Normal_contamination_estimate

[udp3f]

Hi,

I am running the snakemake pipeline for TitanCNA for tumor/normals, where my maxploidy is set for 2 (that is what we believe of our sample) and I am doing different cluster initializations. I am a bit perplexed with the normal_contamination estimate I get for ploidy2 state where the params file outputs 0.99 as the normal contamination for any fixed cluster solution, which means 0.01 is the tumor purity. The same sample when run with a max ploidy of 3 gives 0.23 as the normal contamination for cluster 1, which seems pretty close to what we expect to see. I am not sure what this difference means. If I stick to ploidy state 2 which we believe our sample is, for different cluster solutions, my tumor purity is only 1% which we can not go with. Could you please explain what this might mean.

[gavinha]

Hi @udp3f

Are you able to show a plot of one of the chromosomes so that we can see what might be happening.

Thanks,
Gavin

[udp3f]

[udp3f]

Hi Gavin,

Above is a chr10 plot for ploidy=2, cluster 1 for which normal contamination was 0.99

-Uma

[gavinha]

Hi @udp3f

The quality of the data seems really good and might not be the problem. Do you see this type of result for the rest of the chromosomes? If so, then perhaps the normal contamination estimate of 0.99 is actually reasonable?

-Gavin

[udp3f]

Hi Gavin,

The rest of the chromosomes look similar except for chr17 which has an event. Below is the figure.
However, ploidy=2, cluster=5 has a normal estimate of 0.91 for which I am attaching chr10 image below.

[gavinha]

Hi @udp3f
Based on the event in chr17, the normal estimate should not be 0.91. It should be less than 0.1.

What are the estimates for the run with initializations of ploidy=2 and number of clusters of 1 (cluster01)?

This might be an issue with the optimal solution selection.

-Gavin

[udp3f]

It is 0.99 for ploidy=2, cluster01 (for fixed cluster size =1) &
0.91 for ploidy=2, cluster05 (for fixed cluster size = 5)

[gavinha]

Something funny is going on. It must be a bug. Would it be possible for you to share the RData file for the ploidy=2, cluster01 solution? If so, please send to [email protected].

Thanks,
Gavin

[udp3f]

I mailed you the RData.

[sahilseth]

I am facing a similar issue, were there any insights from this example?

I have 3 cases where titan selects a very low purity solution. However, VAFs suggest a higher purity.

[sahilseth]

This one has a KRAS mutation with AF=0.3

Estimated purity from titan in this case, is 2.5%, however, by including CNV+SSM in phylowgs the purity comes out to be 70%.

Phi	cluster	numClust	cellPrev	purity	norm	ploidy	loglik	sdbw	opt_phi	opt_solution
2	1	1	1	2.41%	97.59%	2.042	-97664.4	1.0489	TRUE	TRUE
2	2	1	1	24.98%	75.02%	2.381	-94448	2.8469	TRUE	FALSE
2	3	1	1	24.84%	75.16%	2.4	-94403.4	2.777	TRUE	FALSE
2	4	1	1	24.91%	75.09%	2.474	-94455.4	2.7487	TRUE	FALSE
2	5	2	1     ,0.8056	29.28%	70.72%	2.456	-94267.3	2.3584	TRUE	FALSE
2	6	3	1     ,0.8643,0.785	23.74%	76.26%	1.775	-93637.1	2.46	TRUE	FALSE
2	7	4	1     ,0.8667,0.7883,0.5433	23.63%	76.37%	1.794	-93713.7	2.7261	TRUE	FALSE
2	8	2	1     ,0.8416	12.25%	87.75%	2.032	-93187.1	NA	TRUE	NA
2	9	2	1     ,0.8464	12.24%	87.76%	2.039	-93267.5	3.1268	TRUE	FALSE
2	10	2	1     ,0.8465	12.25%	87.75%	2.039	-93259	3.1161	TRUE	FALSE
3	1	1	1	25.66%	74.34%	3.088	-94954.2	2.3421	FALSE	FALSE
3	2	1	1	24.95%	75.05%	2.574	-94604.7	2.7984	FALSE	FALSE
3	3	2	1     ,0.8069	29.51%	70.49%	2.542	-94403.8	2.9229	FALSE	FALSE
3	4	3	1     ,0.8667,0.7361	32.09%	67.91%	2.539	-94362.8	2.3935	FALSE	FALSE
3	5	4	1     ,0.8645,0.7608,0.6743	32.56%	67.44%	2.496	-94212.7	2.3396	FALSE	FALSE
3	6	4	1     ,0.8185,0.7445,0.2326	31.85%	68.15%	2.281	-93328.3	2.0768	FALSE	FALSE
3	7	5	1     ,0.8977,0.7976,0.4905,0.3858	31.34%	68.66%	2.78	-95516.7	2.4976	FALSE	FALSE
3	8	4	1     ,0.7794,0.5641,0.3902	24.87%	75.13%	2.982	-96234.1	3.0184	FALSE	FALSE
3	9	3	1     ,0.7551,0.4076	11.44%	88.56%	2.581	-93950	2.8904	FALSE	FALSE
3	10	3	1     ,0.4281,0.301	10.92%	89.08%	2.46	-93488.9	3.1647	FALSE	FALSE
4	1	1	1	94.05%	5.96%	4.046	-94910.8	1.6776	FALSE	FALSE
4	2	2	1    ,0.793	42.36%	57.64%	4.119	-93931.3	1.5277	FALSE	FALSE
4	3	2	1    ,0.819	40.36%	59.64%	3.993	-93884.2	1.4405	FALSE	FALSE
4	4	3	1     ,0.8717,0.7593	41.62%	58.38%	3.981	-93809.6	1.6194	FALSE	FALSE
4	5	4	1     ,0.8622,0.7674,0.6836	41.40%	58.60%	3.962	-93801.7	1.4913	FALSE	FALSE
4	6	4	1     ,0.8626,0.7678,0.6842	41.40%	58.60%	3.961	-93818	1.5302	FALSE	FALSE
4	7	4	1     ,0.8676,0.7675,0.6903	41.07%	58.93%	3.988	-93842.2	1.438	FALSE	FALSE
4	8	4	1     ,0.8661,0.7665,0.6914	41.03%	58.97%	3.985	-93852.8	1.3104	FALSE	FALSE
4	9	4	1     ,0.8634,0.7754,0.7069	40.99%	59.01%	3.959	-93835.3	1.6504	FALSE	FALSE
4	10	4	1     ,0.863 ,0.775 ,0.7066	40.96%	59.04%	3.958	-93838.4	1.7349	FALSE	FALSE