Body: <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>
  
Comments.ContentLicense: CC BY-SA 4.0
Comments.CreationDate: 2024-05-05T18:46:10.823Z
Comments.Text: I have the same problem with a dataset of 10k people. I am wondering did you find a solution on this? Thanks!
Comments.UserDisplayName: R.S.
Comments.ContentLicense: CC BY-SA 4.0
Comments.CreationDate: 2024-05-05T20:26:28.017Z
Comments.Text: Can you tell us more about the "NonSNP site"? Do you know whether that might break something?
Comments.UserDisplayName: Maximilian Press
Comments.ContentLicense: CC BY-SA 4.0
Comments.CreationDate: 2024-05-07T16:27:31.317Z
Comments.Text: @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).
Comments.UserDisplayName: BigMistake
Tags: <vcf><imputation>
Title: How do I fix chromosome-specific Michigan Imputation Server error (Imputation on chromosome 14 failed. Imputation was stopped)
ThreadText: # 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**: @username_2 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
  
  