epigenetics 2013

Sample & Assay Technologies- 1 -Profiling genes by pathways and diseases

Understanding Gene Expression and Epigenetics Using a Pathway Approach:

PCR Array Systems for Gene & MicroRNA Expression Profiling

CpG Island Methylation Analysis and ChiP

Samuel J. Rulli Jr., Ph.D.qPCR Applications [email protected]

The PCR Arrays are intended for molecular biology applications. This product is not Intended for the diagnosis, prevention, or treatment of disease.


Understanding Gene Expression and Epigenetics Using a Pathway Approach:

Questions, Comments, Concerns?US Applications Support

[email protected]

PCR Array Systems for Gene & MicroRNA Expression Profiling

CpG Island Methylation Analysis and ChiP


Questions, Comments, Concerns?Global Applications Support

[email protected]


Seminar Overview

�What is Epigenetics?

�PCR Arrays for Gene Expression� Profiling Tumor and Metastatic Tumor Cells

�PCR Arrays for Epigenetic Applications� Profiling miRNA Biomarkers in Colon Cancer� Profiling DNA Methylation in Breast Cancer Cell

lines and Normal Breast Tissue� Profiling Chromatin Structure through Histone

Modifications

�Summary and Questions

Cancer Research

Apoptosis

Cell Cycle

Inflammation

ECM/Adhesion

Neuroscience

Signal Transduction

Stem Cell/Development

Toxicology/ Drug ADME



Seminar Overview




lines and Normal Breast Tissue � Profiling Chromatin Structure through Histone

Modifications


The applications presented here are for research purposes. Not for diagnostic use.

Cancer Research

Apoptosis

Cell Cycle

Inflammation

ECM/Adhesion

Neuroscience

Signal Transduction




What is Epigenetics?

�Epigenetics: �“Epi” from Greek meaning “above or over genetics”

�Biological Definition: �Something that effects the Phenotype without changing the Genotype;

�Something that can effect gene expression without causing a mutation in the DNA code


Structural Gene “A”

mRNA ”A”

Gene Expression is Complex with multiple layers of control

TSS (+1)

Transcription Initiation Complex

+

–

Activated Transcription Factors

p53

NFκB

p53 BS NFκB BS

Histones

MeMeMe

Histones

ACAC Me MeMe Me Me Me

RNAi:miRNA

Current View of Gene Expression

Protein “A”



mRNA ”A”

TSS (+1)



p53

NFκB

p53 BS NFκB BS

Histones

MeMeMe

Histones


RNAi:miRNA

Multiple Epigenetic mechanisms influence Gene Expression




mRNA ”A”

TSS (+1)



p53

NFκB

p53 BS NFκB BS

Histones

MeMeMe

Histones


RNAi:miRNA

PCR Arrays for Gene Expression and Epigenetic Regulation


Protein “A”


Epigenetics effects multiple pathways and diseases

�Biological Mechanisms of Epigenetics:

�miRNA �Regulates translation or stability of mRNA

�DNA Methylation: �Regulates transcription factor access, chromatin structure

�Histone modifications: �Regulates bulk chromatin structure and transcription factor access

�Biological Pathways and Diseases Effected by Epigenetics:�Cancer- methylation of tumor suppressor genes�Differentiation- changes in the histone code�Immunology: miRNA regulation of cell cycle proteins by viruses

�Almost all pathways and diseases may have an underlying Epigenetic component

HOW CAN RESEARCHERS PROFILE GENE EXPRESSION AND EPIGENETIC MECHANISMS?


ANSWER: PCR Arrays

�WHAT IS A PCR ARRAY?

�Collection of SYBR-Green based qPCR Assays with biological content with�Focus on a Disease or Pathway

�Available for any qPCR instrument

�Available for a variety of laboratory applications:�mRNA profiling (Gene Expression)�miRNA profiling�DNA Methylation�Chromatin Precipitation

�Part of a complete “System”�Sample Isolation to Final Data Publishable Data Component


5 Components in the PCR Array System

PCR ARRAYS are a Complete System for Pathway-Focused Gene Expression Analysis

1. Sample Isolation (QIAGEN RNeasy) *

2. RT2 PCR Arrays (96, 384 and Rotorgene Q formats)

3. RT2 First Strand kit **

4. RT2 SYBR Green Master Mix

5. Free data analysis software (web or excel-based)

� Publishable story� Ease of use� Relevant genes� Accurate � Reliable

Complete System from Sample Preparation to Fold Cha nge Results

*substitute QIAGEN miRNeasy ** substitute miScriptII RT Kit for miRNA*substitute QIAGEN DNeasy Blood and Tissue; **substitute EpiTect Methyl II RE Kit


Seminar Overview





Modifications



Cancer Research

Apoptosis

Cell Cycle

Inflammation

ECM/Adhesion

Neuroscience

Signal Transduction




PCR Arrays for Gene Expression

Cancer Research

What are the gene expression differences between a metastatic and non-metastatic Breast Tumor?

