Request for Information (RFI) Regarding Potential Uses of Stored Biospecimens from the Common Fund GTEx Project

Notice Number: NOT-RM-12-028

Key Dates
Release Date: September 14, 2012
Response Date: October 5, 2012

Issued by
National Institutes of Health (NIH)

Purpose

This Request for Information (RFI) is intended to gauge interest in using stored biospecimens collected in the Genotype-Tissue Expression (GTEx) Project of the NIH Common Fund.  The NIH is considering a Funding Opportunity Announcement (FOA) with set-aside funds to support future studies utilizing these biospecimens.  Information obtained via this RFI will help the GTEx Working Group (WG) understand the potential demand for GTEx biospecimens, plan scientific reviews, and assess the need for other access mechanisms beyond an FOA.

The NIH is interested in making maximal use of this unique biospecimen resource, rich with clinical and genomic information.  Except for the fibroblast and lymphoblastoid cell lines, biospecimens are of limited quantity and are non-renewable.  Potential uses that are comprehensive (genomic vs single gene or small gene networks, proteomic vs single proteins or small networks of proteins, etc.) and complementary to existing gene expression and variation data, are preferred.  Scientific questions that are equally well addressed using other sample sets will probably not be suitable, while those that take full advantage of the unique aspects of GTEx, such as the multiple tissues from each donor and the gene expression information, are particularly sought. In addition to scientific review, all proposals to use GTEx samples would also go through a Biospecimen Access Committee (currently being formed).  GTEx data will be made available through dbGaP (http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000424), and eventually through other data portals, and is not the subject of this RFI.

Background

The primary goal of GTEx is to establish a resource database and associated tissue bank in which to study the relationship between genetic variation and gene expression and other molecular phenotypes in multiple reference tissues. An initial pilot phase resulted in biospecimen collection from over 175 post-mortem donors by the summer of 2012. Having met milestones, the project is scaling up to include approximately 900 post-mortem donors by the end of 2015. The GTEx project obtained authorization for broad future research use from the deceased donor’s next of kin.
 
The collection involves more than 30 tissues from each post-mortem donor (see Table 1). When consented, the cerebral cortex and cerebellum are sampled immediately, and the remaining whole brain is shipped to a brain bank, where 9 additional regions are sampled.  Post-mortem donors of any racial and ethnic group and sex who are age 21-70 in whom biospecimen collection can start within 24 hours of death are eligible.  Donors are expected to have a typical prevalence of chronic diseases because there are only a few exclusionary criteria, such as human immunodeficiency virus (HIV), viral hepatitis, and metastatic cancer. All donors are characterized for germline genetic variation through dense genotyping of a blood sample.  All tissues of sufficient quality undergo gene expression analysis using deep RNA sequencing.  This RFI deals with potential uses of biospecimens beyond the genotyping and gene expression analyses described above.  More information about GTEx can be found at http://commonfund.nih.gov/GTEx/.

Biospecimen acquisition for GTEx is organized under the National Cancer Institute’s (NCI) cancer Human Biobank (caHUB) initiative (http://caHUB.cancer.gov), part of the Office of Biorepositories and Biospecimen Research (OBBR), together with SAIC-Frederick, Inc. (SAIC-F), the prime contractor to the NCI.  Biospecimen collection is accomplished through Biospecimen Source Sites (BSS) and a Comprehensive Biospecimen Resource (CBR).  Aliquots of tissue from each donor are processed by the GTEx Laboratory, Data Analysis and Coordinating Center (LDACC).

We expect to be able to make available to the scientific community the following sample types:

In addition to biospecimens, the following data will be available (potential uses of the data are not the subject of this RFI):

Openly available (data portal under development):

Available only through controlled access (dbGaP):

See table 1 for a summary of sample and tissue types collected in GTEx.  Collection and analyses are ongoing and therefore results will change over time.  A searchable database of available samples is under development.

Table 1: Summary of approximate numbers of tissues collected and amount of sample remaining based on the first 150 donors.

 

Preserved Tissue (PAXgene - not paraffin embedded, unless otherwise specified)

Stored RNA

Stored DNA

Tissue Type

N          (N with RIN>6)

Median Weight (mg)

Median Total Amt (ug)

Median Conc. (ng/uL)

Median Total Amt (ug)

Median Conc. (ng/uL)

Adipose, Subcutaneous

144 (108)

360

1.8

29.1

0.8

7.6

Adipose, Visceral (Omentum)

17 (10)

299

2.4

36.3

0.9

9.7

Adrenal Gland

107 (62)

315

13.5

314.9

6.0

55.6

Artery, Aorta (Ascending or Thoracic)

133 (83)

254

2.2

64.3

1.1

10.2

Artery, Coronary

97 (65)

110

2.9

87.5

1.8

17.4

Artery, Tibial

142 (115)

95

1.7

62.6

1.7

18.1

Bladder, Urinary*^

121 (75)

420

4.8

144.8

2.9

30.2

Brain, Cerebellum

36 (24)

209

8.1

262.6

20.9

145.8

Brain, Cortex

35 (22)

203

5.4

192.4

1.8

15.8

Brain, Amygdala@

34 (21)

