Evidence map›Paper›PMID 29304755›Full record

ArticleBMC genomics2018

Computational approach to discriminate human and mouse sequences in patient-derived tumour xenografts.

Maurizio Callari, Ankita Sati Batra, Rajbir Nath Batra, Stephen-John Sammut, Wendy Greenwood, Harry Clifford, Colin Hercus, Suet-Feung Chin, Alejandra Bruna, Oscar M Rueda and 1 more

Abstract readEvaluation Study
In one paragraph

Article in BMC genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

40 citing papers in PubMed.

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  12. Review
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  16. RNA-Seq Data Processing in Plant-Pathogen Interaction System: A Case Study.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  17. Article
  18. Article
  19. Article
  20. Tumor Purity in Preclinical Mouse Tumor Models.Cancer research communications · 2022
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Maurizio CallariCRUK Cambridge Institute and Department of Oncology, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Ankita Sati BatraCRUK Cambridge Institute and Department of Oncology, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Rajbir Nath BatraCRUK Cambridge Institute and Department of Oncology, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Stephen-John SammutCRUK Cambridge Institute and Department of Oncology, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Wendy GreenwoodCRUK Cambridge Institute and Department of Oncology, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Harry CliffordCRUK Cambridge Institute and Department of Oncology, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Colin HercusNovocraft Technologies Sdn Bhd, C-23A-05, 3 Two Square, Jalan 19/1, Section 19, 46300, Petaling Jaya, Selangor Darul Ehsan, Malaysia.
Suet-Feung ChinCRUK Cambridge Institute and Department of Oncology, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Alejandra BrunaCRUK Cambridge Institute and Department of Oncology, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Oscar M RuedaCRUK Cambridge Institute and Department of Oncology, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.
Carlos CaldasCRUK Cambridge Institute and Department of Oncology, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK. carlos.caldas@cruk.cam.ac.uk.

Funding

Cancer Research UK 16942
6 · The paper itself

Abstract

backgroundPatient-Derived Tumour Xenografts (PDTXs) have emerged as the pre-clinical models that best represent clinical tumour diversity and intra-tumour heterogeneity. The molecular characterization of PDTXs using High-Throughput Sequencing (HTS) is essential; however, the presence of mouse stroma is challenging for HTS data analysis. Indeed, the high homology between the two genomes results in a proportion of mouse reads being mapped as human.

resultsIn this study we generated Whole Exome Sequencing (WES), Reduced Representation Bisulfite Sequencing (RRBS) and RNA sequencing (RNA-seq) data from samples with known mixtures of mouse and human DNA or RNA and from a cohort of human breast cancers and their derived PDTXs. We show that using an In silico Combined human-mouse Reference Genome (ICRG) for alignment discriminates between human and mouse reads with up to 99.9% accuracy and decreases the number of false positive somatic mutations caused by misalignment by >99.9%. We also derived a model to estimate the human DNA content in independent PDTX samples. For RNA-seq and RRBS data analysis, the use of the ICRG allows dissecting computationally the transcriptome and methylome of human tumour cells and mouse stroma. In a direct comparison with previously reported approaches, our method showed similar or higher accuracy while requiring significantly less computing time.

conclusionsThe computational pipeline we describe here is a valuable tool for the molecular analysis of PDTXs as well as any other mixture of DNA or RNA species.

Indexed as

Xenograft Model Antitumor AssaysAnimalsBreast NeoplasmsGene Expression ProfilingGenomicsHigh-Throughput Nucleotide SequencingHumansMiceMutationSequence AlignmentSequence Analysis, DNASequence Analysis, RNAAlignmentHigh throughput sequencingICRGIn silico combined human-mouse reference genomeMouse stromaPatient-derived tumour xenograftsShort-reads

Identifiers

PMID29304755
PMCPMC5755132

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.