Attachment No. 3 SOW BICAN_v 4.4.1.pdf

NIH-NIMH-75N95022R00031 Attachment No. 3

Version 11-30-2016-1 FAR Part 11—Describing Agency Needs

STATEMENT OF WORK (SOW)

GENERAL INFORMATION

Title of Project:

BRAIN Initiative Cell Atlas Network (BICAN) Sequencing Core

Statement of Need and Purpose:

The BRAIN Initiative is creating the BRAIN Initiative Cell Atlas Network (BICAN) to broaden and deepen the systematic cell census and atlas efforts with a new emphasis on the human brain.

The objective of BICAN Sequencing Core is to perform large-scale DNA and RNA sequencing of the libraries. The BICAN Sequencing Core contract program will coordinate and collaborate with researchers funded by BICAN and NIH BRAIN Initiative staff to establish and meet sequencing quality control (QC) metrics, perform requested sequencing tasks, streamline the workflow and process, track sample information, operate in a cost effective and time efficient manner, and ensure data integrity and rapid turnaround. An Indefinite Delivery, Indefinite

Quantity (IDIQ) contract mechanism will be utilized to support the BICAN Sequencing Core.

Background Information and Objective:

Guided by the recommendations of the Advisory Committees to the NIH Director in their BRAIN

2025 and the BRAIN 2.0 reports, the NIH BRAIN Initiative launched a 3-year BRAIN Initiative

Cell Census Consortium (BICCC, 2014-2017), followed by a 5-year BRAIN Initiative Cell

Census Network (BICCN, 2017-2022) to generate a systematic brain cell census in multiple mammalian species. The BRAIN Initiative is now creating the BRAIN Initiative Cell Atlas

Network (BICAN) to broaden and deepen the systematic cell census and atlas efforts with a new emphasis on the human brain. The BICAN will be made up of multiple highly interactive components with complementary roles:

1. Comprehensive Centers on Human and Non-human Primate Brain Cell Atlases (UM1)

(RFA-MH-21-235)

2. Specialized Collaboratories on Human, Non-human Primate, and Mouse Brain Cell

Atlases (U01) (RFA-MH-21-236)

3. Coordinating Unit for Biostatistics, Informatics, and Engagement (CUBIE) (U24) (RFA-

MH-21-237)

4. BRAIN Initiative Data Archives (R24) (RFA-MH-20-600)

5. Scalable Technologies and Tools Projects (R01) (RFA-MH-21-140)

The overarching goal of BICAN is to build reference brain cell atlases that will be widely used throughout the research community, providing a molecular and anatomical foundational framework for the study of brain function and disorders. Thus, the BICAN is expected to characterize all brain cell types (neurons, glia, and other non-neuronal cells) at high-resolution in human, non-human primate, and mouse. The objective of the BICAN Sequencing Core is to perform large-scale DNA and RNA sequencing of libraries generated by BICAN-funded laboratories and to ensure a seamless cloud-based delivery of high quality FASTQ files to an

NIH BRAIN Initiative designated data archive, for use by the research community.

Period of Performance:

This acquisition will be accomplished by a multiple award indefinite delivery / indefinite quantity

(IDIQ) contract with an ordering period and maximum task order period of performance of five years.

SCOPE OF WORK

General Requirements:

Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government as needed to perform the Statement of Work below:

The scope of this IDIQ contract program will cover multiple omics approaches for selected

BICAN studies as follows.

[Note 1 to Offerors: The Indefinite Delivery, Indefinite Quantity (IDIQ) contract mechanism will fulfill the NIH BRAIN Initiative’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 minimum and maximum award values. 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 Area 1” below. A maximum value will be stated in each IDIQ contract at time of award based on the recurring needs for “General Task Area 2, General Task Area

3, General Task Area 4, General Task Area 5, General Task Area 6, and General Task Area

7”; 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.]

[Note 2 to Offerors: In General Task Area 1 and any of the other General Task Areas, Offerors may propose services they wish to provide to the Government, 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 NIH BRAIN Initiative. Offerors will be evaluated on each General Task Area (and its respective Sample Task) independently.]

[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 which will be included when the individual Task Order Request for

Proposals (TORPs) are issued. The samples will be de-identified postmortem human, non-human primate, rodent and other animal samples.]

Specific Requirements:

GENERAL TASK AREA 1: Generate a Manual of Operations

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

• A description of the established sequencing pipeline that includes a list of library types sequenced, a diagram of the operation workflow and timeline, communication plan with library submitters and NIH including time schedules, library QC and pooling, sequencing machines/platforms, laboratory information management system (LIMS), informatics pipeline, data QC and storage, data transfer to external sites/cloud-based data archive(s), process of quality control/assessment/validation of the sequencing pipeline as a whole, and approaches to innovation in sequencing data generation and process to achieve greater scale including anticipated improvements in cost efficiencies throughout the award period.

o The manual of operations shall include a detailed “transfer out” plan. A plan for the transfer of all electronic data, laboratory notebooks, genetic model(s), other biological material, and all laboratory equipment and computers purchased during contract to a successor Contractor and/or storage facility. The detailed plan shall address transition, resource protection and retention, wind down, data transfer and reporting. An updated version of this plan shall be provided upon request to the COR.

o Upon written notice from the CO, the Contractor shall transfer all electronic databases, data management systems, and files as directed by the COR. All data shall be the property of the Government and shall be replicated and disseminated in a transferable format such that any Successor Contractor and

NIMH customers may use the data after transfer.