Research Question:


Anatomy of a RT 2 Profiler PCR Array (for mRNA Profiling)

.84 Pathway-Specific Genes of Interest

.5 Housekeeping Genes

.Genomic DNA Contamination Control

.Reverse Transcription Controls (RTC)

.Positive PCR Controls (PPC)


.84 Pathway-Specific Genes of Interest

.5 Housekeeping Genes

.Genomic DNA Contamination Control

.Reverse Transcription Controls (RTC)

.Positive PCR Controls

.(PPC)

Anatomy of a RT 2 Profiler PCR Array (for mRNA Profiling)


�5 Housekeeping Genes Controls� Flexibility - researchers select the most stable reference (“housekeeping”) gene for their

experimental situation� Human: GAPDH, ACTB, B2M (Beta-2-Microglobulin), HPRT1 (Hypoxanthine

Phosphoribosyltransferase 1), RPL13A (Ribosomal Protein 13A)

�Sample and qPCR Performance Controls� Reverse Transcription Controls (RTC)

� Control for impurities that may degrade RNA or inhibit RT enzyme� Positive PCR Controls (PPC)

� Control for inhibitors of the PCR step� Used in conjunction with RTC assay to establish RT efficiency

� Genomic DNA Contamination Control (GDC) � Detect gDNA contamination

– Single exon genes important for biology (can’t design cross-intron qPCR Assays)

– Pseudo-genes confound analysis of low expressing genes (detected with cross-intron assays)

– Incorporated DNA removal step in cDNA synthesis kit to remove residual genomic DNA

Built-in Standard and Performance Controls


. cDNA Synthesis (C-03 kit)– Genomic DNA Removal Step (5 min.)– Reverse Transcription Step (20 min.)

. Load Plates � 1 Sample per PCR Array� 2 minutes with multi-channel pipet

. Run 40 cycle qPCR Program � Standard cycling conditions for all

Real Time PCR Instruments� 2 hours

. Upload and Analyze Data� 15 minutes from Raw Ct to Fold Change Data

How RT2 Profiler PCR Arrays Work


Data Analysis

.Web-Based Software� No installation or licensing needed

.From Raw Ct Values to Fold Change Results� ∆∆C(t) Method

.Multiple Analysis Formats� Scatter Plot� Volcano Plot� Multi-Group Plot� Clustergram

Also available as downloadable Excel templates

Scatter Plot

Volcano Plot

Clustergram


Wet Bench QC Validation of ALL qPCR Assays on every PCR Array

All PCR Arrays are Wet-Bench Validated

qPCR Assays on each PCR Array are tested for

� Sensitivity: constant C(t) value for same amount of template

� Amplification Efficiency:single curve analysis and standard curve dilutions

� Specificity:single: single melt-peak during dissociation

Validation performed on each lot (synthesized oligon ucleotides) of Primers


PCR Arrays for All Biomedical Researchers

Complete PCR Array List

384-Well Custom ArraysDiabetesp53 Signaling

96-Well Custom ArraysAtherosclerosiscAMP / Calcium Signaling

Custom PCR ArraysOther DiseasesMAP Kinase Signaling

Stress & ToxicityInsulin Signaling

Neurogenesis and Neural Stem CellOxidative StressDNA Damage Signaling

Neurotrophins & ReceptorsDrug TransportersJak / Stat Signaling

Neurotransmitter ReceptorsDrug Phase I EnzymesNFkB Signaling

Neuroscience Ion ChannelsDrug MetabolismSignal Transduction PathwayFinder

NeuroscienceToxicology & Drug MetabolismSignal Transduction

ECM & AdhesionToll-like ReceptorsCancer Drug Resistance

Growth FactorsTNF LigandsAngiogenesis

OsteogenesisTh1-Th2-Th3Cancer PathwayFinder

Endothelial Cell BiologyNF-κB Signaling PathwayTumor Metastasis

TGFβ / BMP SignalingChemokines Breast Cancer & Estrogen Receptor

Notch SignalingCommon CytokinesHuman miRNA Array (NEW!)

