immunological bioinforma cs automated analysis of facs data

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Immunological Bioinforma/cs Automated analysis of FACS data Ali Al9ntaş (slides from Juliet Frederiksen)

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Page 1: Immunological Bioinforma cs Automated analysis of FACS data

Immunological  Bioinforma/cs  

 

Automated  analysis  of  FACS  data  

Ali  Al9ntaş  

 

(slides  from  Juliet  Frederiksen)  

Page 2: Immunological Bioinforma cs Automated analysis of FACS data

Overview

1.  Introduc/on  to  Flow  Cytometry    

2.  Automated  analysis  of  Flow  Cytometry  data  

Page 3: Immunological Bioinforma cs Automated analysis of FACS data

Introduc/on  to  Flow  Cytometry  

Page 4: Immunological Bioinforma cs Automated analysis of FACS data

Quick  introduc/on  to  Flow  Cytometry  

First commercial flow cytometer: PDP 11 computer (1969)

Let’s start with a little walk down memory lane…

Page 5: Immunological Bioinforma cs Automated analysis of FACS data

Introduc/on  to  Flow  Cytometry  

Schematic of a modern Flow Cytometer

!"#$%%&'()&"*+&,"#*

-.&/*01(23$%*

Figure  adapted  from  Introduc2on  to  Flow  Cytometry  Data  Analysis,  Invitrogen    

Page 6: Immunological Bioinforma cs Automated analysis of FACS data

Introduc/on  to  Flow  Cytometry  

At the interrogation point…

Page 7: Immunological Bioinforma cs Automated analysis of FACS data

Introduc/on  to  Flow  Cytometry  

Up close and personal…

Page 8: Immunological Bioinforma cs Automated analysis of FACS data

Introduc/on  to  Flow  Cytometry  

Case story: You want to study the state of HIV infected individuals immune system. To do this you identify 8 cellular markers (antigens) that would give you a good representation of what you want to study. For each of these 8 markers you find fluorochrome-labelled mAbs. Then the “level” of each colour is measured on each cell as it passes by the laser.

Page 9: Immunological Bioinforma cs Automated analysis of FACS data

Introduc/on  to  Flow  Cytometry  

The types of signal detected by the flow cytometer

Figure  adapted  from  Introduc2on  to  Flow  Cytometry  Data  Analysis,  Invitrogen    

Page 10: Immunological Bioinforma cs Automated analysis of FACS data

Introduc/on  to  Flow  Cytometry  

Schematic of a modern Flow Cytometer

!"#$%%&'()&"*+&,"#*

-.&/*01(23$%*

Figure  adapted  from  Introduc2on  to  Flow  Cytometry  Data  Analysis,  Invitrogen    

Page 11: Immunological Bioinforma cs Automated analysis of FACS data

Introduc/on  to  Flow  Cytometry  

Filters

Figure  adapted  from  Introduc2on  to  Flow  Cytometry,  Abcam    

BP  =  Band  pass  

SP  =  Short  pass  

LP  =  Long  pass  

Dichroic  =  45  degree  angle  

Figure  from  Flow  Cytometry  -­‐  A  Basic  Introduc2on,  Michael  G  Ormerod      

 

Page 12: Immunological Bioinforma cs Automated analysis of FACS data

Introduc/on  to  Flow  Cytometry  

More details

Figure  adapted  from  Introduc2on  to  Flow  Cytometry  Data  Analysis,  Invitrogen    

Page 13: Immunological Bioinforma cs Automated analysis of FACS data

Introduc/on  to  Flow  Cytometry  

Spectral Overlap

Page 14: Immunological Bioinforma cs Automated analysis of FACS data

Introduc/on  to  Flow  Cytometry  

Compensation

Spillover Fluorescence

FL-1 FL-2

A - 17%

B 6% -

Page 15: Immunological Bioinforma cs Automated analysis of FACS data

Introduc/on  to  Flow  Cytometry  

Now comes the interesting stuff!

Page 16: Immunological Bioinforma cs Automated analysis of FACS data

Introduc/on  to  Flow  Cytometry  

What does the output from the flow cytometer look like?

Page 17: Immunological Bioinforma cs Automated analysis of FACS data

Introduc/on  to  Flow  Cytometry  

What does the output from the flow cytometer look like?

Page 18: Immunological Bioinforma cs Automated analysis of FACS data

Introduc/on  to  Flow  Cytometry  A

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What do you do with the output?

Page 19: Immunological Bioinforma cs Automated analysis of FACS data

Quick  introduc/on  to  Mass  Cytometry  

A  deep  profiler's  guide  to  cytometry,  Trends  Immunol.,  Bendall  et  al.  

Page 20: Immunological Bioinforma cs Automated analysis of FACS data

Automated  FCM  data  analysis  

Page 21: Immunological Bioinforma cs Automated analysis of FACS data

Quick  introduc/on  to  Flow  Cytometry  

Let’s start with a little walk down memory lane…

A  deep  profiler's  guide  to  cytometry,  Trends  Immunol.,  Bendall  et  al.  

Page 22: Immunological Bioinforma cs Automated analysis of FACS data

Automated  FCM  data  analysis  

Typical scenario with FCM data analysis…

Page 23: Immunological Bioinforma cs Automated analysis of FACS data

Automated  FCM  data  analysis  

Tools available on internet

•  NetFCM •  SPADE •  SPICE •  FLOCK •  flowCore

Page 24: Immunological Bioinforma cs Automated analysis of FACS data

Automated  FCM  data  analysis  

Let’s check out NetFCM

What is NetFCM? An online tool for the analysis of FCM data sets. What is the input to NetFCM? Compensated FCS files, marker information and gating strategy.

Page 25: Immunological Bioinforma cs Automated analysis of FACS data

Automated  FCM  data  analysis  

Let’s check out NetFCM

What type of analysis does NetFCM perform? (1)   Principle component analysis

Page 26: Immunological Bioinforma cs Automated analysis of FACS data

Automated  FCM  data  analysis  

Let’s check out NetFCM

What type of analysis does NetFCM perform? (2) K-means clustering

Page 27: Immunological Bioinforma cs Automated analysis of FACS data

Automated  FCM  data  analysis  

Let’s check out NetFCM

What type of analysis does NetFCM perform? (3) Extreme Value Detection

Page 28: Immunological Bioinforma cs Automated analysis of FACS data

Automated  FCM  data  analysis  

Let’s check out FLOCK

Page 29: Immunological Bioinforma cs Automated analysis of FACS data

Automated  FCM  data  analysis  

Let’s check out FLOCK

FLOCK is an online tool that uses a density-based clustering approach to algorithmically identify biologically relevant cell populations.

Page 30: Immunological Bioinforma cs Automated analysis of FACS data

Automated  FCM  data  analysis  

Let’s check out FLOCK

Page 31: Immunological Bioinforma cs Automated analysis of FACS data

Automated  FCM  data  analysis  

http://imcportal.org/education/video/martin-zand-visualization-of-high-dimensional-data

Page 32: Immunological Bioinforma cs Automated analysis of FACS data

Automated  FCM  data  analysis  

An overall pipeline for R/Bioconductor

Figure  adapted  from  Introduc2on  to  Flow  Cytometry  Analysis  in  R  by  Ryan  Brinkman  (17.06.13)  

Page 33: Immunological Bioinforma cs Automated analysis of FACS data

Exercise  /me!  

 

 

 

 

 

Let’s  do  some  analysis!