Investigation Title Hodgkin_IV-IIIB_Ben-Dov_CRG Comment[AdditionalFile:XLSX] Ben-Dov_C_HD.xlsx Comment[Submitted Name] Hodgkin_IV-IIIB_Ben-Dov_CRG Experimental Design cell_type_comparison_design co-expression_design all_pairs transcription profiling by array Experimental Design Term Source REF The MGED Ontology The MGED Ontology EFO Comment[AEMIAMESCORE] 5 Comment[SecondaryAccession] Comment[ArrayExpressReleaseDate] 2010-12-31 Comment[ArrayExpressAccession] E-MEXP-2959 Comment[MAGETAB TimeStamp_Version] 2010-10-29 15:55:29 Last Changed Rev: 14857 Experimental Factor Name CELL_TYPE Experimental Factor Type cell_type Experimental Factor Term Source REF Person Last Name Ben-Dov Person First Name Claudia Person Mid Initials P Person Email claudia.bendov@crg.es Person Phone +34 933160100 Person Fax Person Address Gene Regulation, Dr. Aiguader 88, Barcelona, Barcelona, 08003, Spain Person Affiliation Center for Genomic Regulation Person Roles submitter Person Roles Term Source REF The MGED Ontology Quality Control Type biological_replicate dye_swap_quality_control Quality Control Term Source REF The MGED Ontology The MGED Ontology Replicate Type Replicate Term Source REF Normalization Type Normalization Term Source REF Date of Experiment Public Release Date 2010-12-31 PubMed ID Publication DOI Publication Author List Publication Title Publication Status Publication Status Term Source REF Experiment Description Hodgkin lymphoma derived cell lines (from the Deutsche Sammlung von Mikroorganismen und Zellkulturen) were cultured in RPMI 1640 medium supplemented with

20% (HDML-2) or 10% (HD-MY-Z) heat inactivated fetal calf serum. Cytoplasmic RNA was extracted according to "Cytoplasmic_RNA_CRG" protocol available at Arrayexpress Protocol Name P-MTAB-17626 P-MTAB-17627 P-MTAB-17629 P-MTAB-17628 Protocol Type nucleic_acid_extraction labeling hybridization bioassay_data_transformation Protocol Description 1) Cytoplasmic RNA, including on column DNAse treatment, was extracted from Hodgkin cell lines with RNeasy® Mini Kit from QIAGEN according to manufacturer's instructions.

http://www.qiagen.com/selectlocation.aspx?redirect=%2fliterature%2frender.aspx%3fid%3d576.

2) Samples were quantified by NanoDrop and subject to quality control with Bioanalyzer (Agilent).






(Parameters: Extracted product = OTHER: cytoplasmic RNA, Amplification = none) Agilent Low RNA Input Fluorescent Linear Amplification Kit (5184-3526)

NOTE: in some steps there are two different amounts X/Y. "X" is according to the original protocol."Y" is according to a modified protocol (Syed HA, Threadgill DW. Enhanced oligonucleotide microarray labeling and hybridization. Biotechniques. 2006 Dec;41(6):685-6).

A) cDNA Synthesis



0. Pre warm the 5X first strand buffer 3-4’ at 65°C, vortex, spin and keep it at RT

1. Add to a 1.5 ml Eppendorf tube 500 ng total RNA in 9.3/ 5.8 ?l H2O (Ambion)

2. Add 1.2/ 0.8 ?l of Oligo dT-T7 promoter primer (Agilent Kit) + 1/ 0.67 ?l random Nanomer-T7 (CGTAATACGACTCACTATAGGGNNNNNNNNN; HPLC purified)

