<p>It's usually CNV callers that make use of Tumour/Normal WGS pairs to estimate purity. It can also be done with WES (exome) Tumour/Normal pairs.</p>

<p>There are several tools out there, I have some experience with the one written by Illumina (public on Github):</p>

<p><a href="https://github.com/Illumina/canvas" rel="nofollow noreferrer">https://github.com/Illumina/canvas</a></p>

<p>It requires realigning things with bowtie2, so I don't think it can take existing data aligned with other aligners. Not sure why.</p>

CC BY-SA 3.0
2017-06-01T13:44:50.700Z
Where are you getting the bowtie2 requirement from? The readme examples all use isaac bams
blmoore
CC BY-SA 3.0
2017-06-01T13:48:29.177Z
Section 5.1 of the pdf documentation (CanvasBin): `Canvas has been validated using BAM files created using the Isaac and Bowtie aligners`. I guess it means that it may work with other aligners, but hasn't been validated.
719016
CC BY-SA 3.0
2017-06-01T14:03:30.563Z
Thanks for your answer. Since this is primarily a CNV caller, do you think that mean it requires rearrangements to estimate admixture amount?
S. DiLorenzo
CC BY-SA 3.0
2017-06-01T13:38:07.977Z
2017-06-01T13:38:07.977Z
719016
<p><a href="https://github.com/mathieu-lemire/celluloid_0.11" rel="nofollow noreferrer">Celluloid</a> emits copy number profiles and tumour purity / ploidy information.  There's a nice tutorial https://github.com/mathieu-lemire/celluloid_0.11_tutorial. One thing to keep in mind is that celluloid will find multiple solutions and taking advantage of its plotting tools is essential to determining which solution is correct. Typically the first solution is correct, but occasionally it may not be.</p>

<p>Another tool similar is <a href="http://genome.cshlp.org/content/early/2014/07/24/gr.180281.114" rel="nofollow noreferrer">TITAN</a>, which may also require hand annotated the ideal solution.</p>

CC BY-SA 3.0
2017-06-04T13:37:19.093Z
2017-06-04T13:37:19.093Z
GWW
<p>I have previously estimated tumour purity with the <a href="http://dna-discovery.stanford.edu/software/expands/" rel="nofollow noreferrer">EXPANDS</a> an inferred tumour heterogeneity program which is designed to calculate the number of clonal subpopulations in matched tumour/normal samples.  The purity is essentially the size of the largest subpopulation identified in that sample - this is discussed in the programs <a href="http://dna-discovery.stanford.edu/software/expands/expands_faq.html" rel="nofollow noreferrer">FAQ</a>.  In addition to a matched tumour / normal exome or genome sequencing you'll also need match somatic copy number as a seg file as input.  Other programs also exist for this sort of inferred heterogeneity analysis - some of which may also give you a measure of purity are: <a href="https://www.nature.com/nbt/journal/v30/n5/full/nbt.2203.html" rel="nofollow noreferrer">Absolute</a>, <a href="https://genomebiology.biomedcentral.com/articles/10.1186/gb-2013-14-7-r80" rel="nofollow noreferrer">ThetA</a>, <a href="http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003665" rel="nofollow noreferrer">SciClone</a>, <a href="https://genomebiology.biomedcentral.com/articles/10.1186/s13059-014-0473-4" rel="nofollow noreferrer">CHAT</a>, <a href="https://www.nature.com/nmeth/journal/v11/n4/full/nmeth.2883.html" rel="nofollow noreferrer">PyClone</a> and <a href="http://www.pnas.org/content/113/37/E5528.full" rel="nofollow noreferrer">Canopy</a>. A more complete list looks to be <a href="https://omictools.com/tumor-purity-and-heterogeneity-category" rel="nofollow noreferrer">here</a>.  </p>

<p>The only other thing I'd suggest is have an estimate via some orthogonal measure of the purity to try at least judge how the different methods are performing with you data, <em>e</em>.<em>g</em>. you might have clonality indications from <a href="https://en.wikipedia.org/wiki/Cytogenetics" rel="nofollow noreferrer">cytogenetics/FISH</a> or histology work, or perhaps <a href="https://en.wikipedia.org/wiki/Flow_cytometry#Fluorescence-activated_cell_sorting_.28FACS.29" rel="nofollow noreferrer">FACS</a>.  Picking samples known to be pure / impure via one or more of these might help you get a handle on how well various methods are performing.</p>

<p>As regards estimation without a normal sample the only program which looks like it might help is <a href="https://github.com/DeveauP/QuantumClone/" rel="nofollow noreferrer">QuantumClone</a>, but that requires more than one tumour sample form said patient either spatially or temporally distinct to perform the analysis. </p>

<p>Also If you have low coverage DNA sequencing <a href="http://www.precancer.leeds.ac.uk/software-and-datasets/cnanorm/" rel="nofollow noreferrer">CNAnorm</a> looks like it could be useful with just a single sample. </p>

CC BY-SA 3.0
2017-06-03T16:18:46.493Z
2017-06-03T16:18:46.493Z
Matt Bashton
<p>Can anyone recommend a good tool for estimating the tumor content given a matched tumor and normal file for DNA NGS whole genome sequencing data or whole exome data?</p>

