Amendment_2.pdf

(x)

NHLBI-CSB-HV-2016-36-JS

x x

4 copies of the amendment; (b) By acknowledging receipt of this amendment on each copy of the offer submitted ; or (c) By separate letter or telegram which includes a reference to the solicitation and amendment numbers. FAILURE OF YOUR ACKNOWLEDGEMENT TO BE RECEIVED AT

THE PLACE DESIGNATED FOR THE RECEIPT OF OFFERS PRIOR TO THE HOUR AND DATE SPECIFIED MAY RESULT IN REJECTION OF YOUR OFFER. If by virtue of this amendment you desire to change an offer already submitted , such change may be made by telegram or letter, provided each telegram or letter makes reference to the solicitation and this amendment, and is received prior to the opening hour and date specified.

x

ADM-NHLBI

Bethesda MD 20892-7511 Institute National, Heart, Lung and Blood National Institutes of Health

IO-NHLBI

Bethesda MD 20892-7511 Institutes National Heart, Lung, and Blood National Institutes of Health

04/28/2016000002

13. THIS ITEM ONLY APPLIES TO MODIFICATION OF CONTRACTS/ORDERS. IT MODIFIES THE CONTRACT/ORDER NO. AS DESCRIBED IN ITEM 14.

12. ACCOUNTING AND APPROPRIATION DATA (If required) is not extended.is extended, Items 8 and 15, and returning

Offers must acknowledge receipt of this amendment prior to the hour and date specified in the solicitation or as amended , by one of the following methods: (a) By completing

The above numbered solicitation is amended as set forth in Item 14. The hour and date specified for receipt of Offers

11. THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS

FACILITY CODE CODE

10B. DATED (SEE ITEM 13)

10A. MODIFICATION OF CONTRACT/ORDER NO.

9B. DATED (SEE ITEM 11)

9A. AMENDMENT OF SOLICITATION NO.

CODE

8. NAME AND ADDRESS OF CONTRACTOR (No., street, county, State and ZIP Code)

7. ADMINISTERED BY (If other than Item 6)CODE 6. ISSUED BY

PAGE OF PAGES

4. REQUISITION/PURCHASE REQ. NO.3. EFFECTIVE DATE2. AMENDMENT/MODIFICATION NO. 5. PROJECT NO. (If applicable)

1. CONTRACT ID CODE

AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT

04/28/2016

CHECK ONE A. THIS CHANGE ORDER IS ISSUED PURSUANT TO: (Specify authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE CONTRACT

B. THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying office, C. THIS SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO AUTHORITY OF:

D. OTHER (Specify type of modification and authority) appropriation date, etc.) SET FORTH IN ITEM 14, PURSUANT TO THE AUTHORITY OF FAR 43.103(b).

E. IMPORTANT: Contractor is not, is required to sign this document and return __________________ copies to the issuing office.

ORDER NO. IN ITEM 10A.

14. DESCRIPTION OF AMENDMENT/MODIFICATION (Organized by UCF section headings, including solicitation/contract subject matter where feasible.)

The solicitation is amended as set forth below. THE HOUR AND THE DATE SPECIFIED FOR

RECEIPT OF PROPOSALS IS EXTENDED TO JUNE 8, 2016 AT 2PM EDT.

All other terms and conditions of the solicitation remain unchanged.

DESCRIPTION OF AMENDMENT:

PURPOSE: To update the statement of work and sample task orders and to provide responses to the submitted questions.

The revised documents and responses to questions are attached to the amendment. Additions

Continued ...

16A. NAME AND TITLE OF CONTRACTING OFFICER (Type or print)15A. NAME AND TITLE OF SIGNER (Type or print)

15C. DATE SIGNED 16B. UNITED STATES OF AMERICA 15B. CONTRACTOR/OFFEROR 16C. DATE SIGNED

(Signature of person authorized to sign) (Signature of Contracting Officer)

Jennifer E. Swift

STANDARD FORM 30 (REV. 10-83)

Prescribed by GSA

FAR (48 CFR) 53.243

NSN 7540-01-152-8070

Previous edition unusable

Except as provided herein, all terms and conditions of the document referenced in Item 9 A or 10A, as heretofore changed, remains unchanged and in full force and effect .

ITEM NO. SUPPLIES/SERVICES QUANTITY UNIT UNIT PRICE AMOUNT

NAME OF OFFEROR OR CONTRACTOR

2 2

CONTINUATION SHEET

REFERENCE NO. OF DOCUMENT BEING CONTINUED PAGE OF

(A) (B) (C) (D) (E) (F)

NHLBI-CSB-HV-2016-36-JS/000002

to the RFP, include Note #4.1 of the General

Tasks and changes to technical specifications

(including Note 3) within Sample Task #2: Whole

Genome Sequencing and within Sample Task #4: RNA

Transcriptome Sequence Profiles.

NSN 7540-01-152-8067 OPTIONAL FORM 336 (4-86)

Sponsored by GSA

FAR (48 CFR) 53.110

Attachment 1 - Questions and Answers

General Business and Formatting Questions:

1. Please confirm if all subcontractor information should appear in both the General Task Area Proposal and each Specific Task order Answer: The subcontractor information that should be included in the General Task Area Proposal is the same as that of the Offeror, i.e. if the offeror is including information in the General Task Area (ex. system security information) the subcontractors information should be included too. The specific Task Area should indicate specific subcontract information as it relates to the specific task.