130

5.3

188.4

1.0

19.4

Brain, Anterior cingulate cortex (BA24)@

35 (16)

144

6.9

212.8

1.0

18.0

Brain, Caudate (basal ganglia)@

35 (28)

136

5.9

195.6

0.9

15.6

Brain, Cerebellar Hemisphere@

35 (21)

200

8.1

266.1

7.8

136.1

Brain, Frontal Cortex (BA9)@

35 (22)

210

5.9

188.5

1.0

19.9

Brain, Hippocampus@

34 (24)

164

5.4

202.0

0.9

20

Brain, Hypothalamus@

34 (19)

123

4.3

165.8

1.0

23.7

Brain, Nucleus accumbens (basal ganglia)@

35 (28)

115

5.6

200.2

0.9

16.3

Brain, Putamen (basal ganglia)@

33 (18)

118

5.7

196.0

1.2

21.7

Brain, Spinal cord (cervical c-1)@

24 (17)

136

2.6

86.6

0.6

13.4

Brain, Substantia nigra@

33 (20)

120

4.8

146.1

0.6

14.5

Breast, Mammary Tissue

87 (56)

375

2.2

32.1

1.1

11.6

Cervix, Ectocervix*

32 (24)

303

3.6

111.7

3.6

33.2

Cervix, Endocervix*

34 (22)

311

5.0

150.8

6.3

47.6

Colon, Transverse

144 (84)

288

8.2

235.3

6.2

58.6

Colon, Sigmoid

15 (9)

317

6.9

200.1

5.1

53.3

Esophagus, Gastroesophageal Junction

16 (10)

489

3.7

106.3

3.6

38.1

Esophagus, Mucosa

139 (111)

159

14.4

332.7

5.5

49.2

Esophagus, Muscularis

140 (100)

345

5.5

166.4

2.9

28.3

Fallopian Tube*

32 (26)

183

7.5

239.6

6.9

62.8

Heart, Atrial Appendage

12 (11)

329

4.0

132.8

2.0

21.5

Heart, Left Ventricle

116 (79)

312

4.4

185.5

1.6

14.8

Kidney, Cortex

73 (10)

318

8.9

265.5

9.6

80.0

Kidney, Medulla*

41 (10)

322

8.2

240.1

9.0

84.9

Liver

81 (43)

367

23.8

361.3

4.8

48.0

Lung

129 (108)

303

4.9

204.2

5.6

54.4

Muscle, Skeletal

146 (133)

350

2.9

114.1

1.4

12.0

Nerve, Tibial

139 (97)

212

1.2

48.0

2.1

19.8

Ovary

45 (35)

400

10.4

283.9

14.6

124.9

Pancreas^

130 (67)

375

50.7

363.6

10.1

93.5

Pituitary Gland

33 (16)

119

17.7

335.5

14.1

153.5

Prostate

83 (39)

345

7.9

236.2

6.0

60.5

Skin, Sun exposed (Lower Leg)

147 (94)

300

2.6

98.2

2.6

24.4

Skin, Not sun exposed (Suprapubic)

17 (11)

359

3.4

118.8

3.3

35.4

Spleen^

137 (33)

417

15.4

346.8

13.9

133.2

Stomach^

144 (82)

338

12.3

299.6

6.7

57.7

Terminal Ileum (Peyer’s patch)

15 (9)

288

7.5

229.2

9.8

104.8

Testis

92 (64)

339

13.5

328.1

7.4

62.2

Thyroid

126 (94)

341

4.9

213.9

8.2

81.6

Uterus

41 (31)

364

7.9

226.8

9.8

73.9

Vagina

48 (34)

387

4.8

141.2

4.5

43.1

Whole Blood&

149 (144)

-

6.6

102.8

19.4

115.1

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 



















* Tissues collected only during the pilot phase (i.e., the final numbers will not be significantly higher); @ Fresh Frozen Tissue; ^ 15-30% of samples show severe autolysis; & Blood for RNA collected in PAXgene Blood RNA tubes, Blood for DNA collected in acid citrate dextrose (ACD) tubes. Protocols for collecting minor salivary glands are under review.

Information Requested

The NIH Common Fund GTEx Working Group is interested in knowing the level of interest in using GTEx biospecimens, the types of analyses being considered, the level of funding support that would be required, and how well suited the existing sample types are for the proposed analyses.

Please provide the following types of information for assays or ideas that could be accomplished with GTEx biospecimens.

Responses

To assure consideration, your responses must be sent to nhgrigtexrfi@mail.nih.gov and received by midnight on October 5, 2012.  

Responses to this RFI are voluntary. The comments collected will be analyzed and considered in planning and development of future initiatives.  We do not intend to publish a summary of responses received or any other information provided, except very broad characterizations, such as the number of responses received and the relative demand of various tissue types.  Despite this, proprietary, classified or confidential information should not be included in your response.  This RFI is for planning purposes only and is not a solicitation for applications or an obligation on the part of the United States (U.S.) Government to provide support for any ideas identified in response to it.  Please note that the U.S. Government will not pay for the preparation of any comment submitted or for its use of that comment.

Inquiries

For further information contact:
 
Simona Volpi, Ph.D.
Email: nhgrigtexrfi@mail.nih.gov


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