• General Task 2: Large-Scale Single-Cell Transcriptome Sequencing;

• General Task 3: Large-Scale Single-Cell Epigenome Sequencing;

• General Task 4: Large-Scale Single-Cell Multi-omics Sequencing;

• General Task 5: Bulk Tissue Transcriptome and Epigenome Sequencing;

• General Task 6: Whole Genome and Exome Sequencing; and

• General Task 7: Novel Omics Sequencing.

[Note 5 to Offerors: General Task Area 1 is mandatory. Each Offeror shall respond to

TORP No. 1—the TORP that corresponds with General Task Area 1 Manual of Operations.

The manual of operations will include the general task areas included in the offeror’s proposal.

The performance period for General Task Area 1 is anticipated to be a 1-year base period with four 1-year options and will cover the cost of performance of Task Area 1 throughout the five-year ordering period of the contract. The Manual of Operations will be reviewed annually and, should there be a change in technique, a Task Order modification will be issued for the revision of the Manual of Operations.

Note 5 to Offerors: The Government anticipates awarding a TO under Task Area 1 shortly after award of the IDIQ contract awards. Funding of the option years will be dependent on availability of funds and programmatic need. The Government anticipates this TO will be awarded on a fixed price basis.

GENERAL TASK AREA 2: Large-Scale Single-Cell Transcriptome Sequencing

The task area has two parts: Phase I (pilot study) to establish quality metrics and common agreement on workflows and data pipelines among the BICAN researchers, NIH BRAIN

Initiative staff and the contractors, and Phase II (production) in which the contractor provides large-scale single-cell transcriptome sequencing of libraries provided by BICAN researchers and deposits the data into designated repositories with automated real-time notification to the

Coordinating Unit for Biostatistics, Informatics and Engagement (CUBIE) and NIH staff. It is expected that initial task order will require Phases I and II, and the option period(s) only request

Phase II. The Contracting Officer Representative (COR) will determine which phases are required for the task area.

At the Government’s request, Phase I task requires coordinating and collaborating with other

BICAN researchers, contractors, and NIH BRAIN Initiative staff to establish common quality control/quality assurance (QC/QA) metrics and uniformity of the BICAN sequencing pipelines across different sites. Contractors must describe how they will participate in BICAN in-person meetings and conference calls as well as the pilot studies to develop standard operating procedures within the network of contractors, investigators, and NIH staff. The Sequencing Core contractor will interact with the BICAN labs and other contractors to generate a report that establishes:

(1) a submission and tracking process of the sequencing libraries and the associated metadata,

(2) QC/QA metrics of the sequencing libraries for the large-scale sequencing,

(3) QC/QA metrics of sequencing data, including methods for data cleaning and harmonization,

(4) process and timeline of data transfer to the NIH designated partners/data archive(s),

(5) quality performance uniformity of the sequencing platforms,

(6) results of a pilot study and comparison of the sequencing results across all participating contractors

Phase I will be required for the initial task order request; the performance period for Phase I is anticipated to be 6 months. Phase I may be required for subsequent task orders, at the request of the Government.

Phase II task requires obtaining large-scale, high-throughput sequencing of RNA-seq libraries constructed from single cells, single nuclei, and other minute quantity preparations by BICAN selected studies that use current methods including but not limited to:

1. 10X Genomics Single Cell Multiome Gene Expression or Single Cell 3’ Dual Index Gene

Expression

2. Takara Bio SMART-seq v4

Single-cell or single-nucleus transcriptome sequencing must include sufficient read depth and coverage. The numbers of reads and sequencing cycles are to be finalized during Phase I to allow for successful cell type detection. Single-cell or single-nucleus transcriptome sequencing data, following cleaning, QC/QA, and library demultiplexing must be securely transmitted to NIH

BRAIN Initiative designated partners/data archive(s). The contractor should submit monthly summary reports.

The contractor shall prepare a technology evaluation proposal and conduct a Phase I task study when promising technologies and library types are identified and requested by the Government, which include but are not limited to new 10X Genomics protocols (e.g., Chromium X), sci-RNA-seq, scifi-RNA-seq, smart-seq3, Slide-seq. Phase II task may be adjusted to adopt the new single-cell transcriptomics technologies following the technology validation.

The performance period for General Task Area 2 is anticipated to be six (6) months, with twelve

(12) month option periods over the life of the contract.

