Difference between revisions of "Estimating Gene Count Talk"

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(Created page with "Estimating gene count = Estimating Gene Count = How many reads are overlapping genomic features? - or - Can we confidently assign each read to a feature/transcript/gene? Not...")
 
 
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Estimating gene count
 
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= Estimating Gene Count =
 
= Estimating Gene Count =
 
How many reads are overlapping genomic features?
 
How many reads are overlapping genomic features?
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= Multi mapping reads =
 
= Multi mapping reads =
 
* Unsolved problem:
 
* Unsolved problem:
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– Can account for 10-30% of reads
+
:- this can account for 10-30% of reads
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GeneA – chr11
 
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GeneB – chr5
 
−
 
 
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– Ignore them … (decrease sensitivity)
 
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– Weighted assignment
 
−
 
 
−
= Multi mapping reads =
 
−
* Unsolved problem:
 
−
– Can account for 10-30% of reads
 
−
GeneA – chr11
 
−
GeneB – chr5
 
−
 
 
−
Solution is to use longer reads
 
−
– Ignore them … (decrease sensitivity)
 
−
– Weighted assignment
 
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= Transcripts/Genes =
 
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* Transcripts/Isoforms or Genes
 
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T1
 
−
GeneA
 
−
 
 
−
= Transcripts/Genes =
 
−
* Transcripts/Isoforms or Genes
 
−
T1
 
−
T2
 
−
 
 
−
GeneA
 
−
 
 
−
T3
 
  
−
= Transcripts/Genes =
+
[[File:unsolved.png]]
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* Transcripts/Isoforms or Genes
 
−
T1
 
−
T2
 
  
−
GeneA
+
* Ignore them, but then again this decreases sensitivity
 +
* Weighted assignment
  
−
= Transcripts/Genes =
+
Of course, longer reads would solve this problem.
−
* Transcripts/Isoforms or Genes
 
−
T1
 
−
T2
 
  
−
GeneA
+
= One transcript, one set of reads =
  
−
T3
+
[[File:t1.png]]
  
−
= Transcripts/Genes =
+
= Two transcripts, another set of reads =
−
* Transcripts/Isoforms or Genes
 
−
T1
 
−
T2
 
  
−
GeneA
+
[[File:t1t2.png]]
  
−
T3
+
= Aggregation to Gene-level 1 =
  
−
= Transcripts/Genes =
+
[[File:t1t2aggreg.png]]
−
* Transcripts/Isoforms or Genes
 
−
T1
 
−
T2
 
  
−
GeneA
+
= Third transcript, another set of reads =
  
−
T3
+
[[File:t1t2t3.png]]
  
−
= Transcripts/Genes =
+
= Aggregation to Gene-level 2 =
−
* Transcripts/Isoforms or Genes
 
−
T1
 
−
T2
 
  
−
GeneA
+
[[File:t1t2t3aggreg.png]]
−
 
 
−
T3
 
−
 
 
−
Gene level is aggregating transcripts
 
−
Transcript level needs longer reads
 
  
 
= HTSeq-count =
 
= HTSeq-count =
  
 
* Designed for RNA-Seq counting
 
* Designed for RNA-Seq counting
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* Simple to use (especially since v0.6.0)
 
 
* Work at gene level
 
* Work at gene level
 
* Remove multi-mapped reads
 
* Remove multi-mapped reads
 
* Several modes to resolve remaining uncertainty
 
* Several modes to resolve remaining uncertainty
  
−
= HTSeq-count =
+
[[File:htseq.png]]
−
 
 
−
= Probabilistic approach =
 
  
−
Cufflink
+
= HTSeq-count modes =
  
−
cuffdiff
+
[[File:htcats.png]]
  
−
= Probabilistic approach =
+
= Probabilistic approach 1 =
  
−
Cufflinks:
+
* Cufflinks
−
Reconstruct the transcripts from the data and annotation
+
:- Reconstruct the transcripts from the data and annotation
  
−
= Probabilistic approach =
+
[[File:minpath.png]]
−
Cufflinks:
 
−
Reconstruct the transcripts from the data and annotation
 
  
−
Cuffdiff:
+
= Probabilistic approach 2 =
−
Assign each read/fragment to a transcript
+
* Cuffdiff:
−
with a probability maximum likelihood.
+
:- Assign each read/fragment to a transcript with a probability maximum likelihood.
  
−
= Probabilistic approach =
+
[[File:isolik.png]]
−
Cufflinks:
 
−
Reconstruct the transcripts from the data and annotation
 
−
Pros:
 
−
- Better methodology
 
−
- Integrated package (ease of use)
 
−
Cons:
 
−
Cuffdiff:
 
−
- Do not support alternative experiment design
 
−
- History of heterogeneous results/versions
 
−
* Assign each read/fragment to a transcript with a probability maximum likelihood.
 

Latest revision as of 13:34, 9 May 2017

Estimating Gene Count

How many reads are overlapping genomic features? - or - Can we confidently assign each read to a feature/transcript/gene? Not so simple.

We also have:

  • Multi mapping reads
  • Overlapping genes/transcripts

Two approaches:

  • Focus on what’s known with certainty
  • Probabilistic

Multi mapping reads

  • Unsolved problem:
- this can account for 10-30% of reads

Unsolved.png

  • Ignore them, but then again this decreases sensitivity
  • Weighted assignment

Of course, longer reads would solve this problem.

One transcript, one set of reads

T1.png

Two transcripts, another set of reads

T1t2.png

Aggregation to Gene-level 1

T1t2aggreg.png

Third transcript, another set of reads

T1t2t3.png

Aggregation to Gene-level 2

T1t2t3aggreg.png

HTSeq-count

  • Designed for RNA-Seq counting
  • Work at gene level
  • Remove multi-mapped reads
  • Several modes to resolve remaining uncertainty

Htseq.png

HTSeq-count modes

Htcats.png

Probabilistic approach 1

  • Cufflinks
- Reconstruct the transcripts from the data and annotation

Minpath.png

Probabilistic approach 2

  • Cuffdiff:
- Assign each read/fragment to a transcript with a probability maximum likelihood.

Isolik.png