Collaborating genomic, transcriptomic and microbiomic alterations lead to canine extreme intestinal polyposis

Wang, Jin; Wang, Tianfang; Bishop, Micah A.; Edwards, John F.; Yin, Hang; Dalton, Stephen; Bryan, Laura K.; Zhao, Shaying

doi:10.18632/oncotarget.25646

Cited by 17 publications

(32 citation statements)

References 55 publications

(95 reference statements)

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“…Strain or substrain level variations may also be biologically relevant; for example, a previous study demonstrated that a specific strain of bacteria, Bifidobacterium animalis AHC7, prevents pathogens from colonizing the canine gut [18]. In addition to the differences in bacterial abundance, differences in functional categories can also be important indicators of gut health [8,12,63,69,73]. However, 16S is not useful in resolving taxonomic differences beyond genus level and it has limited utility in assessing functional profiles of the gut microbiome.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to providing strain level information, metagenomic approaches also have the potential to reveal functional differences (e.g., those obtained via KEGG module analysis) that provide a deeper understanding of the functions of the gut microbiome. A handful of studies have already implemented a shotgun metagenomics approach to delineate the role of microbiome in animal health and diseases [8,12,63,69,73]. If deep shotgun sequencing is prohibitively expensive, shallow-depth shotgun sequencing may be alternative to 16S sequencing as it can provide species and/or strain level taxonomic resolution as well as functional data at approximately the same cost as 16S sequencing [96].…”

Section: Discussionmentioning

confidence: 99%

“…microbial medicines, postbiotics) in pets [16,97]. Furthermore, given these pets share a common household environment with humans and have common gut bacteria, a better understanding of pet microbiomes has the potential to illuminate novel links between the microbiome and human diseases [8,12,63,69,[97][98][99][100].…”

Section: Discussionmentioning

confidence: 99%

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Characterization of gut microbiomes of household pets in the United States using a direct-to-consumer approach

Jha¹,

Shmalberg

Tanprasertsuk³

et al. 2020

PLoS ONE

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The role of gut microbiomes as important regulators of mammalian health is increasingly recognized, although feline and canine gut microbiomes remain poorly characterized. In this proof-of-concept study, we assessed the utility of a direct-to-consumer approach to executing pet microbiome studies. We characterized the gut microbiomes of 238 pets (46 cats and 192 dogs) by generating~11 million merged reads that were mapped to the V4 region of 16S ribosomal RNA gene at a sequencing depth of 45,806 (±22,325) reads per sample. Analyses of these reads revealed that both feline and canine gut microbiomes are dominated by three major phyla, namely Firmicutes, Proteobacteria, and Bacteroides and that alpha diversity is higher in the feline gut. In addition to interspecies differences between the feline and canine gut, we also detected appreciable intraspecies bacterial variation within the canine population. While the dogs in this dataset could be assigned to three distinct clusters based on their gut microbiome, no clustering was observed within the feline population. Integration of additional data obtained from survey questionnaires revealed that geography and body weight may be associated with canine gut microbiome composition. Furthermore, we found that both the inter and intraspecies differences are more pronounced at finer taxonomic levels, indicating that strain-level investigations may be necessary in the future. This study demonstrates that the direct-to-consumer approach overcomes existing limitations in pet microbiome research, for example, it allows collection of large numbers of pet samples. The direct-to-consumer approach has proven successful in human genomics as well as human microbiomics and this study demonstrates that by building partnerships with an engaged general public this approach can also propel the field of pet microbiomics forward.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Characterization of gut microbiomes of household pets in the United States using a direct-to-consumer approach

Jha¹,

Shmalberg

Tanprasertsuk³

et al. 2020

PLoS ONE

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“…Spontaneous canine cancers represent one of the best animal models of human cancers [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 ]. Being naturally occurring, heterogeneous and with an intact immune system, they capture the essence of human cancer, unlike most genetically modified or xenograft rodent models.…”

Section: Introductionmentioning

confidence: 99%

Proliferative and Invasive Colorectal Tumors in Pet Dogs Provide Unique Insights into Human Colorectal Cancer

Wang

Sun

et al. 2018

Cancers

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Spontaneous tumors in pet dogs represent a valuable but undercharacterized cancer model. To better use this resource, we performed an initial global comparison between proliferative and invasive colorectal tumors from 20 canine cases, and evaluated their molecular homology to human colorectal cancer (CRC). First, proliferative canine tumors harbor overactivated WNT/β-catenin pathways and recurrent CTNNB1 (β-catenin) mutations S45F/P, D32Y and G34E. Invasive canine tumors harbor prominent fibroblast proliferation and overactivated stroma. Both groups have recurrent TP53 mutations. We observed three invasion patterns in canine tumors: collective, crypt-like and epithelial–mesenchymal transition (EMT). We detected enriched Helicobacter bilis and Alistipes finegoldii in proliferative and crypt-like tumors, but depleted mucosa-microbes in the EMT tumor. Second, guided by our canine findings, we classified 79% of 478 human colon cancers from The Cancer Genome Atlas into four subtypes: primarily proliferative, or with collective, crypt-like or EMT invasion features. Their molecular characteristics match those of canine tumors. We showed that consensus molecular subtype 4 (mesenchymal) of human CRC should be further divided into EMT and crypt-like subtypes, which differ in TGF-β activation and mucosa-microbe content. Our canine tumors share the same pathogenic pathway as human CRCs. Dog-human integration identifies three CRC invasion patterns and improves CRC subtyping.

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“…We applied our KPR assembler ( Figure 1) to our canine RNA-seq data, 27 to 87 million pairedend reads of 76x76bp or 50x50bp each of dogs with various cancers 19,[26][27][28] . We then performed Sanger sequencing on 13 samples to validate the assembled contigs.…”

Section: Contigs Assembled By Our Tools Are Validated By Sanger Sequementioning

confidence: 99%

A Kmer-based paired-end read (KPR) de novo assembler and genotyper to genotype major histocompatibility complex class I (MHC-I) alleles for the dog

Yuan

Hildebrand

Tompkins

et al. 2020

Preprint

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The major histocompatibility complex class I (MHC-I) genes are highly polymorphic among individuals. MHC-I genotyping is required for determining the antigen-binding specificity of each MHC-I molecule in an individual. Numerous tools have been developed for human MHC-I genotyping using deep sequencing data such as RNA-seq; however they do not work for the dog, due to very limited known canine alleles. To address this issue, we developed a Kmer-based paired-end read (KPR) de novo assembler and genotyper, which first assemble paired-end RNA-seq reads mapped to the MHC-I regions into contigs de novo and then genotype each contig. Our KPR tools are validated by Sanger sequencing, simulation and published genotype data. Applying our KPR tools on the published RNA-seq data of 158 tumor and 64 normal samples from 158 dogs, we have achieved a genotyping success rate of 86%, which includes 133 tumor and 57 normal samples from 142 dogs. We have identified 39 known alleles and 83 new alleles of high confidence in these dogs, yielding a more comprehensive MHC-I allele diversity landscape for the dog.

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Collaborating genomic, transcriptomic and microbiomic alterations lead to canine extreme intestinal polyposis

Cited by 17 publications

References 55 publications

Characterization of gut microbiomes of household pets in the United States using a direct-to-consumer approach

Characterization of gut microbiomes of household pets in the United States using a direct-to-consumer approach

Proliferative and Invasive Colorectal Tumors in Pet Dogs Provide Unique Insights into Human Colorectal Cancer

A Kmer-based paired-end read (KPR) de novo assembler and genotyper to genotype major histocompatibility complex class I (MHC-I) alleles for the dog

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