[Note 6 to Offerors: Inclusion of at least one of the following: General Task Area 2 or

General Task Area 3 or General Task Area 4, is mandatory]

GENERAL TASK AREA 3: Large-Scale Single-cell Epigenome Sequencing agreement on workflows and data pipelines among the BICAN researchers, NIH BRAIN

Initiative staff and the contractors, and Phase II (production) in which the contractor provides large-scale single-cell epigenome sequencing of libraries provided by BICAN researchers and deposits the data into designated repositories with automated real-time notification to the

Coordinating Unit for Biostatistics, Informatics and Engagement (CUBIE) and NIH staff. It is expected that initial task order will require Phases I and II, and the option period(s) only request

Phase II. The COR will determine which phases are required for the task area.

BICAN researchers, contractors, and NIH BRAIN Initiative staff to establish common QC/QA metrics and uniformity of the BICAN sequencing pipelines across different sites. Contractors must describe how they will participate in BICAN in-person meetings and conference calls as well as the pilot studies to develop standard operating procedures within the network of contractors, investigators and NIH staff. The Sequencing Core contractor will interact with the

BICAN labs and other contractors to generate a report that establishes:

(1) a submission and tracking process of the sequencing libraries and the associated metadata,

(2) QC/QA metrics of the sequencing libraries for the large-scale sequencing,

(3) QC/QA metrics of sequencing data, including methods for data cleaning and harmonization,

(4) process and timeline of data transfer to the NIH designated partners/data archive(s),

(5) quality performance uniformity across the sequencing facilities,

(6) results of a pilot study and comparison of the sequencing results across all participating contractors

Phase I will be required for the initial task order request; the performance period for Phase I is

Phase II task requires obtaining large-scale, high-throughput sequencing of epigenome libraries from single nuclei and other minute quantity preparations by BICAN selected studies that use current methods including but not limited to:

1. 10X Genomics Single Cell Multiome ATAC

2. Single-nuclei methylC-Seq (snmC-seq)

Single-cell epigenome sequencing must include sufficient read depth and coverage. The numbers of reads and sequencing cycles are to be finalized during Phase I to allow for cell type detection. Single-cell epigenome sequencing data, following cleaning, QC/QA, and library demultiplexing must be securely transmitted to NIH BRAIN Initiative designated partners/data archive(s). The contractor should submit monthly summary reports.

The contractor shall prepare a technology evaluation proposal and conduct Phase I task study when promising technologies are identified and requested by the Government, which include but are not limited to sci-ATAC-seq, Hi-C, and ChIP-seq. Phase II task may be adjusted to adopt the new single-cell epigenomics technologies following the technology validation.

The performance period for General Task Area 3 is anticipated to be six (6) months, with twelve

GENERAL TASK AREA 4: Large-Scale Single-Cell Multi-omics Sequencing agreement on workflows and data pipelines among the BICAN researchers, NIH BRAIN

Initiative staff and the contractors, and Phase II (production) in which the contractor provides large-scale single-cell transcriptome sequencing of libraries provided by BICAN researchers and deposits the data into designated repositories with automated real-time notification to the

Coordinating Unit for Biostatistics, Informatics and Engagement (CUBIE) and NIH staff. It is expected that initial task order will require Phases I and II, and the option period(s) only request

Phase II. The Contracting Officer Representative (COR) will determine which phases are required for the task area.

metrics and uniformity of the BICAN sequencing pipelines across different sites. Contractors must describe how they will participate in BICAN in-person meetings and conference calls as well as the pilot studies to develop standard operating procedures within the network of contractors, investigators, and NIH staff. The Sequencing Core contractor will interact with the

BICAN labs and other contractors to generate a report that establishes:

(1) a submission and tracking process of the sequencing libraries and the associated metadata,

(2) QC/QA metrics of the sequencing libraries for the large-scale sequencing,

(3) QC/QA metrics of sequencing data, including methods for data cleaning and harmonization,

(4) process and timeline of data transfer to the NIH designated partners/data archive(s),

(5) quality performance uniformity of the sequencing platforms,

(6) results of a pilot study and comparison of the sequencing results across all participating contractors

Phase I will be required for the initial task order request; the performance period for Phase I is

Phase II task requires obtaining large-scale, high-throughput sequencing of RNA-seq and epigenome libraries constructed from single cells, single nuclei, and other minute quantity preparations by BICAN selected studies that use current methods. including but not limited to:

10X Genomics Single Cell Multiome Gene Expression and ATAC libraries

Single-cell multi-omics sequencing must include sufficient read depth and coverage. The numbers of reads and sequencing cycles are to be finalized during Phase I to allow for cell type detection. Single-cell multi-omics sequencing data, following cleaning, QC/QA, and library demultiplexing must be securely transmitted to NIH BRAIN Initiative designated partners/data

The contractor shall prepare a technology evaluation proposal and conduct a Phase I task study when promising technologies and library types are identified and requested by the Government, which include but are not limited to sci-ATAC-seq, Hi-C, ChIP-seq, new 10X Genomics protocols (e.g., Chromium X), sci-RNA-seq, scifi-RNA-seq, smart-seq3, and Slide-seq. Phase II task may be adjusted to adopt the new single-cell transcriptomics technologies following the technology validation.