2. Confirm all “miscellaneous” Business Proposal items only located in General Task Order and not repeated in each specific Task Order.

Answer: The following Business Proposal items must be included in the General Task Order, General Price/Cost List, Small Business Subcontracting Plan, Mentor-Protégé Program, HUBZone Small Business Concerns, Total Compensation Plan, Other Administrative Data, Qualifications of the Offeror, Subcontractors, Proposer’s Annual Financial Report, Travel Costs/Travel Policy, Past Performance, and Information Systems Security (if applicable). Only the budget for the specific task should be included in the business proposal for the specific task area.

3. Confirm “Roster of Employees requiring Suitability Investigation” for Level 1 approval required for Tasks 3-6.

Answer: Per Article C.2.c. Other Reports/Deliverables, Roster of Employees Requiring Suitability Investigations is a deliverable for Task 2 only.

4. Pertinent to Personnel requirements on pp.80-83, are Letters of Commitment for subcontract personnel (and investigators who are not employed by the offeror), or does institutional LOI suffice?

Answer: An Institutional Letter of Intent is sufficient for subcontractors.

5. Please clarify procedures for responding to task orders once a contract is received – is an additional proposal required? See item (a.1) on p.60 Answer: After award and as requirements are needed, all contractors who received an IDIQ contract will receive a request for task order proposal for the work to be completed.

6. Are separate CD copies needed for each task area proposed, or should we provide one CD containing all technical documentation and one for all business documentation?

Answer: All task area proposals must be included within the offerors proposal. The entire technical proposal (inclusive of all sample task orders) must be included on one disk. The same applies to the business proposal. If there is enough space for the technical and business proposal to be on one disk, the offeror may submit one disk with the technical and business proposal provided they are separate files.

7. Please confirm if submissions to only one or two of the task areas are acceptable or all task areas need to be met by the same vendor in order to submit a proposal.

Answer: All offerors must submit a proposal for Task Area 1: Manual of Operations, and AT LEAST one other task area. Offerors need not apply for all task areas contained within the solicitation.

8. So that we can plan appropriately for overall program coordination, we would like clarification of the reporting requirements. Pages 7, 8, and 9 of the solicitation (PDF pages 14, 15, and 16) state bi-weekly reporting requirements for Task Orders 3, 4, 5, and 6. Are the reports for these TOs due every two weeks or twice a week?

Answer: Bi-weekly reports are due every two weeks.

9. Item number 6 on page 64 of the solicitation (PDF page 71) refers to the “substudy of the proposal section of the Technical Plan” and states that the substudy is limited to eight pages of the 30-page technical proposal. What is the substudy?

Answer: This program does not include a substudy and therefore, the 8 pages for the substudy does not apply.

10. Item #5 on page 78 of the solicitation (PDF page 85) states that, “This acquisition requires Contractor to host an NIH webpage or database,” and the solicitation requires the Contractor to conduct periodic vulnerability scans and report on the scans monthly. Can you clarify what “NIH webpage or database” is being hosted and/or proposed in the solicitation?

Answer: An NIH webpage or database is not applicable to this solicitation; however, the language is standard language for the clause. Vulnerability Scans are required for Task Area 2 only.

11. What is the product for which Form 508 is required?

Answer: 508 applies to all reports and deliverables. Please review the information provided within the solicitation and at http://www.hhs.gov/web/508/contracting/technology/vendors.html for its applicability.

12. Can a revised version of the NIH biosketch format be used in place of resume for key personnel?

It contains the same information requested for the resume (i.e., educational background, recent experience, specific or technical accomplishments, and a listing of relevant publications) in a much more concise manner.

Answer: Provided the revised Biosketch includes all required information and meets the page limits, it may be used in place of a resume.

13. Page 95 of the solicitation (PDF page 102), Adequate Accounting System, states that contract will NOT be firm-fixed price; however, it is expected to be firm-fixed price. Can you please clarify?

Answer: While Offerors are proposing fixed price tasks for the IDIQ, there is a possibility for cost reimbursement task orders in the future. As such, Offerors are required to include the information identified under “Adequate Accounting System” in their proposal.

14. If a vendor is subcontractor in a proposal submitted under this solicitation, can they also submit their own proposal?

Answer: Yes. If a vendor is a subcontractor, they can also submit their own proposal as long as it is substantially different from the proposal in which they are a subcontractor.

http://www.hhs.gov/web/508/contracting/technology/vendors.html

Technical Questions:

General Task # 1

1. The SOP, I understand needs to be finalized soon after the contract is awarded. However for the application itself, is a draft SOP required in the technical report? I assume so but wanted to check.

Answer: We presume the SOP being referred to is the Manual of Operations. When submitting a proposal, the offeror must include the necessary information to determine whether they understand the requirement. The manual of operations itself is due within one month from the date of award of the task order.

General Task # 4

1. Task Order Description/Statement of Work

Please provide additional information/clarification about the following items in the RFP on Attachment 11, under the section B. Task Order Description/Statement of Work

1. # 3 Provide read lengths of at least 150 bp (minimum read depth 5-15x) to minimize error reads and enable more complete transcriptome assembly.

1. Is the minimum required read length 2X 150 bp, or 2 x 75 bp?

2. Considering the dynamic range of transcript expression in a sample, is the stated required read depth in reference to the average read depth of all transcripts combined, or does it relate to any transcript (lowest 1000 expressed) in a sample?

