Samuel Lancaster

All Publications

• Multi-omics approaches in psychoneuroimmunology and health research: Conceptual considerations and methodological recommendations. Brain, behavior, and immunity Mengelkoch, S., Lautman, Z., Alley, J. C., Roos, L. G., Ehlert, B., Moriarity, D. P., Lancaster, S., Miryam Schussler-Fiorenza Rose, S., Snyder, M. P., Slavich, G. M. 2023

  Abstract

  The field of psychoneuroimmunology (PNI) has grown substantially in both relevance and prominence over the past 40 years. Notwithstanding its impressive trajectory, a majority of PNI studies are still based on a relatively small number of analytes. To advance this work, we suggest that PNI, and health research in general, can benefit greatly from adopting a multi-omics approach, which involves integrating data across multiple biological levels (e.g., the genome, proteome, transcriptome, metabolome, lipidome, and microbiome/metagenome) to more comprehensively profile biological functions and relate these profiles to clinical and behavioral outcomes. To assist investigators in this endeavor, we provide an overview of multi-omics research, highlight recent landmark multi-omics studies investigating human health and disease risk, and discuss how multi-omics can be applied to better elucidate links between psychological, nervous system, and immune system activity. In doing so, we describe how to design high-quality multi-omics PNI studies, decide which biological samples (e.g., blood, stool, urine, saliva, solid tissue) are most relevant, incorporate behavioral and wearable sensing data into multi-omics research, and understand key data quality, integration, analysis, and interpretation issues. PNI researchers are addressing some of the most interesting and important questions at the intersection of psychology, neuroscience, and immunology. Applying a multi-omics approach to this work will greatly expand the horizon of what is possible in PNI and has the potential to revolutionize our understanding of mind-body medicine.

  View details for DOI 10.1016/j.bbi.2023.07.022

  View details for PubMedID 37543247

• Advances and prospects for the Human BioMolecular Atlas Program (HuBMAP). Nature cell biology Jain, S., Pei, L., Spraggins, J. M., Angelo, M., Carson, J. P., Gehlenborg, N., Ginty, F., Gonçalves, J. P., Hagood, J. S., Hickey, J. W., Kelleher, N. L., Laurent, L. C., Lin, S., Lin, Y., Liu, H., Naba, A., Nakayasu, E. S., Qian, W. J., Radtke, A., Robson, P., Stockwell, B. R., Van de Plas, R., Vlachos, I. S., Zhou, M., Börner, K., Snyder, M. P. 2023

  Abstract

  The Human BioMolecular Atlas Program (HuBMAP) aims to create a multi-scale spatial atlas of the healthy human body at single-cell resolution by applying advanced technologies and disseminating resources to the community. As the HuBMAP moves past its first phase, creating ontologies, protocols and pipelines, this Perspective introduces the production phase: the generation of reference spatial maps of functional tissue units across many organs from diverse populations and the creation of mapping tools and infrastructure to advance biomedical research.

  View details for DOI 10.1038/s41556-023-01194-w

  View details for PubMedID 37468756

  View details for PubMedCentralID 8238499

• Global, distinctive, and personal changes in molecular and microbial profiles by specific fibers in humans. Cell host & microbe Lancaster, S. M., Lee-McMullen, B., Abbott, C. W., Quijada, J. V., Hornburg, D., Park, H., Perelman, D., Peterson, D. J., Tang, M., Robinson, A., Ahadi, S., Contrepois, K., Hung, C., Ashland, M., McLaughlin, T., Boonyanit, A., Horning, A., Sonnenburg, J. L., Snyder, M. P. 2022

  Abstract

  Dietary fibers act through the microbiome to improve cardiovascular health and prevent metabolic disorders and cancer. To understand the health benefits of dietary fiber supplementation, we investigated two popular purified fibers, arabinoxylan (AX) and long-chain inulin (LCI), and a mixture of five fibers. We present multiomic signatures of metabolomics, lipidomics, proteomics, metagenomics, a cytokine panel, and clinical measurements on healthy and insulin-resistant participants. Each fiber is associated with fiber-dependent biochemical and microbial responses. AX consumption associates with a significant reduction in LDL and an increase in bile acids, contributing to its observed cholesterol reduction. LCI is associated with an increase in Bifidobacterium. However, at the highest LCI dose, there is increased inflammation and elevation in the liver enzyme alanine aminotransferase. This study yields insights into the effects of fiber supplementation and the mechanisms behind fiber-induced cholesterol reduction, and it shows effects of individual, purified fibers on the microbiome.