The performance period for General Task Area 4 is anticipated to be six (6) months, with twelve

GENERAL TASK AREA 5: Bulk Tissue Transcriptome and Epigenome Sequencing

The task order has two parts: Phase I (pilot study) to establish quality metrics and common agreement on workflows and data pipelines among the BICAN researchers, NIH BRAIN

Initiative staff and the contractors, and Phase II (production) in which the contractor provides bulk tissue transcriptome and epigenome sequencing of libraries provided by BICAN researchers and deposits the data into designated repositories with automated real-time notification to the Coordinating Unit for Biostatistics, Informatics and Engagement (CUBIE) and

NIH staff. It is expected that initial task order will require Phases I and II, and the option period(s) only request Phase II. The COR will determine which phases are required for the task area.

metrics and uniformity of the BICAN sequencing pipelines across different sites. Contractors must describe how they will participate in BICAN in-person meetings and conference calls as well as the pilot studies to develop standard operating procedures within the network of contractors, investigators and NIH staff. The Sequencing Core contractor will interact with the

BICAN labs and other contractors to generate a report that establishes

(1) a submission and tracking process of the sequencing libraries and the associated metadata,

(2) QC/QA metrics of the sequencing libraries,

(3) QC/QA metrics of sequencing data, including methods for data cleaning and harmonization,

(4) process and timeline of data transfer to the NIH designated partners/data archive(s),

(5) quality performance uniformity across the sequencing facilities,

(6) results of a pilot study and comparison of the sequencing results across all participating contractors

Phase I will be required for the initial task order request; the performance period for Phase I is

Phase II of the task requires obtaining state of the art transcriptome and epigenome sequence profiles from bulk anatomical region- or cell type-enriched samples obtained from BICAN selected studies using short-read and long-read sequencing technologies. Sequencing approaches must include sufficient sequencing depth and read lengths for complete transcriptome and epigenome assembly, as determined in Phase I. For transcriptome sequence profiles, libraries are prepared from multiple brain regions to enable both small and long RNA species detection for transcriptome sequencing. For epigenome sequencing profiles, libraries are prepared from multiple brain regions to enable ensemble analysis of chromatin accessibility, DNA 3D conformation, and DNA methylation and hydroxymethylation. RNA and DNA sequence profile data (raw, processed, and segmented/interpreted), following cleaning, QC/QA, and assembly, must be securely transmitted to NIH BRAIN Initiative designated partners/data

The contractor shall prepare a technology evaluation proposal when promising technologies are identified and requested by the Government. This task may be adjusted to adopt the new technologies following the validation of new transcriptomics and epigenomics technologies.

The performance period for General Task Area 5 is anticipated to be six (6) months, with twelve

[Note 7 to Offerors: Inclusion of either General Task Area 5 or General Task Area 6 is mandatory]

GENERAL TASK AREA 6: Whole Genome and Exome Sequencing

The task order has two parts: Phase I (pilot study) to establish quality metrics and common agreement on workflows and data pipelines among the BICAN researchers, NIH BRAIN

Initiative staff and the contractors, and Phase II (production) in which the contractor provides whole genome and exome sequencing of libraries provided by BICAN researchers and deposits the data into designated repositories with automated real-time notification to the Coordinating

Unit for Biostatistics, Informatics and Engagement (CUBIE) and NIH staff. It is expected that initial task order will require Phases I and II, and the option period(s) only request Phase II. The

COR will determine which phases are required for the task area.

metrics and uniformity of the BICAN sequencing pipelines across different sites. Contractors must describe how they will participate in BICAN in-person meetings and conference calls as well as the pilot studies to develop standard operating procedures within the network of contractors, investigators, and NIH staff. The Sequencing Core contractor will interact with the

BICAN labs and other contractors to generate a report that establishes

(1) a submission and tracking process of the sequencing libraries and the associated metadata,

(2) QC/QA metrics of the sequencing libraries and library pools,

(3) QC/QA metrics of sequencing data, including methods for data cleaning and harmonization,

(4) process and timeline of data transfer to the NIH designated partners/data archive(s),

(5) quality performance uniformity across the sequencing facilities,

(6) results of a pilot study and comparison of the sequencing results across all participating contractors

Phase I will be required for the initial task order request; the performance period for Phase I is

Phase II task requires obtaining Whole Genome Sequencing (WGS) and Whole Exome

Sequencing (WES) using short-read and long-read sequencing technologies from BICAN selected studies. WGS and WES must include sufficient read lengths and coverage to allow for successful rare variant detection, as determined in Phase I. WGS and WES data, following cleaning, QC/QA, and assembly must be securely transmitted to NIH BRAIN Initiative designated partners/data archive(s). The contractor should submit monthly summary reports.

The contractor shall prepare a technology evaluation proposal when promising technologies are identified and requested by the Government. This task may be adjusted to adopt the new technologies following the validation of new technologies.