Wnt SignalingTh17 for Inflammation (NEW!)Cell Cycle

Stem CellsInflammatory CytokinesApoptosis

Development & Stem CellsCytokines & InflammationCancer and Apoptosis

Complete PCR Array List

384-Well Custom ArraysDiabetesp53 Signaling

96-Well Custom ArraysAtherosclerosiscAMP / Calcium Signaling

Custom PCR ArraysOther DiseasesMAP Kinase Signaling

Stress & ToxicityInsulin Signaling

Neurogenesis and Neural Stem CellOxidative StressDNA Damage Signaling

Neurotrophins & ReceptorsDrug TransportersJak / Stat Signaling

Neurotransmitter ReceptorsDrug Phase I EnzymesNFkB Signaling

Neuroscience Ion ChannelsDrug MetabolismSignal Transduction PathwayFinder

NeuroscienceToxicology & Drug MetabolismSignal Transduction

ECM & AdhesionToll-like ReceptorsCancer Drug Resistance

Growth FactorsTNF LigandsAngiogenesis

OsteogenesisTh1-Th2-Th3Cancer PathwayFinder

Endothelial Cell BiologyNF-κB Signaling PathwayTumor Metastasis

TGFβ / BMP SignalingChemokines Breast Cancer & Estrogen Receptor

Notch SignalingCommon CytokinesHuman miRNA Array (NEW!)

Wnt SignalingTh17 for Inflammation (NEW!)Cell Cycle

Stem CellsInflammatory CytokinesApoptosis

Development & Stem CellsCytokines & InflammationCancer and Apoptosis

~ 100 different pathways for Human, Mouse, Rat, Mon key and Fly.


.Biologically relevant gene content

� Not simply biochemical pathways or kinase cascades� Published association with the biological or disease

pathway� Specific gene information is gathered from a large

number of different overlapping sources including:- Multiple Publicly Accessible Databases- Text Mining Relevant Literature

.Technically relevant gene content � Use genes that are regulated at the mRNA level� Specific feedback from thought leaders

Genes with High Relevance

How Genes on PCR Arrays Are Selected


Customizable PCR Arrays

.Analyze the Genes Most Important.To Your Research

�Available for any real-time PCR machine.

�Wet-Bench Validated design and performance.

�2 to 3 week turn around time.

�Same Data Analysis as Catalogued Arrays


PCR Arrays for All Biomedical Researchers~ 100 different pathways for Human, Mouse, Rat, Mon key and Fly.

Cancer Research

� Angiogenesis� Epithelial to Mesenchymal Transition� Tumor Metastasis� Cancer Drug Resistance� p53 Signaling Pathway� Wnt Signaling Pathway� Cell Cycle� Breast Cancer and Estrogen Receptor Signaling� DNA Damage Signaling Pathway� MAP Kinase Signaling Pathway� Angiogenic Growth Factors and Inhibitors� Protein Phosphatases� PI3K-AKT Signaling Pathway

What are the gene expression differences between a metastatic and non-metastatic

Breast Tumor?

Research Question:


Application Example Pathway Focused Analysis between metastatic and non -metastatic tumors

What is the gene expression differences between a metastatic and non-metastatic Breast Tumor?

Tumor Metastasis PCR Array:• Cell Adhesion• Matrix Metalloproteinases• MMP Inhibitors• Cell Cycle Regulatory Genes• Cell Cycle Arrests and Checkpoint genes• Negative Regulators of Cell Proliferation• Positive Regulators of Cell Proliferation• Growth Factors and Hormones• Cytokines and Chemokines• Receptors• Pro-Apoptosis • Anti-Apoptosis • Transcription Factors

Run 3 PCR Arrays for each sample to calculate FC (and p value) using the ∆∆Ct method


FGFR4

MMP9

ETV4

MMP10

MMP2

MMP3

MMP7

Scatter Plot

UP REGULATED

DOWN REGULATED

Log 10 2-∆∆∆∆C(t) Breast Tumor (non-metastatic)

Log

102- ∆∆ ∆∆

C(t

)B

reas

t Tum

or (

met

asta

tic)

Scatter Plot Result


FGFR4

MMP9

ETV4 MMP10

MMP2

MMP3

MMP7

UP REGULATEDDOWN REGULATED

Volcano Plot

Sta

tistic

al S

igni

fican

ce

Log 2 Fold Change

Log

10(P

-val

ue)

Volcano Plot Result


Seminar Overview





Modifications



Cancer Research

Apoptosis

Cell Cycle

Inflammation

ECM/Adhesion

Neuroscience

Signal Transduction




What Is Micro RNA?

