<p>I am imputing human genome samples, all hg19, using the Michigan Imputation Server. The input of the data is one VCF per autosome, which each VCF containing a few dozen samples.</p>
<p>The samples within the VCF are from highly heterogenous sources (various genotype arrays, from multiple labs). I have cleaned and standardized the data (removed indels, multiallelic sites, duplicates, and non-standard genotypes). I merged the samples into a single file for each chromosome. The VCF may not be left-aligned.</p>
<p>It passes all QC with no issues, and then fails and gives no error message beyond &quot;unfortunately, your job failed&quot; and &quot;Imputation on chromosome 14 failed. Imputation was stopped.&quot;</p>
<p>As a test, I imputed chromosome 1, chromosome 13, and chromosome 14  by themselves. Chromosome 1 and 13 worked perfectly, but chromosome 14 failed imputation. I have no idea why chromosome 14 would be special or different. Also, imputing chromosomes 1-13 failed on chromosome 9, so it appears only certain chromosomes are causing issues.</p>
<p>Does anyone have ideas as to why this might be occurring, or how to fix this issue?</p>
<p>I dislike using hg19. I am using that because that is the build that some of the genome data I received is on. Labs are still using hg19 in the present day, for some reason. However, I have used hg19 successfully on the Michigan Imputation Server before, and it supports both hg19 and hg38, so I don't think build is the issue. I have a different batch of hg38 data that I will run through the server later.</p>
<p>Here is a comparison between the QC statistics:</p>
<div class="s-table-container">
<table class="s-table">
<thead>
<tr>
<th>Chromosome:</th>
<th>13 (success)</th>
<th>14 (failure)</th>
</tr>
</thead>
<tbody>
<tr>
<td>SNPs</td>
<td>75,675</td>
<td>69,049</td>
</tr>
<tr>
<td>Chunks</td>
<td>6</td>
<td>6</td>
</tr>
<tr>
<td>Datatype</td>
<td>unphased</td>
<td>unphased</td>
</tr>
<tr>
<td>Build</td>
<td>hg19</td>
<td>hg19</td>
</tr>
<tr>
<td>Reference Panel</td>
<td>apps@1000g-phase-3-v5 (hg19)</td>
<td>apps@1000g-phase-3-v5 (hg19)</td>
</tr>
<tr>
<td>Alternative allele frequency</td>
<td>&gt; 0.5 sites: 14,015</td>
<td>&gt; 0.5 sites: 11,776</td>
</tr>
<tr>
<td>Reference Overlap</td>
<td>99.18%</td>
<td>99.25%</td>
</tr>
<tr>
<td>Match</td>
<td>44,261</td>
<td>39,947</td>
</tr>
<tr>
<td>Allele switch</td>
<td>0</td>
<td>0</td>
</tr>
<tr>
<td>Strand flip</td>
<td>0</td>
<td>0</td>
</tr>
<tr>
<td>Strand flip and allele switch</td>