The performance period for General Task Area 6 is anticipated to be six (6) months, with twelve

GENERAL TASK AREA 7: Novel Omics Sequencing agreement on workflows and data pipelines among the BICAN researchers, NIH BRAIN

Initiative staff and the contractors, and Phase II (production) in which the contractor provides novel omics sequencing of libraries provided by BICAN researchers and deposits the data into designated repositories with automated real-time notification to the Coordinating Unit for

Biostatistics, Informatics and Engagement (CUBIE) and NIH staff. It is expected that initial task order will require Phases I and II, and the option period(s) only request Phase II. The COR will determine which phases are required for the task area.

This task requires obtaining omics sequencing profiles that are novel to the BICAN program.

Measures can include characterization of any transcriptome and epigenome changes in cell type and state whether transitory, permanent, or mutable. Sequencing approaches and library types may include but are not limited to: a) RNA isoform long-read sequencing, b) subcellular compartment RNA sequencing, c) ribosome sequencing, and d) DNA hydroxymethylation sequencing. Novel Omics profile data following cleaning, QC/QA, and assembly must be securely transmitted to NIH BRAIN Initiative designated partners/data archive(s).

When promising technologies and sequencing libraries are identified and requested by the

Government, the contractor shall prepare a technology evaluation proposal and conduct a feasibility study (Phase I). This task requires coordinating and collaborating with other BICAN researchers, contractors, and NIH staff to establish common QC/QA metrics and uniformity of the BICAN sequencing pipelines across different sites. Task order contractors must participate in BICAN in-person meetings and conference calls relevant to this task dealing with quality control, data transfer, and other issues as appropriately outlined by the NIH BICAN network and requested by the Government. The Phase I task order requires a report outlining how the novel omics will benefit the BICAN network and the standard operating procedures for sequencing of samples from the BICAN network. The anticipated performance period for Phase I is 6 months.

If requested, Phase II task requires using novel technology (evaluated in Phase I) to obtain sequencing profiles from BICAN selected studies. The sequencing must include sufficient read lengths and coverage to allow for successful characterization of brain cell diversity, as determined in Phase I. Sequence data, following cleaning, QC/QA, and assembly must be securely transmitted to NIH BRAIN Initiative designated partners/data archive(s). The contractor should submit monthly summary reports.

The performance period for General Task Area 7 is anticipated to be six (6) months, with twelve

[Note 8 to Offerors: For proposal evaluation purposes, the technical evaluation team will evaluate the offeror’s capability to perform the requirements described above for General

Task Areas 1, 2, 3, 4, 5, 6 and 7. 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 contractor's proposal and the contractor's minimum and maximum quantities.

[Note 9 to Offerors: Anticipated Sample Task Orders No. 1 through 7 described are included as separate attachments and identify the current anticipated requirements. The technical evaluation team will also review and evaluate the “Anticipated Sample Task

Orders” and these will potentially be awarded by December 2022. 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.]

[Note 10 to Offerors: Offerors shall provide a brief description of the projects, methods, and any resulting publications.]

[Note 11 to Offerors: Offerors shall provide a brief description of the technology and protocols used for each Task.]

LEVEL OF EFFORT:

General Tasks 1 – 7 will require a team leader with biochemistry/bioinformatics expertise to coordinate the sequencing, analysis and report the results.

GOVERNMENT RESPONSIBILITIES

The Government will coordinate the partnership between the contractors and the BICAN researchers in the delivery of the libraries and associated metadata for sequencing and the sequence datasets to the designated repositories. Biospecimens (including libraries from single cells and bulk tissue) from BICAN grant awarded studies will be provided to the contractors for sequencing. In addition, sample IDs, minimal metadata requirements and QC/QA information such as library quantification may also be provided.

The contractor will receive access to the designated repositories for data submission.

The Government will review and approve the Manual of Operations, bi-weekly status reports, draft final reports and final reports for each Task Order.

DELIVERY OR DELIVERABLES

The turnaround time between the receipt of the sample libraries and deposition of the sequences into the data archive is expected to be 4-10 days, with a maximum time of no more than 14 days. Electronic sequence data will be in the FASTQ format. The contractor is expected to submit associated metadata and sequence data to the NIH-designated data archive(s).

Manuals of Operations, bi-weekly weekly status reports, draft final reports and final reports for each Task Order are expected to be submitted as electronic copies.

REPORTING REQUIREMENTS

All reports required herein shall be submitted in electronic format.

All electronic reports submitted shall be compliant with Section 508 of the Rehabilitation Act of

1973. Additional information about testing documents for Section 508 compliance, including guidance and specific checklists, by application, can be found at:

http://www.hhs.gov/web/508/index.html under "Making Files Accessible."

a. Technical Progress Reports

In addition to the required reports set forth elsewhere in this Schedule, the preparation and submission of regularly recurring Technical Progress Reports will be required in any contract resulting from this solicitation. These reports will require descriptive information about the activities undertaken during the reporting period and will require information about planned activities for future reporting periods. The frequency and specific content of these reports will be determined prior to contract award. [Note: Beginning May 25, 2008, the Contractor shall include the applicable PubMed Central or NIH Manuscript

Submission reference number when citing publications that arise from its NIH funded research.]