.Endogenously expressed small functional RNAs (~ 21- 23 nt)

.Regulate mRNA expression post-transcriptionally� Primarily translation inhibition, but also mRNA degradation

Only partial sequence complementarity required� One miRNA can regulate multiple mRNA� One mRNA can be regulated by multiple miRNA

.Another layer of complexity for regulating gene exp ression

.


miRNAs as Biomarkers in Cancer

Is there specific miRNAs expression differences in Human Colon tumors versus normal adjacent tissue?

Extraction of total RNA

miRNA miScript miRNA PCR ARRAYS

Normal Colon or Colon Tumor Tissue

QIAGENmiRNeasy Mini Kit


miRNA Biosynthetic Pathway

Nucleus

Dicer

miRNA-RISC

miRNA target recognition

Translation InhibitionMessage Turnover

pri-miRNA

Mature miRNAP

Drosha

pre-miRNA miRNA

miRNA gene

P

RISC


miScript miRNA PCR Arrays

.cDNA Synthesis � 1 hours

.Load Plates (Preferably with 8-Channel Pipettors)

� 2 minutes

.Run 40 cycle qPCR Program � 2 hours

.Upload and Analyze Data� 15 minutes


Anatomy of a catalogued miRNA PCR Array

.84 Pathway-Specific miRNAs

.miRNA isolation control n=2

.6 “Housekeeping”

.snRNAs

.miRNA Reverse Transcription Controls (miRTC) n=2

.Positive PCR Controls (PPC) n=2

PPCMi-

RTCPPC

Mi-RTC

RNU6-2

SNORD96A

SNORD95

SNORD72

miR-142-5p

miR-16

miR-142-3p

miR-21

miR-15a

miR-29b

Let-7a

miR-126

miR-143

miR-27a

miR-9

miR-26a

Let-7b

Let-7f

miR-24

miR-30e

miR-181a

miR-29a

miR-124

miR-144

miR-30d

miR-19b

miR-22

miR-122

miR-150

miR-32

miR-155

miR-140-5p

miR-125b

miR-141

miR-92a

miR-424

miR-191

miR-17

miR-130a

miR-20a

miR-27b

miR-26b

miR-146a

miR-200c

miR-99a

miR-19a

miR-23a

miR-30a

Let-7i

miR-93

miR-106b

Let-7c

miR-101

Let-7g

miR-425

miR-15b

miR-28-5p

miR-18a

miR-25

miR-23b

miR-302a

miR-186

miR-29c

miR-7

Let-7d

miR-30c

miR-181b

miR-223

miR-320

miR-374a

miR-151-5p

Let-7e

miR-374b

miR-196b

miR-140-3p

miR-100

miR-103

miR-96

miR-302b

miR-194

miR-125a-5p

miR-423-5p

miR-376c

miR-195

miR-222

miR-28-3p

miR-128a

miR-302c

miScript miRNA PCR Array Human miFinder (MIHS-001Z)

Cel-miR-39

Cel-miR-39

SNORD61

SNORD68

The miRNA PCR Arrays and reagents are intended for molecular biology applications. This product is not intended for the diagnosis, prevention or treatment of disease.


miScript miRNA RNA PCR Arrays:Available for Human, Mouse, Rat and Dog, Rhesus Mac que

miRNome (miRBase V16) Human Mouse Rat Dog

miRNome (miRBase V16) 384 Well Format Human Mouse Rat Dog

miFinder Human Mouse Rat Dog Rhesus Macaque

miFinder 384HC Human Mouse

Brain Cancer Human Mouse Rat

Breast Cancer Human Mouse Rat

Cancer PathwayFinder Human Mouse Rat

Cell Differentiation & Development Human Mouse Rat

Immunopathology Human Mouse Rat

Inflammatory Response and Autoimmunity Human Mouse Rat

Neurological Development & Disease Human Mouse Rat

Ovarian Cancer Human Mouse Rat

Prostate Cancer Human Mouse Rat

Serum & Plasma Human Mouse Rat

T-Cell & B-Cell Activation Human Mouse Rat

miRNA QC Human Mouse Rat Dog


miRNAs as Biomarkers in Cancer


miRNA


miScript Human CancerPathwayFindermiRNA PCR Array




miScript Human CancerPathwayfinder PCR Array:Many Cancer-Specific miRNA Are Up-regulated in the

Colon Tumor.

