase of a larger study aimed to assess aerospace-relevant stressors in human subjects. The Contractor will receive total RNA samples from the Functional Genomics team; perform globin- and ribosomal-reduced stranded total RNA library preparation, sequencing, and quality assessment as appropriate on these samples; and provide the resulting sequence data to the Functional Genomics team as specified in this Contract. The Functional Genomics team will use the sequence data (FASTQ files) as the basis for a study of gene expression differences to be conducted by the Functional Genomics team.

1.2.1 Scope of Work

The intent of this acquisition is to obtain a Three (3) (Base with two (2) one-year renewable options) “D” type contract in accordance with this Statement of Work to provide total RNA library preparation and sequencing services from an estimate of roughly 270-480 samples provided by the Government. The Contractor must provide to the Functional Genomics team the following:

· Sequence data in the form of FASTQ files. This must consist of a minimum of 50 million read pairs (i.e., 50 million 2x150 bp paired-end reads) per sample of human nucleic acid sequence, that pass initial quality assessment in the Illumina instrument quality assessment pipeline from stranded total RNA RNA-Seq performed as specified in this contract, and is of acceptable quality level.

· Clear association of reads with a sample ID provided by the Functional Genomics team.

· Clear descriptions of all methods used must be disclosed to the Functional Genomics team, as would be expected for inclusion of sequencing data in the peer-reviewed literature (e.g., instrument/kit used).

The Contractor must generate this sequence read data with the following performance requirements:

· Stranded RNA-Seq sequencing must generate paired end reads of at least 150 bp (2 x 150 bp).

· All libraries must be constructed using the same techniques/kits, and all libraries must be sequenced on the same platform, unless negotiated with and approved by the Functional Genomics team.

· Prior to or as part of library preparation, total RNA samples must be globin and ribosomal RNA depleted.

· Libraries must NOT be polyA selected. That is, the Contractor must perform total RNA (not mRNA) RNA-Seq.

· Library preparation should follow standard industry-accepted practices; any custom approaches of the Contractor that could impact sequence quantity or quality, or that could result in sequencing bias, must be discussed with and agreed to by the Functional Genomics team.

· Standard techniques should be used to assess library quality, and shall be provided to the Functional Genomics team if requested (e.g., bioanalyzer traces).

· Standard quality assessment/control approaches associated with library construction and sequencing must be performed by the Contractor.

· Sequence data must be collected on Illumina HiSeq, NovaSeq, or NextSeq instruments.

· Multiplexing is allowed within the parameters of the individual instrument being used to yield the minimum number of acceptable quality reads per sample. If multiplexing is performed, the Contractor must demultiplex clean reads, and ensure clear association of reads with the sample ID provided by the Functional Genomics team.

· Sequencing data must be returned to the team in FastQ format in clean (i.e., passing Illumina’s instrument quality assessment pipeline) de-multiplexed form. The above requirement for no less than 50 million paired-end (2x150 bp) reads applies to the clean data.

· Appropriate levels of randomization to mitigate potential batch effects and use of spike-in controls, are to be negotiated between the Contractor and Functional Genomics team.

1.2 Period of Performance

Base Year: September 1, 2018 - August 31, 2019 Option Year 1: September 1, 2019 - August 31, 2020 Option Year 2: September 1, 2020 - August 31, 2021

2.0 Place of Performance:

The Contractor must perform library preparation suitable for samples to be sequenced on an Illumina HiSeq, NovaSeq, or NextSeq sequencing instrument, sequence data generation on an Illumina sequencing instrument, and initial quality assessment at the Contractor’s location.

3.0 Government Provided Samples/Services

3.1 Government Supplied Samples

The Functional Genomics team will provide human RNA samples at a mutually agreed upon concentration and amount to the Contractor with sample-specific quantity data as assessed by spectrophotometry using instrumentation of the Functional Genomics team’s choice. If requested by the Contractor, the Functional Genomics team will provide an appropriate computer storage media for transfer of the data from the Contractor to the Functional Genomics team at the appropriate time. Otherwise the Contractor will be responsible for data transfer (e.g., ensuring data remains available for online download in a manner accessible to the Functional Genomics team for at least 30 days).

