Bam-readcount - rapid generation of basepair-resolution sequence metrics

Khanna, Ajay; Larson, David E.; Srivatsan, Sridhar Nonavinkere; Mosior, Matthew; Abbott, Travis E.; Kiwala, Susanna; Ley, Timothy J.; Duncavage, Eric J.; Walter, Matthew J.; Walker, Jason; Griffith, Obi L.; Griffith, Malachi; Miller, Christopher A.

doi:10.21105/joss.03722

Cited by 54 publications

(38 citation statements)

References 18 publications

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“…We applied the SNP-sites tool33 to identify single nucleotide variations (SNVs) based on the MAFFT-alignment of the consensus sequence of case 2 and the reference genome mentioned above. SNVs were checked for sequencing depth and agreement on the sequencing data for the alternative allele using the tool bam-readcount 34.…”

mentioning

confidence: 99%

Retrospective detection of asymptomatic monkeypox virus infections among male sexual health clinic attendees in Belgium

Baetselier

Kenyon²,

Coppens³

et al. 2022

Nat Med

228

176

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The magnitude of the 2022 multi-country monkeypox virus (MPXV) outbreak has surpassed any preceding outbreak. It is unclear whether asymptomatic or otherwise undiagnosed infections are fuelling this epidemic. In this study, we aimed to assess whether undiagnosed infections occurred among men attending a Belgian sexual health clinic in May 2022. We retrospectively screened 224 samples collected for gonorrhea and chlamydia testing using an MPXV PCR assay and identified MPXV-DNA-positive samples from four men. At the time of sampling, one man had a painful rash, and three men had reported no symptoms. Upon clinical examination 21–37 days later, these three men were free of clinical signs, and they reported not having experienced any symptoms. Serology confirmed MPXV exposure in all three men, and MPXV was cultured from two cases. These findings show that certain cases of monkeypox remain undiagnosed and suggest that testing and quarantining of individuals reporting symptoms may not suffice to contain the outbreak.

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mentioning

confidence: 99%

Retrospective detection of asymptomatic monkeypox virus infections among male sexual health clinic attendees in Belgium

Baetselier

Kenyon²,

Coppens³

et al. 2022

Nat Med

228

176

View full text Add to dashboard Cite

show abstract

“…Allele-specific copy number alterations were called using FACETS [17]. Somatic mutations were called using a consensus method to reduce false positives, and bam-readcount [18] was used to compute variant allele frequencies (VAFs). Variants called in at least two of three methods, Mutect2 [16], Lancet [19], and Strelka [20], with at least 10 reads supporting the alternate allele, were retained for further analysis.…”

Section: Whole-exome Sequencingmentioning

confidence: 99%

Triple MAPK inhibition salvaged a relapsed post-BCMA CAR-T cell therapy multiple myeloma patient with a BRAF V600E subclonal mutation

et al. 2022

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Background Multiple Myeloma (MM) is a progressive plasma cell neoplasm characterized by heterogeneous clonal expansion. Despite promising response rates achieved with anti-BCMA CAR-T cell therapy, patients may still relapse and there are currently no clear therapeutic options in post-CAR-T settings. In this report, we present a case of a post-BCMA CAR-T relapsed/refractory (RR) MM patient with skin extramedullary disease (EMD) in which a novel MAPK inhibition combinatorial strategy was implemented based on next-generation sequencing and in vitro experiments. Case presentation A 61-year-old male with penta-refractory MM penta- (IgA lambda), ISS stage 3 with hyperdiploidy, gain of 1q21 and del13 was treated with anti-BCMA CAR-T cell therapy, achieving a best response of VGPR. He progressed after 6 months and was salvaged for a short period with autologous stem cell transplantation. Eventually, he progressed with extramedullary disease manifested as subcutaneous nodules. Based on whole-exome sequencing, we identified a BRAF (V600E) dominant subclone in both bone marrow and cutaneous plasmacytoma. Following in vitro experiments, and according to our previous studies, we implemented a triple MAPK inhibition strategy under which the patient achieved a very good partial response for 110 days, which allowed to bridge him to subsequent clinical trials and eventually achieve a stringent complete response (sCR). Conclusion Here, we show the applicability, effectiveness, and tolerability the triple MAPK inhibition strategy in the context of post-BCMA CAR-T failure in specific subset of patients. The triple therapy could bridge our hospice bound RRMM patient with BRAF (V600E) to further therapeutic options where sCR was achieved. We will further evaluate triple MAPK inhibition in patients with BRAF V600E in a precision medicine clinical trial launching soon.

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“…To filter out the FFPE artefacts, we employed Support Vector Machine-based (SVM) methodology with the e1071 R library. 51 For each sample separately, each variant in the prefiltered VCF file (the same filters as for the fresh non-FFPE samples) was annotated with additional quality information specific for the alternative allele from the BAM file using bam-readcount utility 52 . This additional BAM-derived information in the form of a table was merged with the quality annotations from the VCF file (VCF was parsed into a table with vcf2tsv from vcflib library 53 ) which included CONTQ (Phred-scaled qualities that alt allele are not due to contamination), SEQQ (Phred-scaled quality that alt alleles are not sequencing errors), STRANDQ (Phred-scaled quality of strand bias artifact), TLOD (Log 10 likelihood ratio score of variant existing versus not existing).…”

Section: Methodsmentioning

confidence: 99%

Analysis of Skin Cancers from Xeroderma Pigmentosum Patients Reveals Heterogeneous UV-Induced Mutational Profiles Shaped by DNA Repair

Yurchenko

Rajabi

Braz-Petta

et al. 2022

Preprint

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Xeroderma pigmentosum (XP) is a genetic disorder caused by mutations in genes of the Nucleotide Excision Repair (NER) pathway (groups A-G) or in Translesion Synthesis (TLS) DNA polymerase eta; (V). XP is associated with an increased skin cancer risk, reaching, for some groups, several thousand-fold compared to the general population. Here, we analyzed 38 skin cancer genomes from five XP groups. We found that the activity of NER determines heterogeneity of the mutation rates across skin cancer genomes and that transcription-coupled NER extends beyond the gene boundaries reducing the intergenic mutation rate. Mutational profile in XP-V tumors and experiments with POLH-KO cell line revealed the role of polymerase eta; in the error-free bypass of (i) rare TpG and TpA DNA lesions, (ii) 3' nucleotides in pyrimidine dimers, and (iii) TpT photodimers. Our study unravels the genetic basis of skin cancer risk in XP and provides insights into the mechanisms reducing UV-induced mutagenesis in the general population.

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Bam-readcount - rapid generation of basepair-resolution sequence metrics

Cited by 54 publications

References 18 publications

Retrospective detection of asymptomatic monkeypox virus infections among male sexual health clinic attendees in Belgium

Retrospective detection of asymptomatic monkeypox virus infections among male sexual health clinic attendees in Belgium

Triple MAPK inhibition salvaged a relapsed post-BCMA CAR-T cell therapy multiple myeloma patient with a BRAF V600E subclonal mutation

Analysis of Skin Cancers from Xeroderma Pigmentosum Patients Reveals Heterogeneous UV-Induced Mutational Profiles Shaped by DNA Repair

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