Colon Cancer Biomarkers


What about targets of the miRNAs?Is it possible to measure mRNA from the same sample ?

Colon Cancer Biomarkers


Use PCR Arrays to Measure Pathway Specific Gene Exp ression



miRNA


miScriptmiRNA ARRAYS


RT2 ProfilerPCR ARRAYS

Archive “large” mRNA fractionFor use on PCR Arrays


Seminar Overview




lines and Normal Breast Tissue� Profiling Histone Modification on CDKN1A



Cancer Research

Apoptosis

Cell Cycle

Inflammation

ECM/Adhesion

Neuroscience

Signal Transduction




– Important genes (i.e. tumor suppressors) are silenc ed

– All cellular pathways related to cancer can be affe cted

Adapted from Herman,

J. and Baylin, S. N. Engl.

J. Med. 2003

Normal

Cancer

1111 2222 3333

1111 2222 3333

Promoter RegionPromoter RegionPromoter RegionPromoter RegionExpression

No Expression

• CpG islands: CpG-rich regions in human gene promote rs– Most CpG dinucleotides are methylated outside of promoter regions

– Healthy/normal cells: rarely methylated

– Cancer cells: hypermethylated, leading to transcriptional silencing

CpG Islands and Methylation


Background DNA Methylation

.Biological Importance� Role in normal development and also disease progression� Potentially silences critical tumor suppressors� Involves all cellular pathways� Stable/Covalent modificaton which can be detected in heterogeneous

fluids� Promising biomarker for early detection and predicting prognosis


DNA Methylation and Transcriptional Repression

Blood, 93:4059-4070, 1999


Methylation in Oncogenesis: Study Design

Obtained genomic DNA from Human Breast Cancer Cell lines (ATCC)

Normal Breast Tissue (Capital Bioscience)

Bioinformatics text mining:Custom PCR Arrays:��genes hypermethylated in Breast Cancer with high fr equencies

What are the difference in the Methylation status o f breast cancer

associated genes among commonly used Breast Cancer Cell lines?


EpiTect Methy lI PCR Arrays (24 and 96 gene panels)

Cancer Related� Breast Cancer

� Epithelial to Mesenchymal Transition

� Gastric Cancer

� Liver Cancer

� Lung Cancer

� Prostate Cancer

� Colon Cancer

� Leukemia & Lymphoma

� Tumor Suppressor Genes

Simultaneously analyze the DNA methylation status of 22- or 94-gene panels associated with specific cancer types, other diseases or biological pathways.

Pathway-Focused Methyl qPCR Arrays• Apoptosis• DNA Repair• Stem Cell Transcription Factors• Inflammatory Response• T Cell Activation• Cytokine Production• Tumor Suppressor Genes• Homeobox (HOX) Genes• Polycomb (PcG) Genes• Cell Cycle• Toll-Like Receptor Signaling• TGF-Beta/BMP Signaling• Wnt Signaling

96 and 384 well qPCR Arrays-Human and Mouse

Custom Arrays and Custom Assays

Available for most CpG island-containing promoter in the human, mouse, or rat genome.

http://www.sabiosciences.com/dna_methylation_custom_PCRarray.php


DNA Methylation PCR Array Protocol Overview

(0.5 – 4 ug of Genomic DNA)

24 gene- Signature Panel





Data Analysis using downloadable Excel TemplatesAccurate calculates ∆∆∆∆Ct values and converts to %


EpiTect Methyl II Biomarker Discovery

EpiTect Methtl II PCR Arrays can be effectively used to identify novel hypermethylated biomarkers.


Use Epitect Pyrosequencing Assays to quantitatively identify Methylation at the single nucleotide level.

Measure gene expression using cataloged or custom RT2 Profiler PCR Arrays

EpiTect Methtl II PCR Arrays can be effectively used to identify novel hypermethylated biomarkers.