Answer: Provide read lengths of 101 bp paired-end reads (with options priced for 30, 40, and 50 million reads) to minimize error reads and enable more complete transcriptome assembly.

2. # 5 Utilize libraries that enable both small and long RNA species detection

1. In order to fulfil this requirement and obtain all transcripts (coding as well as non-coding) that are of at least 150 bp, we would need to sequence these libraries twice as deep compared to the PolyA+ enriched libraries to generate similar transcript depth. This would double the cost of the sequencing.

Therefore, we would like your feedback on this requirement to understand if our interpretation of this task aligns with the RFP requirement.

Answer: Utilize libraries that efficiently enable small (ncRNAs) and long (mRNA) RNA species detection. If the inclusion of ncRNAs (including miRNAs) leads to higher costs, exclude them from the proposal

Answer: To clarify these questions, items #3 and #5 have been rewritten and the request for sample task order proposal for Task 4: RNA Transcriptome has been revised and attached to the amendment.

2. Can you clarify what is meant by a minimum read depth of 5-15x for Task Area 4 in Attachment

11 (PDF page 155)? It is not clear what is meant by minimum read depth of 5-15x as this is dependent on the complexity of the transcriptome of the tissue being tested. Typically, one requests X millions of reads per library at a specific read length for this type of analysis.

Answer: For clarification, we are setting a standard of 101 PE x and requesting bids covering 30, 40, and 50 million reads. Indicate the cost at each read level, as appropriate.

3. Technical Evaluation Criteria for Task 4 states:

RNA transcriptome sequence methodology and throughput (30pts.)

Adequacy of the proposed approach to provide the workflow needed for RNA transcriptome sequence analysis: e.g. raw data QC, preprocessing, peak feature mapping, post-alignment processing, annotation, and prioritization. Provide a flow-chart, operational criteria, and versioning for listed tools or reference builds and standards.

Could you please clarify the types of data expected for peak feature mapping and prioritization in the context of RNASeq analysis?

Answer: Peak feature mapping may include but is not limited to determining a peak in the sequencing coverage in an intergenic region, or identifying and classifying small or 5' cap RNA sequencing data. Indicate if your workflow examines these issues or is needed by your protocol.

Variant detection from massive parallel sequencing data includes two steps. Following variant calling, variant prioritization and filtering is used to obtain reliable variants of high confidence.

Prioritization may include but is not limited to prioritization of RNAseq data for post-hoc analysis based on absolute changes in transcript abundance. It may also include variant quality score recalibration such as VQSR, SNPiR, and RVboost. Indicate if and how your workflow examines these or other prioritization issues.

General Task # 6

1. If we have two different proteomics methods that would be appropriate for analyzing 1000 samples per year can these be combined together in a single application? In other words, we would have both methods described with their QC etc. in the 30 pages of the technical report?

Answer: Yes, however offerors will be limited to the page limit of 30 pages per task area to discuss both methods. If you have more than one method you’d like to propose – include them in the same proposal. Do not submit two separate proposals. Make sure that the cost for each method is clearly documented.

2. For task 6, how much data analysis should be included. Should we include data to knowledge (level 3 informatics) or only level 1 (protein identification) and level 2 (protein quantification)?

Answer: Level 3 is preferred. Offeror should provide clear pricing for a) level 1 and 2, and b) level 1-3.

Budget Questions:

1. Attachment 19 – Cost Detail for Business proposal. Is this form required or are other excel formats with equivalent detail allowable?

Answer: This document is not required for firm fixed price tasks and other formats are acceptable. This document is a sample for cost reimbursement budgets and not required;

however a cost reimbursement budget must include this information.

2. Total Compensation Table:

a. Should this reflect 100% salary or FTE % for project?

Answer: This should reflect the FTE for the project

b. True salary (above cap) or proposal salary? See item (b.1) on p.93

Answer: This should reflect the personnel’s salary unless it exceeds the salary cap.

3. Is a detailed budget required for all 5 years of the RFP, or year 1 (period of performance) only?

Answer: A detailed budget should reflect the period of performance for the specific task in which is being proposed. A general budget for all five years should be included in the general budget proposal.

4. Is the maximum capacity intended to reflect that of the 12 month performance period, or a maximum over 5 years of the contract?

Answer: The maximum capacity should reflect the maximum capacity for the offeror each year over the five year period.

5. For cost per task, I want to make sure that it is cost per assay. If we do each sample in duplicate should the cost reflect that as 2x assay. In addition, if we expect 20% redo, which happens if the sample does not reach a CV% of 20% or less. Should we put that cost into the cost per assay?

Answer: Cost per task when referenced in the specific task area, refers to the total cost per task area, not per assay, but the cost to complete the entire task area (as defined in the sample task order). Pricing should be proposed in a manner that allows for a price reasonableness determination.

6. With respect to equipment – can we request funds for renting or purchasing equipment in order to increase capacity of our method? If so, what would be required as justification and proof of cost? Or would we just put that cost within the price of each assay?

Answer: All Offerors must have the necessary equipment in order to complete the task areas awarded. Equipment will be an unallowable expense under these contracts.

7. Based on the example outline and solicitation instructions, we will include each Sample Task Order Proposal within the General Technical Proposal including the technical proposal and business proposal (i.e., detailed budget for firm fixed-price breakdown and supporting price documentation) for each Sample Task Order Proposal. Should we also include the detailed budget for each Sample Task Order Proposal in the General Business Proposal?