<td>0</td>
<td>0</td>
</tr>
<tr>
<td>A/T, C/G genotypes</td>
<td>0</td>
<td>0</td>
</tr>
<tr>
<td>Filter flag set</td>
<td>367</td>
<td>342</td>
</tr>
<tr>
<td>Invalid alleles</td>
<td>20,567</td>
<td>18,022</td>
</tr>
<tr>
<td>Multiallelic sites</td>
<td>12</td>
<td>16</td>
</tr>
<tr>
<td>Duplicated sites</td>
<td>0</td>
<td>0</td>
</tr>
<tr>
<td>NonSNP sites</td>
<td>0</td>
<td>0</td>
</tr>
<tr>
<td>Monomorphic sites</td>
<td>9,963</td>
<td>10,302</td>
</tr>
<tr>
<td>Allele mismatch</td>
<td>138</td>
<td>116</td>
</tr>
<tr>
<td>SNPs call rate &lt; 90%</td>
<td>43,096</td>
<td>38,760</td>
</tr>
<tr>
<td>Excluded sites in total</td>
<td>74,143</td>
<td>67,558</td>
</tr>
<tr>
<td>Remaining sites in total</td>
<td>1,165</td>
<td>1,187</td>
</tr>
<tr>
<td>Typed only sites</td>
<td>367</td>
<td>304</td>
</tr>
<tr>
<td>Execution status</td>
<td>successful</td>
<td>successful</td>
</tr>
</tbody>
</table>
</div>
<p>Per the Michigan Imputation Server documentation, I've checked my input VCF files with CheckVCF.</p>
<p>Here are the results on the chromosome VCF file that failed:</p>
<pre><code>---------------     REPORT     ---------------
Total [ 69095 ] lines processed
Examine [ 49 ] VCF header lines, [ 69046 ] variant sites, [ 21 ] samples
[ 0 ] duplicated sites
[ 0 ] NonSNP site are outputted to [ test.check.nonSnp ]
[ 0 ] Inconsistent reference sites are outputted to [ test.check.ref ]
[ 0 ] Variant sites with invalid genotypes are outputted to [ test.check.geno ]
[ 11947 ] Alternative allele frequency &gt; 0.5 sites are outputted to [ test.check.af ]
[ 34408 ] Monomorphic sites are outputted to [ test.check.mono ]
---------------     ACTION ITEM     ---------------
* No error found by checkVCF.py, thank you for cleanning VCF file.
</code></pre>
<p>Here are the results on the chromosome VCF file that succeeded:</p>
<pre><code>---------------     REPORT     ---------------
Total [ 75718 ] lines processed
Examine [ 49 ] VCF header lines, [ 75669 ] variant sites, [ 21 ] samples
[ 0 ] duplicated sites
[ 1 ] NonSNP site are outputted to [ test.check.nonSnp ]
[ 0 ] Inconsistent reference sites are outputted to [ test.check.ref ]
[ 0 ] Variant sites with invalid genotypes are outputted to [ test.check.geno ]
[ 14059 ] Alternative allele frequency &gt; 0.5 sites are outputted to [ test.check.af ]
[ 37553 ] Monomorphic sites are outputted to [ test.check.mono ]
---------------     ACTION ITEM     ---------------
* No error found by checkVCF.py, thank you for cleanning VCF file.
</code></pre>