<p>Is it possible to estimate this without a normal sample as well?</p>

CC BY-SA 3.0
2017-06-01T13:21:36.983Z
N.B., I've edited your post to include the word "admixture", which is what you should search for the find relevant tools.
Devon Ryan
CC BY-SA 3.0
2017-06-01T13:36:07.737Z
Great, might as well make it purity/contamination/admixture then =). Many names for same meaning.
S. DiLorenzo
CC BY-SA 3.0
2017-06-01T13:37:02.283Z
Yeah, but you'll get a lot more relevant hits with "cancer admixture estimate" :)
Devon Ryan
CC BY-SA 3.0
2017-06-01T16:26:12.000Z
I would suggest to change "admixture", which is common in population genetics for genetic exchange between populations to "cell admixture".
Kamil S Jaron
<cancer><wgs>
Tumor purity/contamination/admixture estimation
# Tumor purity/contamination/admixture estimation

(Asked by: username_0 on 2017-06-01)

Can anyone recommend a good tool for estimating the tumor content given a matched tumor and normal file for DNA NGS whole genome sequencing data or whole exome data?

Is it possible to estimate this without a normal sample as well?

**Tags:** cancer, wgs
> **Comments:**
> **username_1**: N.B., I've edited your post to include the word "admixture", which is what you should search for the find relevant tools.  
> **username_0**: Great, might as well make it purity/contamination/admixture then =). Many names for same meaning.  
> **username_1**: Yeah, but you'll get a lot more relevant hits with "cancer admixture estimate" :)  
> **username_2**: I would suggest to change "admixture", which is common in population genetics for genetic exchange between populations to "cell admixture".  

---

## 3 answers

### Answer by username_6 on 2017-06-03. Score: 3 | Accepted answer

I have previously estimated tumour purity with the [EXPANDS](http://dna-discovery.stanford.edu/software/expands/) an inferred tumour heterogeneity program which is designed to calculate the number of clonal subpopulations in matched tumour/normal samples. The purity is essentially the size of the largest subpopulation identified in that sample - this is discussed in the programs [FAQ](http://dna-discovery.stanford.edu/software/expands/expands_faq.html). In addition to a matched tumour / normal exome or genome sequencing you'll also need match somatic copy number as a seg file as input. Other programs also exist for this sort of inferred heterogeneity analysis - some of which may also give you a measure of purity are: [Absolute](https://www.nature.com/nbt/journal/v30/n5/full/nbt.2203.html), [ThetA](https://genomebiology.biomedcentral.com/articles/10.1186/gb-2013-14-7-r80), [SciClone](http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003665), [CHAT](https://genomebiology.biomedcentral.com/articles/10.1186/s13059-014-0473-4), [PyClone](https://www.nature.com/nmeth/journal/v11/n4/full/nmeth.2883.html) and [Canopy](http://www.pnas.org/content/113/37/E5528.full). A more complete list looks to be [here](https://omictools.com/tumor-purity-and-heterogeneity-category).

The only other thing I'd suggest is have an estimate via some orthogonal measure of the purity to try at least judge how the different methods are performing with you data, *e*.*g*. you might have clonality indications from [cytogenetics/FISH](https://en.wikipedia.org/wiki/Cytogenetics) or histology work, or perhaps [FACS](https://en.wikipedia.org/wiki/Flow_cytometry#Fluorescence-activated_cell_sorting_.28FACS.29). Picking samples known to be pure / impure via one or more of these might help you get a handle on how well various methods are performing.

As regards estimation without a normal sample the only program which looks like it might help is [QuantumClone](https://github.com/DeveauP/QuantumClone/), but that requires more than one tumour sample form said patient either spatially or temporally distinct to perform the analysis.

Also If you have low coverage DNA sequencing [CNAnorm](http://www.precancer.leeds.ac.uk/software-and-datasets/cnanorm/) looks like it could be useful with just a single sample.


---

### Answer by username_3 on 2017-06-01. Score: 2

It's usually CNV callers that make use of Tumour/Normal WGS pairs to estimate purity. It can also be done with WES (exome) Tumour/Normal pairs.

There are several tools out there, I have some experience with the one written by Illumina (public on Github):

<https://github.com/Illumina/canvas>

It requires realigning things with bowtie2, so I don't think it can take existing data aligned with other aligners. Not sure why.

> **Comments:**
> **username_4**: Where are you getting the bowtie2 requirement from? The readme examples all use isaac bams  
> **username_3**: Section 5.1 of the pdf documentation (CanvasBin): `Canvas has been validated using BAM files created using the Isaac and Bowtie aligners`. I guess it means that it may work with other aligners, but hasn't been validated.  
> **username_0**: Thanks for your answer. Since this is primarily a CNV caller, do you think that mean it requires rearrangements to estimate admixture amount?  

---

### Answer by username_5 on 2017-06-04. Score: 1

[Celluloid](https://github.com/mathieu-lemire/celluloid_0.11) emits copy number profiles and tumour purity / ploidy information. There's a nice tutorial https://github.com/mathieu-lemire/celluloid\_0.11\_tutorial. One thing to keep in mind is that celluloid will find multiple solutions and taking advantage of its plotting tools is essential to determining which solution is correct. Typically the first solution is correct, but occasionally it may not be.

Another tool similar is [TITAN](http://genome.cshlp.org/content/early/2014/07/24/gr.180281.114), which may also require hand annotated the ideal solution.


---