Answer: The technical proposal for each specific task should be included under the general technical proposal and the business proposal (detailed budget) for the specific task should be included under the general business proposal.

ATTACHMENT 3

January 20, 2016 Page 1 of 5

STATEMENT OF WORK

TITLE: Centralized Omics Resource (CORE) for TOPMed

BACKGROUND

National Heart, Lung, and Blood Institute’s (NHLBI) Centralized Omics REsource (CORE) contract program provides whole genome sequencing and other Omics measures including DNA methylation, RNA expression patterns, metabolic profiling, and other novel omics for use with other phenotype and clinical outcome data from studies focused on heart, lung, blood and sleep (HLBS) disorders. Thus the program as part of NHLBI's Trans-Omics for Precision Medicine (TOPMed) Program, seeks to discover factors that influence disease risk, identify subtypes of disease, and develop more targeted and personalized treatments. In addition to providing a comprehensive view of genetic, molecular, and cellular architecture, the unprecedented rich data resource generated by CORE will be available to the scientific community stimulating innovative approaches to examine novel questions to address HLBS disorders.

OBJECTIVE

An Indefinite Delivery, Indefinite Quantity (IDIQ) contract mechanism will be utilized to support CORE. The objective of the CORE contract program is to generate Omics data for studies selected by NHLBI for participation in TOPMed. Omics technologies include Large Scale WGS, DNA Methylation, RNA Sequencing, Metabolic Profiling, and Novel Omics Technologies.

SCOPE

Independently, and not as an agent of the Government, the Contractor must furnish all necessary labor, materials, supplies, equipment, and services (except as otherwise specified herein) and perform the work set forth below.

The scope of this IDIQ contract program will cover multiple Omics approaches for selected TOPMed studies as follows.

[Note 1 to Offerors: The Indefinite Delivery, Indefinite Quantity (IDIQ) contract mechanism will fulfill NHLBI’s requirement of recurring needs, when the government cannot predetermine the precise quantity that will be required during the contract period, nor a specific delivery date. All IDIQ contracts will include a minimum and maximum value. All successful Offerors will receive a task order award under their IDIQ contract for the “minimum” award value based on the requirement described in “General Task 1” below. A maximum value will be stated in each IDIQ contract at time of award based on the recurring needs for “General Task 2, General Task 3, General Task 4, General Task 5, and General 6,” however, the government is only required to award the “minimum” award value, and based on recurring needs, may obligate up to the maximum value defined in the contract.]

ATTACHMENT 3 - Statement of Work

January 20, 2016 Page 2 of 5

[Note 2 to Offerors: Offerors must propose on “General Task No. 1” and any of the General Tasks that they wish to provide services to the Government for, as well as the Associated Sample Tasks. The associated sample tasks are identified below. Sample tasks may or may not reflect a firm requirement of the NHLBI. Offerors will be evaluated on each General Task (and its respective Sample Task) area independently. Offerors who submit a proposal in response to General Task 6 (Novel Omics Profiles) need not submit for all areas under that task. Each area, within this general task area will be evaluated as a stand-alone area.]

[Note 3 to Offerors: Partnerships are not required. All potential Offerors who believe they have the capability to meet the requirement of the statement of work may submit a proposal in response to this solicitation, whether as a partnership or standalone.]

[Note 4 to Offerors: The Government will identify the studies, trials, or cohorts that will provide the samples required for each Task.]

[Note 4.1 to Offerors: As an aid to evaluation, Offerors are encouraged to also indicate the data formats included in their proposals using The Cancer Genome Atlas Data Levels and Data Types ( https://tcga-data.nci.nih.gov/tcga/tcgaDataType.jsp ). Use the data levels appropriate to the methodology. For those not listed, or if data goes beyond that indicated, you may indicate data at levels 1-4 and relevant metadata ( https://wiki.nci.nih.gov/display/TCGA/Data+level ) .]

GENERAL TASK 1: Generate a Manual of Operations

This task requires the contractor to generate one (1) Manual of Operations specific to all Tasks in which the contractor is proposing services to the Government. They include: General Task 2:

Large Scale WGS; General Task 3: DNA Methylation; General Task 4: RNA Sequencing; General Task 5: Metabolic Profiling; and General Task 6: Novel Omics Technologies. The Manual of Operations will be reviewed annually and, should there be a change in technique, a Task Order will be issued for the revision of the Manual of Operations. The stated award to successful Offerors for this Task represents the “minimum” and is $1,000.

[Note 5 to Offerors: For example, if an Offeror receives an IDIQ contract for General Tasks 1, 2, and 3, the contractor shall provide one (1) Manual of Operations which will include both a Manual of Operations for Large Scale WGS and DNA Methylation. The amount awarded to successful contractors will not exceed $1,000, regardless of the number of Tasks addressed.]

GENERAL TASK 2: Whole Genome Sequencing for 5,000 samples up to maximum capacity (to be proposed in increments of 5,000)

This task requires obtaining large scale, high throughput Whole Genome sequencing from NHLBI selected studies. WGS must include sufficient read lengths and coverage to allow for successful rare variant detection. DNA will be provided from either blood (preferred) or cell lines. WGS data, following cleaning, QC/QA, and assembly must be securely transmitted to https://tcga-data.nci.nih.gov/tcga/tcgaDataType.jsp https://wiki.nci.nih.gov/display/TCGA/Data+level

January 20, 2016 Page 3 of 5

NHLBI designated partners. In addition to the above, task order contractors must participate in TOPMed in-person meetings and conference calls dealing with data integration, formats, QC/QA and others designated by NHLBI.