CC BY-SA 4.0
2024-05-05T18:46:10.823Z
I have the same problem with a dataset of 10k people. I am wondering did you find a solution on this? Thanks!
R.S.
CC BY-SA 4.0
2024-05-05T20:26:28.017Z
Can you tell us more about the "NonSNP site"? Do you know whether that might break something?
Maximilian Press
CC BY-SA 4.0
2024-05-07T16:27:31.317Z
@MaximilianPress Good thought; I see that difference. I don't remember what that was, but I ended up just not using the MIS (buggy for various other reasons / poor documentation).
BigMistake
<vcf><imputation>
How do I fix chromosome-specific Michigan Imputation Server error (Imputation on chromosome 14 failed. Imputation was stopped)
# How do I fix chromosome-specific Michigan Imputation Server error (Imputation on chromosome 14 failed. Imputation was stopped)

(Asked by: username_0 on 2023-06-14)

I am imputing human genome samples, all hg19, using the Michigan Imputation Server. The input of the data is one VCF per autosome, which each VCF containing a few dozen samples.
The samples within the VCF are from highly heterogenous sources (various genotype arrays, from multiple labs). I have cleaned and standardized the data (removed indels, multiallelic sites, duplicates, and non-standard genotypes). I merged the samples into a single file for each chromosome. The VCF may not be left-aligned.
It passes all QC with no issues, and then fails and gives no error message beyond "unfortunately, your job failed" and "Imputation on chromosome 14 failed. Imputation was stopped."
As a test, I imputed chromosome 1, chromosome 13, and chromosome 14  by themselves. Chromosome 1 and 13 worked perfectly, but chromosome 14 failed imputation. I have no idea why chromosome 14 would be special or different. Also, imputing chromosomes 1-13 failed on chromosome 9, so it appears only certain chromosomes are causing issues.
Does anyone have ideas as to why this might be occurring, or how to fix this issue?
I dislike using hg19. I am using that because that is the build that some of the genome data I received is on. Labs are still using hg19 in the present day, for some reason. However, I have used hg19 successfully on the Michigan Imputation Server before, and it supports both hg19 and hg38, so I don't think build is the issue. I have a different batch of hg38 data that I will run through the server later.
Here is a comparison between the QC statistics:




Chromosome:
13 (success)
14 (failure)




SNPs
75,675
69,049


Chunks
6
6


Datatype
unphased
unphased


Build
hg19
hg19


Reference Panel
apps@1000g-phase-3-v5 (hg19)
apps@1000g-phase-3-v5 (hg19)


Alternative allele frequency
> 0.5 sites: 14,015
> 0.5 sites: 11,776


Reference Overlap
99.18%
99.25%


Match
44,261
39,947


Allele switch
0
0


Strand flip
0
0


Strand flip and allele switch
0
0


A/T, C/G genotypes
0
0


Filter flag set
367
342


Invalid alleles
20,567
18,022


Multiallelic sites
12
16


Duplicated sites
0
0


NonSNP sites
0
0


Monomorphic sites
9,963
10,302


Allele mismatch
138
116


SNPs call rate < 90%
43,096
38,760


Excluded sites in total
74,143
67,558


Remaining sites in total
1,165
1,187


Typed only sites
367
304


Execution status
successful
successful




Per the Michigan Imputation Server documentation, I've checked my input VCF files with CheckVCF.
Here are the results on the chromosome VCF file that failed:
---------------     REPORT     ---------------
Total [ 69095 ] lines processed
Examine [ 49 ] VCF header lines, [ 69046 ] variant sites, [ 21 ] samples
[ 0 ] duplicated sites
[ 0 ] NonSNP site are outputted to [ test.check.nonSnp ]
[ 0 ] Inconsistent reference sites are outputted to [ test.check.ref ]
[ 0 ] Variant sites with invalid genotypes are outputted to [ test.check.geno ]
[ 11947 ] Alternative allele frequency > 0.5 sites are outputted to [ test.check.af ]
[ 34408 ] Monomorphic sites are outputted to [ test.check.mono ]
---------------     ACTION ITEM     ---------------
* No error found by checkVCF.py, thank you for cleanning VCF file.

Here are the results on the chromosome VCF file that succeeded:
---------------     REPORT     ---------------
Total [ 75718 ] lines processed
Examine [ 49 ] VCF header lines, [ 75669 ] variant sites, [ 21 ] samples
[ 0 ] duplicated sites
[ 1 ] NonSNP site are outputted to [ test.check.nonSnp ]
[ 0 ] Inconsistent reference sites are outputted to [ test.check.ref ]
[ 0 ] Variant sites with invalid genotypes are outputted to [ test.check.geno ]
[ 14059 ] Alternative allele frequency > 0.5 sites are outputted to [ test.check.af ]
[ 37553 ] Monomorphic sites are outputted to [ test.check.mono ]
---------------     ACTION ITEM     ---------------
* No error found by checkVCF.py, thank you for cleanning VCF file.

**Tags:** vcf, imputation
> **Comments:**
> **username_1**: I have the same problem with a dataset of 10k people. I am wondering did you find a solution on this? Thanks!  
> **username_2**: Can you tell us more about the "NonSNP site"? Do you know whether that might break something?  
> **username_0**: @MaximilianPress Good thought; I see that difference. I don't remember what that was, but I ended up just not using the MIS (buggy for various other reasons / poor documentation).  

---

## 0 answers

