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Tataru, C.

Publications and source records attributed to Tataru, C..

3 recordsLinked to original sources

Learning a deep language model for microbiomes: the power of large scale unlabeled microbiome data

We use open source human gut microbiome data to learn a microbial "language" model by adapting techniques from Natural Language Processing (NLP). Our microbial "language" model is trained in a self-supervised fashion (i.e., without additional external labels) to capture the interactions among different microbial taxa and the common compositional patterns in microbial communities. The learned model produces contextualized taxa representations that allow a single microbial taxon to be represented differently according to the specific microbial environment it appears in. The model further provides a sample representation by collectively interpreting different microbial taxa in the sample and their interactions as a whole. We show that, compared to baseline representations, our sample representation consistently leads to improved performance for multiple prediction tasks including predicting Irritable Bowel Disease (IBD) and diet patterns. Coupled with a simple ensemble strategy, it produces a highly robust IBD prediction model that generalizes well to microbiome data independently collected from different populations with substantial distribution shift. We visualize the contextualized taxa representations and find that they exhibit meaningful phylum-level structure, despite never exposing the model to such a signal. Finally, we apply an interpretation method to highlight microbial taxa that are particularly influential in driving our models predictions for IBD. Author summaryHuman microbiomes and their interactions with various body systems have been linked to a wide range of diseases and lifestyle variables. To understand these links, citizen science projects such as the American Gut Project (AGP) have provided large open-source datasets for microbiome investigation. In this work we leverage such open-source data and learn a "language" model for human gut microbiomes using techniques derived from natural language processing. We train the "language" model to capture the interactions among different microbial taxa and the common compositional patterns that shape gut microbiome communities. By considering the entirety of taxa within a sample and their interactions, our model produces a representation that enables contextualized interpretation of individual microbial taxa within their microbial environment. We demonstrate that our sample representation enhances prediction performance compared to baseline methods across multiple microbiome tasks including prediction of Irritable Bowel Disease (IBD) and diet patterns. Furthermore, our learned representation yields a robust IBD prediction model that generalizes well to independent data collected from different populations. To gain insight into our models workings, we present interpretation results that showcase its ability to learn biologically meaningful representations.

microbiology↗

Topic modeling for multi-omic integration in the human gut microbiome and implications for autism

While healthy gut microbiomes are critical to human health, pertinent microbial processes remain largely undefined, partially due to differential bias among profiling techniques. By simultaneously integrating multiple profiling methods, multi-omic analysis can define generalizable microbial pro-cesses, and is especially useful in understanding complex conditions such as Autism. Challenges with integrating heterogeneous data produced by multiple profiling methods can be overcome using Latent Dirichlet Allocation (LDA), a promising natural language processing technique that identifies topics in heterogeneous documents. In this study, we apply LDA to multi-omic microbial data (16S rRNA amplicon, shotgun metagenomic, shotgun metatranscriptomic, and untargeted metabolomic profiling) from the stool of 81 children with and without Autism. We identify topics, or microbial processes, that summarize complex phenomena occurring within gut microbial communities. We then subset stool samples by topic distribution, and identify metabolites, specifically neurotransmitter precursors and fatty acid derivatives, that differ significantly between children with and without Autism. We identify clusters of topics, deemed "cross-omic topics", which we hypothesize are representative of generalizable microbial processes observable regardless of profiling method. Interpreting topics, we find each represents a particular diet, and we heuristically label each cross-omic topic as: healthy/general function, age-associated function, transcriptional regulation, and opportunistic pathogenesis.

bioinformatics↗

Crowdsourced study of children with autism and their typically developing siblings identifies differences in taxonomic and predicted function for stool-associated microbes using exact sequence variant analysis.

BackgroundThe existence of a link between the gut microbiome and autism spectrum disorder (ASD) is well established in mice, but in human populations efforts to identify microbial biomarkers have been limited due to problems stratifying participants within the broad phenotype of ASD and a lack of appropriately matched controls. To overcome these limitations and investigate the relationship between ASD and the gut microbiome, we ran a crowdsourced study of families 2-7 year old sibling pairs, where one child of the pair had a diagnosis of ASD and the other child did not.\n\nMethodsParents of age-matched sibling pairs electronically consented and completed study procedures via a secure web portal (microbiome.stanford.edu). Parents collected stool samples from each child, responded to behavioral questionnaires about the ASD childs typical behavior, and whenever possible provided a home video of their ASD childs natural social behavior. We performed DNA extraction and 16S rRNA amplicon sequencing on 117 stool samples (60 ASD and 57 NT) that met all study design eligibility criteria. Using DADA2, Exact Sequence Variants (ESVs) were identified as taxonomic units, and three statistical tests were performed on ESV abundance counts: (1) permutation test to determine differences between sibling pairs, (2) differential abundance test using a zero-inflated gaussian mixture model to account for the sparse abundance matrix, and (3) differential abundance test after modeling under a negative binomial distribution. The potential functional gene abundance for each sample was also inferred from the 16S rRNA data, providing KEGG Ortholog (KO), which were analyzed for differential abundance.\n\nResultsIn total, 21 ESVs had significantly differentially proportions in stool of children with ASD and their neurotypical siblings. Of these 21 ESVs, 11 were enriched in neurotypical children and ten were enriched in children with ASD. ESVs enriched in the ASD cohort were predominantly associated with Ruminococcaceae and Bacteroidaceae; while those enriched in controls were more diverse including taxa associated with Bifidobacterium, Porphyromonas, Slackia, Desulfovibrio, Acinetobacter johnsonii, and Lachnospiraceae. Exact Variant Analysis suggested that Lachnospiraceae was specific to the control cohort, while Ruminococcaceae, Tissierellaceae and Bacteroidaceae were significantly enriched in children with ASD. Metabolic gene predictions determined that while both cohorts harbor the butyrogenic pathway, the ASD cohort was more likely to use the 4-aminobutanoate (4Ab) pathway, while the control cohort was more likely to use the pyruvate pathway. The 4Ab pathway releases harmful by-products like ammonia and can shunt glutamate, affecting its availability as an excitatory neurotransmitter. Finally, we observed differences in the carbohydrate uptake capabilities of various ESVs identified between the two cohorts.

microbiology↗