When promising technologies are identified and has been requested by the COR, the contractor shall prepare a technology evaluation proposal.

GENERAL TASK 3: DNA Methylation Profiles for 1,000 samples up to maximum capacity (to be proposed in increments of 1,000)

This task requires obtaining whole genome methylation and/or hydroxymethylation data profiles from NHLBI selected studies. Data can be generated by array and/or sequencing technologies. Array based techniques must investigate sufficient CpG sites to provide sufficient coverage for the determination of transcriptional control. Sequencing approaches must include sequencing depth and read lengths for fine detail mapping of CpG sites. DNA will be provided from blood (preferred), tissue, and/or cell lines. Methylation profile data (raw, processed, and segmented/interpreted), following cleaning, QC/QA, and assembly will be securely transmitted to NHLBI designated partners. In addition to the above, task order contractors must participate in TOPMed in-person meetings and conference calls dealing with data integration, formats, QC/QA and others designated by NHLBI.

When promising technologies are identified and has been requested by the COR, the contractor shall prepare a technology evaluation proposal.

GENERAL TASK 4: RNA Transcriptome Sequence Profiles for 1,000 samples up to maximum capacity (to be proposed in increments of 1,000)

This task requires obtaining state of the art RNA transcriptome sequence profiles from NHLBI selected studies. Sequencing approaches must include sufficient sequencing depth and read lengths for complete transcriptome assembly. RNA may be provided from blood (preferred), tissue, and/or cell lines. Library preparation must enable both small and long RNA species detection. RNA sequence profile data (raw, processed, and segmented/interpreted), following cleaning, QC/QA, and assembly must be securely transmitted to NHLBI designated partners. In addition to the above, task order contractors must participate in TOPMed in-person meetings and conference calls dealing with data integration, formats, QC/QA and others designated by

NHLBI.

When promising technologies are identified and has been requested by the COR, the contractor shall prepare a technology evaluation proposal.

GENERAL TASK 5: Metabolite Profiles for 1,000 samples up to maximum capacity (to be proposed in increments of 1,000)

This task requires obtaining targeted and non-targeted metabolite profiles from NHLBI selected

January 20, 2016 Page 4 of 5 studies. Metabolite profiling approaches will provide robust metabolite identification, include broad coverage of the metabolome (including key metabolic pathways), and the use of authentic standards for targeted profiles. Starting materials may be provided from blood (preferred), tissue, and/or cell lines. Library preparation will enable both small and long RNA species detection. Metabolite profile data (raw, processed, transformed, and final transformed), following cleaning, QC/QA, and assembly will be securely transmitted to NHLBI designated partners. In addition to the above, task order contractors must participate in TOPMed in-person meetings and conference calls dealing with data integration, formats, QC/QA and others designated by NHLBI.

When promising technologies are identified and has been requested by the COR, the contractor shall prepare a technology evaluation proposal.

GENERAL TASK 6: Novel Omics Profiles for 1,000 samples up to maximum capacity (to be proposed in increments of 1,000)

This task requires obtaining Omics technologies that are novel to the TOPMed program.

Measures can include any changes in cell state whether transitory, permanent, or mutable.

Approaches may include but are not limited to: a) total RNA sequencing, b) non-coding RNA sequencing, c) SNP identification/replication, d) DNaseI hypersensitivity, chromatin and/or histone interaction epigenomic assays, e) metagenomics, and/or f) proteomics. Starting materials may be provided from blood (preferred), tissue, and/or cell lines. Novel Omics profile data (raw, processed, segmented/interpreted data, and region of interest data), following cleaning, QC/QA, and assembly must be securely transmitted to NHLBI designated partners. In addition to the above, task order contractors must participate in TOPMed in-person meetings and conference calls dealing with data integration, formats, QC/QA and others designated by NHLBI.

When promising technologies are identified and has been requested by the COR, the contractor shall prepare a technology evaluation proposal.

[Note 6 to Offerors: For proposal evaluation purposes, the technical evaluation team will evaluate the offeror’s capability to perform the requirements described above for General Tasks 1, 2, 3, 4, 5, and 6. The offerors overall large scale production capacity will be evaluated in terms of operating as a contractor that has the capability to support the identified tasks in the contractors proposal and the contractors minimum and maximum quantities.

[Note 7 to Offerors: Anticipated Sample Task Orders No. 2 through 6 described are included as separate attachments and identify the current anticipated firm requirements. The technical evaluation team will also review and evaluate the “Anticipated Sample Task Orders” and these will potentially be awarded by September 2016. Please note that successful contractors will only be guaranteed an award for a minimum amount (described in General Task 1) and will not necessarily be awarded the Sample Task Orders described in the attachments.]

January 20, 2016 Page 5 of 5

[Note 8 to Offerors: Offerors shall provide a brief description of the projects, methods, and any resulting publications.]

[Note 9 to Offerors: Offerors shall provide a brief description of the technology and protocols used for each Task.]

[Note 10 to Offerors: Anticipate a one-month period of performance for Task 1. Anticipate a twelve-month period of performance for Tasks 2-6.]

The Contractor shall prepare 508-compliant versions of all electronic data deliverables (e.g.

documentation materials, systems, databases, websites and/or customized software applications) that are to be posted online or electronic copies to be distributed publicly or to Federal employees.