3. Incubate at 65°C for 10’ (block)

4. Ice 5’

5. Prepare the following Master mix

1X 1X

5X Buffer 4 ?l / 2 ?l

0.1M DTT 2 ?l / 1 ?l

10mM dNTPmix 1 ?l / 0.5 ?l

MMLV RT 1 ?l / 0.6 ?l

RNAse out 0.5 ?l/ 0.3 ?l

TOTAL 8.5 ?l/ 4.4 ?l



6. Add 8.5/4.4 ?l master mix to the tube (step 4).

7. Incubate at 40°C 2 hs (in water bath), cover the tubes with parafilm.

8. Incubate 65°C 15’ (block).

9. Ice 5’ and spin.



B. cRNA SYNTHESIS



NOTE: From now avoid exposure to light

1. Add 2.4/ 0.5 ?l Cy3 or Cy5-CTP 1mM to the former tube

2. Prepare the following Master mix

Pre warm the 50% PEG 1’ at 40°C in water bath, vortex and spin keep at RT



1X 1X

H2O 15.3 ?l /3.83 ?l

4X Transcription buffer 20 ?l /5 ?l

0.1M DTT 6 ?l /1.5 ?l

NTPmix 8 ?l /2 ?l

50% PEG 6.4 ?l /1.6 ?l

RNAse out 0.5 ?l /0.12 ?l

Inorganic pyrophosphatase0.6 ?l /0.15 ?l

T7 RNA polymerase 0.8 ?l /0.3 ?l

TOTAL 57.6 ?l /14.50 ?l



3. Add 57.6/14.5 ?l mix to the tube, soft vortex and spin.

4. Incubate at 40°C 2 hs in water bath. Cover the tubes with parafilm.

5. Cover the water bath to avoid light exposure



C. cRNA PURIFICATION (Qiagen RNAeasy mini kit)



1. Add 20/ 80 ?l H2O to former tube (to reach 100 ?l)

2. Add 350 ?l buffer RLT, short vortex

3. Add 250 ?l 100% Ethanol, mix well by pipetting.

4. Transfer sample to column, spin 30’’, 13000 rpm, 4°C

5. Transfer column to new tube and add 500 ?l buffer RPE, spin 30’’ 13000 rpm, 4°C

6. Repeat, add 500 ?l buffer RPE, spin 3’, 13000 rpm, 4°C

7. Add 30 ?l H20, wait 1’, spin 30’’, 13000 rpm, 4°C

8. Repeat, Add 30 ?l H20, wait 1’, spin 30’’, 13000 rpm, 4°C

9. Aliquot 3?l for Bioanalyzer and NanoDrop

10. Store rest of sample at -80°C



Expected yield: 400ng/??l; 30-40 pmol dye/ ?g.

120-170ng/??l; 30-40 pmol dye/ ?g


(Parameters: Mass unit = Micro gram, Amplification = none) FRAGMENTATION AND HYBRIDIZATION.

Agilent In situ hybridization kit plus (5184-3568)



1. Prepare 5.5-6.75 ug of each labeled-cRNA in the same tube. Equal amount of both samples, and similar pmol dye/ug of cRNA according to the NanoDrop. (Up to 3-4 units of difference)

2. Add 50 ul of labeled controls from Agilent.

3. Add 10 ul of 25X fragmentation buffer.

4. Add H2O up to 250 ul.

5. Incubate 30’ at 60ºC. Cover the tubes with parafilm.

6. Cover the water bath with aluminum to avoid light exposure.

7. Remove the tube and add 250 ul of hybridization buffer. Mix by pippetting avoiding bubbles formation.

8. Set up the hybridization chamber (Agilent, Cat.#: G2534A) and add the solution on top of the glass slide.

9. Hybridize 60ºC 18hs. at 6 RPM.



WASHING OF THE ARRAY

- 20x SSC is commercial from AMRESCO

- Triton is coming with Agilent hybridization kit



Wash solution 1.

MiliQ water (steril) 350 ml

20X SSC 150 ml

10% Triton X-102 250 ?l

TOTAL 500 ml

Wash solution 2.

MiliQ water (steril) 498 ml

20X SSC 2.5 ml

10% Triton X-102 250 ?l

TOTAL 500 ml

FILTER both solutions with “Stericup” from Milipore. Keep solution 1 at RT, and 2 at 4ºC.



- Both solutions should be fresh

- It is critical to perform the whole process in an atmosphere free of ozone and light.



1. Remove the array from the chamber inside a can with wash solution 1, try to avoid contact with air.

2. Quickly, put the array inside another box (black) containing wash solution 1, and cover the box. Shake it for 10’ at RT at 150 RPM.

3. Pass the slide to a new box containing cold wash solution 2. Shake it inside an ice box for 5’ at 150 RPM.

4. Dry the slide with Nitrogen pistol.

5. Assembly the scanner chamber.


(Parameters: Chamber type = OTHER: Agilent, Cat.#: G2534A, Quantity of label target used = 6, Mass unit = Micro gram, time = 18, Tiny time unit = hours, Volume unit = Micro litre, temperature = 60) The background correction method used in the analysis was Normexp (Ritchie, et al., 2007). Locally weighted linear regression (LOWESS) analysis was used as a normalization method (Smyth G.K.et al., 2003)



-Smyth, G. K., and Speed, T. P. (2003). Normalization of cDNA microarray data. Methods 31, 265-273.

-Ritchie, ME, Silver, J, Oshlack, A, Holmes, M, Diyagama, D, Holloway, A, and Smyth, GK (2007). A comparison of background correction methods for two-colour microarrays. Bioinformatics 23, 2700-2707 Protocol Parameters Protocol Hardware Protocol Software Protocol Contact Protocol Term Source REF The MGED Ontology The MGED Ontology The MGED Ontology The MGED Ontology SDRF File E-MEXP-2959.sdrf.txt Term Source Name The MGED Ontology EFO ArrayExpress The MGED Ontology EFO Term Source File http://mged.sourceforge.net/ontologies/MGEDontology.php http://www.ebi.ac.uk/efo/ http://www.ebi.ac.uk/arrayexpress http://mged.sourceforge.net/ontologies/MGEDontology.php http://www.ebi.ac.uk/efo/ Term Source Version