  View details for DOI 10.1016/j.chom.2022.03.036

  View details for PubMedID 35483363

• Longitudinal linked-read sequencing reveals ecological and evolutionary responses of a human gut microbiome during antibiotic treatment. Genome research Roodgar, M., Good, B. H., Garud, N. R., Martis, S., Avula, M., Zhou, W., Lancaster, S. M., Lee, H., Babveyh, A., Nesamoney, S., Pollard, K. S., Snyder, M. P. 2021

  Abstract

  Gut microbial communities can respond to antibiotic perturbations by rapidly altering their taxonomic and functional composition. However, little is known about the strain-level processes that drive this collective response. Here, we characterize the gut microbiome of a single individual at high temporal and genetic resolution through a period of health, disease, antibiotic treatment, and recovery. We used deep, linked-read metagenomic sequencing to track the longitudinal trajectories of thousands of single nucleotide variants within 36 species, which allowed us to contrast these genetic dynamics with the ecological fluctuations at the species level. We found that antibiotics can drive rapid shifts in the genetic composition of individual species, often involving incomplete genome-wide sweeps of pre-existing variants. These genetic changes were frequently observed in species without obvious changes in species abundance, emphasizing the importance of monitoring diversity below the species level. We also found that many sweeping variants quickly reverted to their baseline levels once antibiotic treatment had concluded, demonstrating that the ecological resilience of the microbiota can sometimes extend all the way down to the genetic level. Our results provide new insights into the population genetic forces that shape individual microbiomes on therapeutically relevant timescales, with potential implications for personalized health and disease.

  View details for DOI 10.1101/gr.265058.120

  View details for PubMedID 34301627

• A Customizable Analysis Flow in Integrative Multi-Omics. Biomolecules Lancaster, S. M., Sanghi, A., Wu, S., Snyder, M. P. 2020; 10 (12)

  Abstract

  The number of researchers using multi-omics is growing. Though still expensive, every year it is cheaper to perform multi-omic studies, often exponentially so. In addition to its increasing accessibility, multi-omics reveals a view of systems biology to an unprecedented depth. Thus, multi-omics can be used to answer a broad range of biological questions in finer resolution than previous methods. We used six omic measurements-four nucleic acid (i.e., genomic, epigenomic, transcriptomics, and metagenomic) and two mass spectrometry (proteomics and metabolomics) based-to highlight an analysis workflow on this type of data, which is often vast. This workflow is not exhaustive of all the omic measurements or analysis methods, but it will provide an experienced or even a novice multi-omic researcher with the tools necessary to analyze their data. This review begins with analyzing a single ome and study design, and then synthesizes best practices in data integration techniques that include machine learning. Furthermore, we delineate methods to validate findings from multi-omic integration. Ultimately, multi-omic integration offers a window into the complexity of molecular interactions and a comprehensive view of systems biology.

  View details for DOI 10.3390/biom10121606

  View details for PubMedID 33260881

• Fitness benefits of loss of heterozygosity in Saccharomyces hybrids GENOME RESEARCH Lancaster, S. M., Payen, C., Heil, C., Dunham, M. J. 2019; 29 (10): 1685–92

  Abstract

  With two genomes in the same organism, interspecific hybrids have unique fitness opportunities and costs. In both plants and yeasts, wild, pathogenic, and domesticated hybrids may eliminate portions of one parental genome, a phenomenon known as loss of heterozygosity (LOH). Laboratory evolution of hybrid yeast recapitulates these results, with LOH occurring in just a few hundred generations of propagation. In this study, we systematically looked for alleles that are beneficial when lost in order to determine how prevalent this mode of adaptation may be and to determine candidate loci that might underlie the benefits of larger-scale chromosome rearrangements. These aims were accomplished by mating Saccharomyces uvarum with the S. cerevisiae deletion collection to create hybrids such that each nonessential S. cerevisiae allele is deleted. Competitive fitness assays of these pooled, barcoded, hemizygous strains, and accompanying controls, revealed a large number of loci for which LOH is beneficial. We found that the fitness effects of hemizygosity are dependent on the species context, the selective environment, and the species origin of the deleted allele. Further, we found that hybrids have a wider distribution of fitness consequences versus matched S. cerevisiae hemizygous diploids. Our results suggest that LOH can be a successful strategy for adaptation of hybrids to new environments, and we identify candidate loci that drive the chromosomal rearrangements observed in evolution of yeast hybrids.

  View details for DOI 10.1101/gr.245605.118

  View details for Web of Science ID 000488528500010

  View details for PubMedID 31548357