[Note 11 to Offerors: The Offeror’s proposal must demonstrate compliance with the "Electronic and Information Technology Accessibility Provisions" set forth by the Architectural and Transportation Barriers Compliance Board (also referred to as the "Access Board") in 36 CFR part 1194 for all electronic and information technology (EIT) products and services developed, acquired, maintained, or used under this contract/order, including EIT deliverables such as electronic documents and reports.

[NOTE: Parts of Section 508 of the Rehabilitation Act are determined as applicable to the deliverables of this task. The requirements include, but may not be limited to the following subsections of 508:

• 1194.31 Functional Performance Criteria (a-f)

• 1194.41 Information, Documentation, and Support (a-c)

Upon the request from the NHLBI COR, the Contractor shall supply a 508 Test Plan which should include test cases for all applicable provisions, test methods (imperative that a combination of automated and manual methods are utilized) and test results for delivered materials.]

ATTACHMENT 9

NOTE TO OFFERORS: This sample task order is for evaluation purposes only and may or may not be issued at time of award.

SAMPLE TASK ORDER (TO)

REQUEST FOR PROPOSAL

Task Area Two (2)

Contractor: ____________________ Contract No: TBD Task Order No. TBD Modification No: N/A TO Title: TBD Project Officer: TBD Date Prepared: _________________ Contract Task Area: 2: Whole Genome Sequencing for 5,000 samples up to maximum capacity (to be proposed in increments of 1,000)

REQUEST FOR TO PROPOSAL RELEVANT INFORMATION

A. Period of Performance: Twelve (12) months from time of award.

B. Task Order Description / Statement of Work:

1) Provide at a minimum whole genome sequencing (WGS) using Illumina HiSeq X Ten platform with mean mappable coverage >30x with the following baseline criteria:

a. Read groups that identify project sample identifiers, libraries, sequencing center and sequencing lane

b. 90% of genome covered at 20x, 95% at 10x, with a contamination rate of <1%

c. Minimum of 86 x 10^9 mapped, aligned bases with Q20 or higher, with minimum coverage calculated after duplicate removal

d. Minimum read length of 100 bp, paired end

e. No filtering of low quality, unmapped, or duplicate reads [reads with too few Q20 and large fraction of N bases may be filtered]

f. Data delivered in CRAM format (optimally) or BAM files with binned 8-bit qualities and no optional quality tags (avoid OQ, BD, BI)

NOTE # 1 TO OFFERORS:

Offerors are requested to propose additional pricing for samples requiring PCR amplification on a per sample bases if not included in the baseline.

NOTE # 2 TO OFFERORS: Offerors are requested to provide a separate optional line price for CRAM format and/or BAM squeeze (if it is not already included as part of the base price)

g. Provide sequential Just In Time secured/encrypted transfer of sequence data to the

NHLBI designated repository(ies):

NOTE # 3 to Offerors:

Provide a separate optional line price for WGS (if not already included as part of the base price) with additional post-sequencing processing beyond that designated as “baseline criteria”. Indicate pricing for the generation of VCF (preferred), gVCF, and VCF plus gVCF:

h. Data mapped to hs38DH decoy reference (or equivalently GRCh38_full_analysis_set_plus_decoy_hla) using BWA-MEM (version 0.7.13) or newer

i. Incorporate dbSNP build 147 for recalibration

j. VCF 4.2 format or higher with corresponding TOPMed optional gVCF

k. Provide correct and complete .xml meta data for submission to the NCBI Sequence

Read Archive

2) Utilize state of the art computational tools and algorithms for WGS analysis

3) Provide data cleaning, including but not limited to checks for Hardy-Weinberg equilibrium, Mendelian inconsistencies (in families), visualization of base quality scores and nucleotide distributions, trimming of reads and read filtering based on base quality score and sequence properties such as primer contaminations, N content and GC bias

4) Provide personnel with expertise and experience in high throughput large-scale WGS, general laboratory management, and quality control (QC) (used here and throughout encompassing quality assurance and quality control activities)

5) Provide personnel with expertise and experience in DNA preparation, aliquotting, labeling, whole genome amplification, shipping, and minimum acceptable standards for DNA quantity and quality for samples submitted for whole genome sequencing

6) Provide personnel with expertise and experience in sample receipt, tracking, handling and storage, including the use of an in-house Laboratory Information Management System (LIMS); develop and implement procedures for these activities

7) Provider must use seamless LIMS for contracted production and must provide real-time tracking by all production partners and this information must be available in real-time between production partners. NHLBI must have the ability to identify where a sample is in production via communications

8) Provide capabilities for sample randomization. Randomization must meet minimum of

NHLBI’s TOPMed standards: The offeror will randomize each study’s samples (both cases and controls; also cohort samples) robotically to randomize the order in which samples are processed. This will be completed within each of a small number of large batches of samples. Larger batches are preferred, ideally just one batch per study where this is possible. In family studies, the unit of randomization will be families, rather than individuals, in order to keep family members together as they move through the process.