TASK AREA 2 - Large-Scale Single-cell Transcriptome Sequencing

For proposal preparation purposes only, it is estimated that only the required electronic version(s) of these reports will be required as follows:

[X] Bi-weekly

[ ] Quarterly

[ ] Semi-Annually

[ ] Annually

[ ] Annually (with a requirement for a Draft Annual Report)

The Contractor shall submit a bi-weekly report describing the activities during the reporting period, and the activities planned for the ensuing reporting period. The initial reporting period consists of the first full two weeks of performance plus any fractional part of the initial week. As a minimum, this report shall include:

i. A qualitative description of overall progress, including the status of the Large-

Scale Single Cell Transcriptome Sequencing, the weekly and monthly Quality

Control (QC) data (used here and throughout encompassing quality assurance and quality control activities), the weekly and monthly production and number of data sequences submitted to the designated data repository, and the quality control metrics established during Phase I of the task order by the contractors, BICAN investigators and NIH BRAIN Initiative staff.

ii. An indication of any current problems that may impede performance, and proposed corrective action iii.A discussion of the work to be performed during the next reporting period; and iv.Recommendations.

For proposal preparation purposes only, it is estimated that electronic version(s) of these reports will be required as follows:

[ ] Final - Upon final completion of the contract

[X] Final - Upon final completion of the contract (with a requirement for a Draft Final

Report)

This report is to include a summation of the work performed and results obtained for the entire contract period of performance. This report shall be in sufficient detail to describe comprehensively the results achieved. The Contractor shall provide the Contracting

Officer with copies of the final report in draft form 30 Calendar days prior to the delivery date for the final version of the final report. The Contracting Officer's Representative

(COR) shall review the draft report and provide the Contracting Officer with comments within 15 Calendar days after receipt. The Contractor, if necessary, shall correct the final report.

TASK AREA 3 - Large-Scale Single-cell Epigenome Sequencing

[X] Bi-weekly

[ ] Quarterly

[ ] Semi-Annually

[ ] Annually

[ ] Annually (with a requirement for a Draft Annual Report)

The Contractor shall submit a bi-weekly report describing the activities during the reporting period, and the activities planned for the ensuing reporting period. The initial reporting period consists of the first two full weeks of performance. As a minimum, this report shall include:

i. A qualitative description of overall progress, including the status of the Large-

Scale Single Cell Epigenome Sequencing, the weekly and monthly Quality

Control (QC) data (used here and throughout encompassing quality assurance and quality control activities), the weekly and monthly production and number of data sequences submitted to the designated data repository, and the quality control metrics established during Phase I of the task order by the contractors, BICAN investigators and NIH BRAIN Initiative staff.

ii. An indication of any current problems that may impede performance, and proposed corrective action

iii. A discussion of the work to be performed during the next reporting period; and

iv. Recommendations.

For proposal preparation purposes only, it is estimated that electronic version(s) of these reports will be required as follows:

Final - Upon final completion of the contract

X Final - Upon final completion of the contract (with a requirement for a Draft Final

Report)

This report is to include a summation of the work performed and results obtained for the entire contract period of performance. This report shall be in sufficient detail to describe comprehensively the results achieved. The Contractor shall provide the Contracting

Officer with copies of the final report in draft form 30 Calendar days prior to the delivery date for the final version of the final report. The COR shall review the draft report and provide the Contracting Officer with comments within 15 Calendar days after receipt.

The Contractor, if necessary, shall correct the final report.

TASK AREA 4 – Large-Scale Single-Cell Multi-omics Sequencing

[X] Bi-weekly

[ ] Quarterly

[ ] Semi-Annually

[ ] Annually

[ ] Annually (with a requirement for a Draft Annual Report)

The Contractor shall submit a bi-weekly report describing the activities during the reporting period, and the activities planned for the ensuing reporting period. The initial reporting period consists of the first two full weeks of performance. As a minimum, this report shall include:

i. A qualitative description of overall progress, including the status of the Large-

Scale Single Cell Epigenome Sequencing, the weekly and monthly Quality

Control (QC) data (used here and throughout encompassing quality assurance and quality control activities), the weekly and monthly production and number of data sequences submitted to the designated data repository, and the quality control metrics established during Phase I of the task order by the contractors, BICAN investigators and NIH BRAIN Initiative staff.

ii. An indication of any current problems that may impede performance, and proposed corrective action

Final - Upon final completion of the contract

X Final - Upon final completion of the contract (with a requirement for a Draft Final

Report)

This report is to include a summation of the work performed and results obtained for the entire contract period of performance. This report shall be in sufficient detail to describe comprehensively the results achieved. The Contractor shall provide the Contracting

Officer with copies of the final report in draft form 30 Calendar days prior to the delivery date for the final version of the final report. The COR shall review the draft report and provide the Contracting Officer with comments within 15 Calendar days after receipt.