4.0 Contractor(s) Responsibility

4.1 Contractor(s) Services

The Contractor(s) must provide all personnel, facilities, equipment, supplies, and reagents for library preparation appropriate for the sample type, to gather the sequence data on an instrument from the Illumina family of sequencing instruments (such as the HiSeq, NextSeq, or NovaSeq), and perform initial data quality assessment for the nucleic acid sequence data. Contractor will provide personnel experienced in the performance of the globin and ribosomal RNA depletion steps for RNA samples, stranded library preparation from RNA samples, Illumina sequencer operation, and Illumina data quality software. Further, the Contractor will provide sequence data of the quantity per sample and quality delineated in the Scope of Work Requirements above, i.e., no less than 50 million read pairs (50 million paired-end 2x150 bp reads), per sample of acceptable quality from stranded total RNA sequencing.

The Contractor will be responsible for all aspects of sample security from receipt of the samples until the associated RNA samples and final libraries are consumed or returned to the Functional Genomics team, AND all intermediate samples/byproducts are destroyed. Unused RNA sample and excess final library material not consumed in generation of sequence data must be returned to the Functional Genomics team via overnight shipment on dry ice within 12 months of completion of sequencing of the sample or by the termination of the Contract (whichever comes first). All items required for shipment of the unused RNA and excess final library will be the Contractor’s responsibility. Intermediate materials/sample generated by the Contractor from the samples provided by the Functional Genomics team, if any, must be destroyed by the Contractor within 12 months of completion of sequencing or by the termination of the Contract (whichever comes first). The Contractor will be responsible for data and sample security, and ensuring all data generated by the Contractor in support of this Contract is not published or disseminated by the Contractor or its affiliates.

5.0 Qualifications:

5.1 Facilities and Capabilities

The Contractor must provide a description of laboratory facilities and key equipment that will be used to complete the work. The Contractor must possess Illumina sequencing equipment (HiSeq, NovaSeq, and/or NextSeq and any necessary supporting equipment – i.e., the platform the Contractor will use for sequencing), equipment for quality and quantity assessment as appropriate for library preparation from total RNA and sequencing, and equipment for library construction.

The Contractor must provide evidence that it has performed research similar or greater in scope to that described in this Statement of Work, including preparation of total RNA-Seq paired end read libraries and Illumina sequencing of total RNA samples, with globin and ribosomal depletion.

The Contractor must be able to process samples (including all steps for conversion of total RNA sample into sequence data) at an average rate of 100 samples/month or faster.

The Contractor must provide evidence that they have been performing RNA-Seq on Illumina instrumentation since at least Jan. 2015.

5.2 Personnel

The Contractor must provide a description of expertise for key personnel who will be involved in processing RNA samples, constructing libraries, performing quality assessment, and sequencing. The Contractor must provide qualified trained individuals experienced in the work they perform. The Contractor must provide evidence that the Contractor and its personnel have performed similar work.

6.0 Deliverables:

The Contractor(s) must provide the following:

1. Within 15 business days of Contract award, the Contractor must provide the name and contact information for the primary Point of Contact, and a Backup. This Point of Contact or Backup must respond to questions or inquiries posed by the FAA within 10 business days. If both Point of Contact and Backup are to be unavailable for more than 10 business days, prior to their becoming unavailable alternate contact information must be provided for a source that will respond.

2. Sequence data from each provided sample according to the sequencing quantity and quality metrics laid out above on samples provided to the contractor by the Functional Genomics team. Sequence data must be in FastQ format as specified above (Scope of Work). Sequence data should be returned on average within 90 days of receipt of samples or faster, and in no case more than 180 calendar days of sample receipt.

3. The Contractor must not retain any sequence data for more than 12 months following provision of said data to the Functional Genomics team; at this time or by termination of the Contract (whichever comes first, but not until verifying successful data transfer to the Functional Genomics team) the Contractor must permanently delete any FastQ files and sequence data that it or its affiliates have retained and provide a statement to the Functional Genomics team attesting to its destruction.

4. Unused RNA samples and excess final libraries not consumed/destroyed in production and sequencing of libraries or quality assessment, must be provided by the Contractor to the Functional Genomics team within 12 months of sequencing or by the termination of this Contract (whichever comes first). These specimens must be clearly identifiable (associated with the original sample ID provided by the Functional Genomics team, and described as initial .

5. All intermediate samples/byproducts not consumed/destroyed in production and sequencing of libraries or quality assessment, will be destroyed by the Contractor and a statement or evidence in Contractor format provided to the Functional Genomics team ensuring their destruction within 12 months of completion of sequencing or by the termination of this Contract (whichever comes first).