9) Provide personnel with expertise and experience in genetic analyses and bioinformatics for data cleaning

10) Provide personnel with expertise and experience in the secure physical and electronic transfer of large-quantities of genetic data as well as securing in-house data

11) Provide raw data and final WGS data to the Project Office or its designee on request in a complete and timely manner

12) Provide a Final Manual of Operations within 30 days of task order initiation. Details in

Reporting Requirements

13) Provide weekly Status Reports to the NHLBI Project Office and designated committees. The weekly Status Report shall summarize the status of the sequencing, the weekly QC data, the weekly production, completeness, and quality metrics. Details are given in the Reporting Requirements

14) Communicate with NHLBI’s designated Data Coordinating Center (DCC), and the respective

NHLBI designated studies to coordinate DNA and sample delivery and de-identified sample study information (e.g. Study Participant ID, Study Sample ID, and Gender)

15) Communicate with NHLBI’s designated Informatics Research Center (IRC) and/or NCBI to coordinate WGS data delivery to dbGaP

16) Provide materials and information promptly and communicate with the Program Office, NHLBI designated studies, DCC, and IRC frequently and regularly

17) Maintain the confidentiality of the data received, produced, and distributed and to adhere to information technology practices in all aspects of data management to assure that only authorized individuals can gain access to the sequence data

18) Maintain security guidelines that meet or exceed the current dbGaP Security Best Practices, including its detailed description of requirements for security and encryption http://www.ncbi.nlm.nih.gov/projects/gap/pdf/dbgap_2b_security_procedures.pdf.

In addition, this includes, but is not limited to:

a. all approved users have completed all required institutional computer security training, e.g. http://irtsectraining.nih.gov/, or the equivalent

b. the data will always be physically secured (e.g. through camera surveillance, locks on doors/computers, security guard)

c. servers must not be accessible directly from the internet (i.e. must be behind a firewall or not connected to a larger network), and unnecessary services disabled

d. use of portable media, e.g., on a CD, flash drive or laptop, is discouraged; if necessary then they must be encrypted

e. updated anti-virus/anti-spyware/anti-malware software

f. security auditing/intrusion detection software, detection and regular scans of potential data intrusions

g. strong password for file access and never share it

h. All copies of the dataset must be destroyed whenever NHLBI requests destruction of the dataset

19) Provide secure backup of all data essential to the project, including but not limited to all sequencing data generated (including raw data), study data received, sample tracking and storage information, and QC information

20) Provide shipping and handling of DNA and related samples to and from the NHLBI designated DNA repositories. Bar-coded DNA sample arrays will be provided without charge.

Offeror will provide best practices for sample concentration and plating and will initiate pilot QC testing of study DNA within 7 days of task order initiation.

21) Receive and process data and samples from NHLBI designated studies, including:

a. Verify and obtain records of Institutional Review Board approval(s) for the study prior to accepting samples for sequencing

b. Receive, track, and store DNA and other samples and accompanying data from NHLBI designated studies in preparation for sequencing

NOTE # 4 TO OFFERORS:

Offerors are strongly encouraged to contact local IRBs in advance. If delays are expected, amended timetables should be part of the submission.

22) Pilot QC of representative study DNA samples within 7 days of the start of the task order period

23) Initiate and deliver sequencing data of the initial 150 NHLBI designated samples received and an TOPMed controls as designated by NHLBI within the first 10 weeks (30 days for sample receipt, 6 weeks for sequencing completion and delivery to NHLBI and designees) of task order award for review by NHLBI and designees.

NOTE # 5 TO OFFERORS:

Offerors should deliver and price sequencing data to include the additional TOPMed controls as a part of the overall proposal. TOPMed Controls are designated as a specific HapMap PUR trio and a CEU and YRI samples at the start of the task, and then alternating between CEU and YRI every 1,000 samples.

24) Following review and authorization of initial samples by NHLBI and designees, complete a minimum overall capacity of 150 genomes per week during production and provide a schedule for completion

25) Complete sequencing and electronic delivery of appropriately cleaned and formatted data from all samples received (including quality control measures during production to identify sequencing errors and sample mix-ups) by end of task order period (12 months). Quality control methods should include appropriate controls. See technical acceptability criteria in item 1 above.

NOTE # 6 TO OFFERORS:

Offerors are asked to include recommendations on suggested controls during production and the impact on project costs should be clarified in the initial response and during the contracted production period. Sequencing a set of well-characterized samples (such as a subset of 1000 Genomes Project samples or an NHLBI designated set of samples, potentially including a small nuclear family) is an appropriate positive control for sequencing. In fact, TOPMed includes a baseline sample of 1000 Genome Samples and trios (see Statement of Work for WGS, Item 23). Offerors are not asked to change their standard positive controls but are expected to add these to their production. It is recommended that applicants follow good laboratory practices to monitor the quality of their processes and results. These might include (but are not limited to or required) generating data for a subset of variants and/or samples using an orthogonal technology that might enable results to be validated (this might include targeted sequencing using long reads (e.g. PacBio or Sanger methods or genotyping using a common variant array) and that this data should allow both confirmation of a subset of variant genotypes as well as subset of reference calls. Other processes that monitor and help ensure, for example, separation of pre- and post-PCR areas in the lab may also be recommended. Negative controls for detection of contaminants are among the negative controls that could be incorporated. Offerors should indicate the positive and negative controls incorporated during production and when they may be applicable.

26) Perform appropriate QC for quantification, post library prep, on-instrument sequencing and post genome build

27) Transfer sample identifiers including electronic and genetic barcodes; a complete, cleaned data set including CRAM or BAM files meeting TOPMed criteria; and work products for failed genotypes to NCBI and NHLBI by the end of the task order period of performance of the of sequencing initiation pending Contracting Officer Representative (COR) approval

NOTE # 7 TO OFFERORS:

TOPMed considers a sample failed if it doesn't include >95% of the genome covered at 10x and/or an estimated contamination level of >3% with another human sample. Offerors should note if their proposal guidelines improve on this standard.