EpiTect Methyl II Biomarker Discovery


Seminar Overview







Cancer Research

Apoptosis

Cell Cycle

Inflammation

ECM/Adhesion

Neuroscience

Signal Transduction




What IS ChIP?

What is ChIP?.Chromatin Immuno- Precipitation.Method to examine in vivo protein-DNA interactions.Applications:

� Transcription Factors, Modified Histones, Other nuclear factors

ChIP-qPCR is Chromatin Immunoprecipitation with qPCR Detection and Quantification


Applications for ChIP

�Where does my Transcription Factor (or any protein that binds DNA) interact with gDNA?

�Example: Which p53 binding site is being used?�Use Custom ChIP PCR Array for multiple “tiles” within 1 gene�Or use individual ChIP qPCR Assay

�What is the chromatin structure? Is it open or closed? (histone modifications)�Example: Can p53 bind to this site?�Use Cataloged Array for pathway (84 genes looking at +1 “tile”�Or Use individual qPCR Assay/ Custom PCR Array


ChIP PCR Arrays: 2 different applications and Layou ts

Profiling 1 gene with 30 tilesWhat is the chromatin structure for the entire promoter region

Profiling 1 tile (+1 tile) for 84 genes in a Pathway

•Tumor Suppressor & Oncogenes •Cancer Drug Targets•DNA Repair•Cell Cycle•Stem Cell Transcription Factors•Inflammatory Response•T Hellper Cell Differentiation•Polycomb & Trithorax Target Genes•Polycomb & Trithorax Complexes•Homeobox (HOX) Genes


Chromatin Immunoprecipitation Workflow

XX

X

X-LinkLyseFragment IP

Reverse X-LinkPurify DNA

Stimulus

Input Anti-TF NIS

ChIP-qPCR

Real-TimePCR Primers


qPCR Assay Design: Tiling Scheme

.Thirty (30) 1-kb tiles from -20 kb to +10 kb relative to each TSS

.Accommodate every human, mouse and rat gene promoter

.Balance Between Sensitivity & Resolution

.Quality Controlled for Specificity & Amplification Efficiency

. qPCR Assay & Amplicon Amplicon Coverage Range (Tile)

Proximal Promoter

TSS (+1)mRNA

gDNA

Structural Gene

Distal Promoter

1 kb 1 kb1 kb 1 kb1 kb


qPCR Assay Design: Tiling Schemefor Pathway Catalogued Arrays

.Tiles +1kb relative to each TSS for 84 genes in a pathway

.Quality Controlled for Specificity & Amplification Efficiency

.Use the +1kb tile as a surrogate for promoter region to know transcriptional status

.Use many genes to understand pathway

.Correlate with gene expression

. qPCR Assay & Amplicon Amplicon Coverage Range (Tile)

Proximal Promoter

TSS (+1)mRNA

gDNA

Structural Gene

Distal Promoter

1 kb 1 kb1 kb 1 kb1 kb

84 Genes with only +1 Tile


Modified Histone Distribution Across a Promoter

Histone markers for actively transcribed genes (H3Ac and H3K4me2) but not for transcriptionally inactive genes (H3K27me3) surround the CDKN1A gene making it available to p53 regulation.

Custom ChIP PCR Array for Entire CDKN1A Gene


Seminar Overview







Cancer Research

Apoptosis

Cell Cycle

Inflammation

ECM/Adhesion

Neuroscience

Signal Transduction




PCR Array Summary

.Complete System (From Sample to Fold Change)� Five-component system: Sample Isolation, PCR arrays, First strand

(OR DNA RE Kit), master mix, and data analysis software

Breadth of Content �CATALOGED Pathways or customizable� Gene Expression� MicroRNA Expression � DNA Methylation � Chromatin Immunoprecipitation (histone modifications/TF binding)

Validated Real-Time PCR Performance� Wet-Bench tested qPCR Assays for Sensitivity, Specificity, and

Amplification Efficiency on every qPCR manufactured.

.Final Benefit to Researcher:

. Platform technology for any qPCR machine in any laboratory


Need More Info? Product Support Tools

www.sabiosciences.com

Global Technical Support Email: Support@SABioscienc es.com


Thank you for attending!

Questions, Comments, Suggestions, Concerns?

[email protected]

Questions, Comments, Concerns?US Applications Support

[email protected]

Questions, Comments, Concerns?Global Applications Support

[email protected]

epigenetics 2013

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