6. Description of methods used in library preparation, sequencing, and quality assessment adequate for inclusion of library preparation and sequencing methods in the peer-reviewed literature for publications presenting the sequencing results. This includes names of the sequencing instrument and main kits used for library construction, cleaning/demultiplexing protocol, and statement of the number of samples sequenced per lane.

7.0 Invoicing

Batch payments will be provided within 3 months following provision of sequencing data from the Contractor to the Functional Genomics team, in accordance with the number of samples for which sequencing data is provided.

8.0 Definitions/Acronyms

As used throughout this contract, the following terms shall have the meaning set forth below and specified as applicable:

8.1 General Definitions

· Aircraft Certification - The prescribed safety standards outlined under specific Federal Aviation Regulations, which must be met before the FAA issues a type certificate for new aircraft, engines or propeller models.

· Acceptable Quality Level (AQL) - The standard at which service is considered satisfactory as agreed upon by the Contractor and the Government.

· Alternative Dispute Resolution (ADR) - Process for the resolution of disputes regarding work determined to be unsatisfactory.

· Aviation Safety (AVS) Quality Management System (QMS) (https://employees.faa.gov/org/linebusiness/avs/programs/qms/) AVS- is committed to continuously improving the world's safest aerospace system. AVS fulfills this commitment by responding to our stakeholders, supporting the interests of the flying public, valuing the contributions of each employee, and meeting the requirements of the AVS quality management system.

· Compatible - The quality of handling data and programs devised from one type of computer system to another

· Computer Security -The Safeguarding of computing resources against unauthorized use, especially the protection of data from deliberate or accidental damage, unauthorized change, or disclosure of controlled or Privacy Act material.

· Contractor - The term Contractor as used herein refers to both the prime Contractor and any subcontractor. The prime Contractor shall provide a single point of contact (an employee of the prime) to coordinate all tasking’s, schedules and requirements. The contractor shall ensure that his subcontracts (if any) comply with the provisions of this contract. The onsite supervisor must be an employee of the Prime contractor.

· Contracting Officer (CO) - One with authority to enter into, administer, and/or terminate contracts and make related determinations.

· Contracting Officer’s Representative (COR) - One who is designated and authorized in writing by the CO to be responsible for surveillance/monitoring of the Contractor's performance.

· Contractor Owned Property- All property used on this contract that is owned or furnished by the Contractor.

· Government Owned Property- All property owned by or leased to the Government or acquired by the Government under the terms of the contract. Government property included both Government-furnished property and Contract acquired property as defined in AMS Guidance T3.10.3.

· Quality Assurance (QA) - Those actions taken by the Government to assure services meet the acceptable quality level established by the contract between the Contractor and Government.

· Quality Control (QC) - Those actions taken by the Contractor to ensure Contractor performance meets the requirements of the contract.

8.2 Acronyms

· (AAM) Office of Aviation Medicine

· (AMRD) Aerospace Medical Research Division

· (AQL) Acceptable Quality Level

· (AVS) Office of Aviation Safety

· (CAMI) Civil Aerospace Medical Institute

· (CDRL) Contract Deliverable Requirement List

· (CO) Contracting Officer

· (COR) Contracting Officer’s Representative

· (FAA) Federal Aviation Administration

· (FAR) Federal Aviation Regulation

· (FOIA) Freedom of Information Act

· (ICD) International Classification of Disease

· (IRB) Institutional Review Board

· (ISO) International Organization for Standardization

· (MMAC) Mike Monroney Aeronautical Center

· (NTSB) National Transportation Safety Board

· (OSHA) Occupational Safety and Health

· (PA) Privacy Act

· (QC) Quality Control

· (QA) Quality Assurance

· (SOW) Statement of Work

ATTACHMENT 1

Ad hoc – Additional items that may be funded as an add-on option or separate contract

RNA Sequencing of Tissues Another series of biological samples (e.g., heart, lung, liver, muscle, brain) may be extracted for RNA by the Functional Genomics team, and the resulting RNA (or RNA libraries prepared in house by the Functional Genomics team) shipped to the Contractor for sequencing. Library preparation and/or sequencing may be outsourced to the Contractor as another add-on option or separate contract. For such an add-on option or separate Contract, the Contractor must provide evidence of experience with and capacity for sequencing low quantity and low quality RNA.

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