28) Demonstrated support for completing WGS data at 90 day, 6 months, 9 months, and 1 year.

29) Participate in NHLBI TOPMed designated in person-meetings (1 or 2 during task order performance period expected to be in Bethesda, MD) and conference calls dealing with data integration, formats, QC/QA, data deposition into dbGaP and others as designated by the NHLBI Program Office

30) While the samples to be sequenced have been de-identified, the organization’s Institutional

Review Board (IRB) or equivalent must approve the Contractor for handling human DNA.

Task order employees in contact with human DNA or data derived from these human subjects must provide Certification of Human Subjects Training prior to a task order award.

31) Provide a Draft Final and Final Report according to the details in the Reporting

Requirements

32) When promising sequencing technologies are identified (examples may include changes in cost, increased information or density, or increases in accuracy or interpretation) and has been requested by the COR, the contractor shall prepare a technology evaluation proposal.

C. Deliverables:

See Attached See Deliverables identified in Article F.2., Deliveries (also described in Article C.2.), of the RFP. Although data will not be produced under this sample task order, offerors shall describe their approach for providing all resulting genotyping or sequencing data and associated files to the Investigator and central data repositories.

D. Special Restrictions/Clearances/Clauses: See the following Articles in the RFP.

Article B.3. Advanced Understandings, Section H, and Section I.

E. Evaluation Criteria: See Section M of the RFP. Price is also a factor. The Offeror(s) price proposal will be evaluated for reasonableness. For a price to be reasonable, it must represent a price to the government that a prudent person would pay when consideration is given to prices in the market. Normally, price reasonableness is established through adequate price competition, but may also be determined through cost and price analysis techniques as described in FAR 15.404.

F. Response Due Date: Same date that overall proposal is due (see RFP).

TASK ORDER (TO)

Offerors are reminded that all terms and conditions of the IDIQ contract will apply to all task orders awarded.

Offerors shall submit a separate proposal within the general proposal for this Task Order as listed herein. In doing so, you are to provide a separate Technical Proposal and Cost Proposal (including documentation to support the proposed price).

Technical Proposal

1. Government Furnished Information/Equipment

The Contractor shall provide all necessary equipment for performance of the task order except for the Government furnished information identified in the RFP in Section J – List of Attachments.

2. Deliverables

See deliverable identified Article F.2., Deliveries (also described in Article C.2.), of the RFP.

3. Detailed Description Provide a detailed description of the approach for each task in accordance with the evaluation criteria in Section E above (be specific).

Cost Proposal The Contractor shall attach a detailed budget to identify all proposed costs.

ATTACHMENT 11

NOTE TO OFFERORS: This sample task order is for evaluation purposes only and may or may not be issued at time of award.

SAMPLE TASK ORDER (TO)

Task Area Four (4)

Contractor: ____________________ Contract No: TBD Task Order No. TBD Modification No: N/A TO Title: TBD Project Officer: TBD Date Prepared: _________________ Contract Task Area: 4: RNA Transcriptome Sequence Profiles for 1,000 samples up to maximum capacity (to be proposed in increments of 1,000)

REQUEST FOR TO PROPOSAL RELEVANT INFORMATION

A. Period of Performance: Twelve (12) months from time of award.

B. Task Order Description / Statement of Work:

1) Provide state-of-the art RNA transcriptome sequence (e.g. RNA-seq), profiles for designated NHLBI samples

2) Perform paired-end sequencing to increase mapping accuracy and enhance detection of spliced transcripts

3) Provide read lengths of 101 bp paired-end reads (with options priced for 30, 40, and 50 million reads) to minimize error reads and enable more complete transcriptome assembly;

4) Incorporate quality measures to minimize false discovery rates

5) Utilize libraries that efficiently enable small (ncRNAs) and long (mRNA) RNA species detection. If the inclusion of ncRNAs (including miRNAs) leads to higher costs, exclude them from the proposal;

6) Utilize state of the art computational tools and algorithms for transcriptome identification, quantitation and analysis

7) Provide personnel with expertise and experience in transcriptome profiling, general laboratory management, and quality control (QC) (used here and throughout encompassing quality assurance and quality control activities)

8) Provide personnel with expertise and experience in preparing samples for transcriptome profiling.

9) Provide personnel with expertise and experience in sample receipt, tracking, handling and storage, including the use of an in-house Laboratory Information Management System (LIMS); develop and implement procedures for these activities

10) Provider must use seamless LIMS for contracted production and must provide real-time tracking by all production partners and this information must be available in real-time between production partners. NHLBI must have the ability to identify where a sample is in production via communications.

11) Provide capabilities for sample randomization with a preference for robotic implementation.

Randomization must meet minimum of NHLBI’s TOPMed standards: The offeror will randomize each study’s samples (both cases and controls; also cohort samples) to randomize the order in which samples are processed. This will be done within each of a small number of large batches of samples. Larger batches are preferred, ideally just one batch per study where this is possible. In family studies, the unit of randomization will be families, rather than individuals, in order to keep family members together as they move through the process.

12) Provide personnel with expertise and experience in transcriptome sequence analysis and bioinformatics for data cleaning

13) Provide personnel with expertise and experience in the secure physical and electronic transfer of large-quantities of transcriptome sequence profile data as well as securing in-house data

14) Provide raw data and final sequencing data to the Project Office or its…