TASK AREA 5 - Bulk Tissue Transcriptome and Epigenome Sequencing

[X] Bi-weekly

[ ] Quarterly

[ ] Semi-Annually

[ ] Annually

[ ] Annually (with a requirement for a Draft Annual Report)

The Contractor shall submit a bi-weekly report describing the activities during the reporting period, and the activities planned for the ensuing reporting period. The initial reporting period consists of the first two full weeks of performance. As a minimum, this report shall include:

i. A qualitative description of overall progress, including the status of Bulk Tissue

Transcriptome and Epigenome Sequencing, the weekly and monthly Quality

Control (QC) data (used here and throughout encompassing quality assurance and quality control activities), the weekly and monthly production and number of data sequences submitted to the designated data repository, and the quality control metrics established during Phase I of the task order by the contractors, BICAN investigators and NIH BRAIN Initiative staff.

ii. An indication of any current problems that may impede performance, and proposed corrective action

Final - Upon final completion of the contract

X Final - Upon final completion of the contract (with a requirement for a Draft Final

Report)

This report is to include a summation of the work performed and results obtained for the entire contract period of performance. This report shall be in sufficient detail to describe comprehensively the results achieved. The Contractor shall provide the Contracting

Officer with copies of the final report in draft form 30 Calendar days prior to the delivery date for the final version of the final report. The COR shall review the draft report and provide the Contracting Officer with comments within 15 Calendar days after receipt.

TASK AREA 6 - Whole Genome and Exome Sequencing

[X] Bi-weekly

[ ] Quarterly

[ ] Semi-Annually

[ ] Annually

[ ] Annually (with a requirement for a Draft Annual Report)

The Contractor shall submit a bi-weekly report describing the activities during the reporting period, and the activities planned for the ensuing reporting period. The initial reporting period consists of the first two full weeks of performance. As a minimum, this report shall include:

i. A qualitative description of overall progress, including the status of the Whole

Genome and Exome Sequencing Sequencing, the weekly and monthly Quality

Control (QC) data (used here and throughout encompassing quality assurance and quality control activities), the weekly and monthly production and number of data sequences submitted to the designated data repository, and the quality control metrics established during Phase I of the task order by the contractors, BICAN investigators and NIH BRAIN Initiative staff.

ii. An indication of any current problems that may impede performance, and proposed corrective action

Final - Upon final completion of the contract

X Final - Upon final completion of the contract (with a requirement for a Draft Final

Report)

This report is to include a summation of the work performed and results obtained for the entire contract period of performance. This report shall be in sufficient detail to describe comprehensively the results achieved. The Contractor shall provide the Contracting

Officer with copies of the final report in draft form 30 Calendar days prior to the delivery date for the final version of the final report. The COR shall review the draft report and provide the Contracting Officer with comments within 15 Calendar days after receipt.

TASK AREA 7 - Novel Omics Sequencing

[X] Bi-weekly

[ ] Quarterly

[ ] Semi-Annually

[ ] Annually

[ ] Annually (with a requirement for a Draft Annual Report)

The Contractor shall submit a bi-weekly report describing the activities during the reporting period, and the activities planned for the ensuing reporting period. The initial reporting period consists of the first two full weeks of performance. As a minimum, this report shall include:

i. A qualitative description of overall progress, including the status of the Novel

Omics Sequencing, the weekly and monthly Quality Control (QC) data (used here and throughout encompassing quality assurance and quality control activities), the weekly and monthly production and number of data sequences submitted to the designated data repository, and the quality control metrics established during

Phase I of the task order by the contractors, BICAN investigators and NIH BRAIN

Initiative staff.

ii. An indication of any current problems that may impede performance, and proposed corrective action

Final - Upon final completion of the contract

X Final - Upon final completion of the contract (with a requirement for a Draft Final

Report)

This report is to include a summation of the work performed and results obtained for the entire contract period of performance. This report shall be in sufficient detail to describe comprehensively the results achieved. The Contractor shall provide the Contracting

Officer with copies of the final report in draft form 30 Calendar days prior to the delivery date for the final version of the final report. The COR shall review the draft report and provide the Contracting Officer with comments within 15 Calendar days after receipt.

b. Other Technical Reports

1. TASK AREA 1 - Manual of Operations

a. BICAN Final Manual of Operations for Task Areas 2 - 7 (Large-Scale Single-cell

Transcriptome Sequencing, Large-Scale Single-cell Epigenome Sequencing, Large-

Scale Single-Cell Multi-omics Sequencing, Bulk Tissue Transcriptome and

Epigenome Sequencing, Whole Genome and Exome Sequencing, and Novel Omics

Sequencing, as proposed)

Within one (1) month of contract award, the Contractor shall deliver a final copy of the

Manual of Operations included in their proposal. The final Manual of Operations will incorporate all changes or modifications agreed upon by the Government and the Contractor during contract negotiations and the first month of contract performance. At a minimum, the final Manual of Operations shall contain the following:

i. Detailed description of sample receipt, storage, and tracking methodology assuring participant confidentiality, including:

1. Procedures for the receipt of samples and metadata, including shipping and packaging of samples and acquisition of metadata and integration into the lab information management system (LIMS), (The contractor is expected to provide packaging materials and coordinate shipping of samples from the BICAN investigators).

2. Required procedures for omics library sample preparation, aliquotting, labeling, and shipping, and minimum acceptable standards for sample quantity and quality for samples submitted for proposed omics.

3. Procedures for tracking data and sample identification information for samples submitted for proposed omics sequencing.

4. Methods for electronic and genetic tracking of library samples including but not limited tosample and sequencing barcodes and gender identification; minimization of sample switches, losses, and cross contamination; tracking of work, and details of the in-house LIMS.

5. Methods for storage of omics library samples and back-up plans.

6. Recommendations for sample preparation and other strategies to assist in minimizing batch effects and other biases.

7. Updates in the above agreed to between the Government, BICAN investigators and the Contractor.

[Note 12 to Offerors: The Offeror will provide (1) packaging materials and identification information (i.e. barcode labels) for the sample libraries and (2) shipping of the samples from the BICAN investigators to the Offeror. The samples are not expected to be returned to the BICAN investigators.]

ii. Detailed description of the proposed omics profiling method, including:

1. Methods for optimizing and evaluating the proposed omics sequencing method and platform.

2. Instrumentation and robotics necessary to perform the proposed omics sequencing and procedures for equipment calibration and maintenance.

3. Methods for incorporating technology development to increase efficiency, quality and throughput.

4. Laboratory information management systems to be used, including software, nonproprietary platform, hardware, query system, transmission requirements, backups, and security.

5. A detailed workflow of the proposed omics analysis and Quality Control (QC)

(which may include) quantification, library pool prep, on-instrument sequencing raw data and demultiplexing, preprocessing, mapping, post-alignment processing, variant calling, annotation, and prioritization, including criteria, the tools used and versioning.

iii. Detailed description of laboratory QC procedures, including:

1. Methods to reduce or eliminate systematic errors.

2. Source and frequency of use of internal standards, repeat samples, and blank samples.

3. Procedures for computational checking and rechecking, assessment of reading errors and data consistency, and calculation of error rate and failure rate of sequencing attempts and for samples.

4. Methods for routine alternate procedures to be used when proposed omics sequencing fails.

5. Methods to reduce or eliminate errors in computational and informatics aspects of the sequencing.

6. Methods for identifying sample mix-ups.

7. Procedures for identifying and implementing corrective actions based on QC.

iv. Detailed description of genetic analysis and bioinformatics for data cleaning including:

1. Procedures for analysis including but not limited to the checks for internal standards and QC/Quality Assurance (QA) used in the workflow of the proposed omics analysis: raw data QC, preprocessing, mapping.

2. Methods for correcting inconsistencies and handling inconsistent data to maximize accuracy.

v. Detailed description of informatics used for sequencing, database management, and data transfer including:

1. Software and hardware system components, including commercial products and custom software developed for support of database, associated informatics functions, and protocols and formats for data transfer, including a description of the rationale for the chosen database information model and past experience with it.

Offerors should catalog proprietary and open-source elements, and identify specific license limitations including terms that could potentially affect future resource access and portability. For customized applications, describe the use of industry and informatics best practices in the development of the components. Data information management systems to be used, including software, nonproprietary platform(s), hardware, backups, and security.

vi. Key personnel including their responsibilities and contact information, and a key personnel replacement plan

2. TASK AREAS 2 – 7

a. Phase I (Pilot) Report

Secure delivery of pilot QC of representative cohort(s) omics samples to COR, BICAN investigators, designated contractors, NIH staff, and BRAIN Initiative designated data archive or data coordinating center.

b. Timeline

Provide timeline for novel omics profiles at 1, 3, and 6 months to Contracting officer, COR, and designated NIH staff.

c. Technology Evaluation Proposals

When promising technologies are identified and when requested by COR, the contractor shall prepare a technology evaluation proposal. The proposal shall include an assessment of the potential scientific impact and the costs associated with adopting the new technology.

In addition, the Government may require reports focusing on specific technologies and applications. Follow-up reports may also be required.

c. Other Reports/Deliverables

1. Information Security and Physical Access Reporting Requirements

The Contractor shall submit the following reports as required by the INFORMATION

AND PHYSICAL ACCESS SECURITY Article in SECTION H of this contract. Note: Each report listed below includes a reference to the appropriate subparagraph of this article.

a. Roster of Employees Requiring Suitability Investigations

The Contractor shall submit a roster, by name, position, e-mail address, phone number and responsibility, of all staff (including subcontractor staff) working under the contract who will develop, have the ability to access, or host and/or maintain a

Federal information system(s). The roster shall be submitted to the Contracting

Officer's Representative (COR), with a copy to the Contracting Officer, within 14 calendar days of the effective date of the contract.

b. IT Security Plan (IT-SP)

The contractor shall submit the IT-SP within thirty (30) days after contract award.

The IT-SP shall be consistent with, and further detail the approach to, IT security contained in the Contractor's bid or proposal that resulted in the award of this contract. The IT-SP shall describe the processes and procedures that the

Contractor will follow to ensure appropriate security of IT resources that are developed, processed, or used under this contract.