Brian DeFelice

• University of California, Davis

The long-term success of introduced populations depends on both their initial size and ability to compete against existing residents, but it remains unclear how these factors collectively shape colonization dynamics. Here, we investigate how initial population (propagule) size shapes the outcome of community coalescence by systematically mixing eig...

Consistently collecting high-quality liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS) data is a time-consuming hurdle for untargeted workflows. Analytical controls such as internal and biological standards are commonly included in high-throughput workflows, helping researchers recognize low-integrity specimens regardless of their b...

Background Early detection of the cell type changes underlying several genitourinary tract diseases largely remains an unmet clinical need, where existing assays, if available, lack the cellular resolution afforded by an invasive biopsy. While messenger RNA in urine could reflect the dynamic signal that facilitates early detection, current measurem...

Human gut commensal bacteria are routinely exposed to various stresses, including therapeutic drugs, and collateral effects are difficult to predict. To systematically interrogate community-level effects of drug perturbations, we screened stool-derived in vitro communities with 707 clinically relevant small molecules. Across ∼5,000 community–drug i...

Microbial community dynamics arise through interspecies interactions, including resource competition, cross-feeding and pH modulation. The individual contributions of these mechanisms to community structure are challenging to untangle. Here we develop a framework to estimate multispecies niche overlaps by combining metabolomics data of individual s...

Gut bacteria rapidly evolve in vivo , but their long-term success requires dispersal across hosts. Here, we quantify this interplay by tracking >50,000 genomically barcoded lineages of the prevalent commensal Bacteroides thetaiotaomicron ( Bt ) among co-housed mice. We find that adaptive mutations rapidly spread between hosts, overcoming the natura...

Urine is assayed alongside blood in medicine, yet current clinical diagnostic tests utilize only a small fraction of its total biomolecular repertoire, potentially foregoing high-resolution insights into human health and disease. In this work, we characterized the joint landscapes of transcriptomic and metabolomic signals in human urine. We also co...

Bifidobacteria commonly represent a dominant constituent of human gut microbiomes during infancy, influencing nutrition, immune development, and resistance to infection. Despite interest as a probiotic therapy, predicting the nutritional requirements and health-promoting effects of Bifidobacteria is challenging due to major knowledge gaps. To overc...

Human gut bacteria perform diverse metabolic functions with consequences for host health. The prevalent and disease-linked Actinobacterium Eggerthella lenta performs several unusual chemical transformations, but it does not metabolize sugars and its core growth strategy remains unclear. To obtain a comprehensive view of the metabolic network of E....

Nutrient availability fluctuates in most natural populations, forcing organisms to undergo periods of fasting and re-feeding. It is unknown how dietary changes influence liver homeostasis. Here, we show that a switch from ad libitum feeding to intermittent fasting (IF) promotes rapid hepatocyte proliferation. Mechanistically, IF-induced hepatocyte...

Both viruses and bacteria produce “pathogen associated molecular patterns” that may affect microbial pathogenesis and anti-microbial responses. Additionally, bacteria produce metabolites, while viruses could change the metabolic profiles of the infected cells. Here, we used an unbiased metabolomics approach to profile metabolites in spleens and blo...

Both viruses and bacteria produce pathogen associated molecular patterns that may affect microbial pathogenesis and anti-microbial responses. Additionally, bacteria produce metabolites while viruses could change metabolic profiles of the infected cells. Here, we used an unbiased metabolomics approach to profile metabolites in spleens and blood of M...

Human gut bacteria perform diverse metabolic functions with consequences for host health. The prevalent and disease-linked Actinobacterium Eggerthella lenta performs several unusual chemical transformations, but it does not metabolize sugars and its core growth strategy remains unclear. To obtain a comprehensive view of the metabolic network of E....

Lower blood 25 (OH) D concentration is associated with increased risk of islet autoimmunity (IA) in some cohorts; it is not known if 25 (OH) D metabolites are important after the onset of IA. We investigated novel vitamin D metabolites in development of IA and progression from IA to T1D in the Diabetes Autoimmunity Study in the Young (DAISY) . IA w...

Members of microbial communities interact via a plethora of mechanisms, including resource competition, cross-feeding, and pH modulation. However, the relative contributions of these mechanisms to community dynamics remain uncharacterized. Here, we develop a framework to distinguish the effects of resource competition from other interaction mechani...

Objective: Comprehensive assessment of alterations in lipid species preceding type 2 diabetes (T2D) is largely unknown. We aimed to identify plasma molecular lipids associated with risk of T2D in American Indians. Research design and methods: Using untargeted liquid chromatography-mass spectrometry, we repeatedly measured 3,907 fasting plasma sa...

Environmental factors including viruses, diet, and the metabolome have been linked with the appearance of islet autoimmunity (IA) that precedes development of type 1 diabetes (T1D). We measured global DNA methylation (DNAm) and untargeted metabolomics prior to IA and at the time of seroconversion to IA in 92 IA cases and 91 controls from the Diabet...

Aims/hypothesis Oxylipins are lipid mediators derived from polyunsaturated fatty acids. Some oxylipins are proinflammatory (e.g. those derived from arachidonic acid [ARA]), others are pro-resolving of inflammation (e.g. those derived from α-linolenic acid [ALA], docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) and others may be both (e.g...

Gut microorganisms modulate host phenotypes and are associated with numerous health effects in humans, ranging from host responses to cancer immunotherapy to metabolic disease and obesity. However, difficulty in accurate and high-throughput functional analysis of human gut microorganisms has hindered efforts to define mechanistic connections betwee...

Oxylipins are formed from oxidation of omega-6 (n6) and omega-3 (n3) fatty acids (FAs). Evidence for inflammatory effects comes mostly from adults. Oxylipins from n6 FA (27 n6-oxylipins) and n3 FA (12 n3-oxylipins) were measured through ultra-high-performance liquid chromatography–mass spectrometry (LC-MS/MS) in plasma from 111 children at risk of...

Objective Our aim was to elucidate the role of diet in type 1 diabetes by examining combinations of nutrient intake in the progression from islet autoimmunity (IA) to type 1 diabetes. Methods We measured 2,457 metabolites and dietary intake at the time of seroconversion in 132 IA‐positive children in the prospective DAISY study. IA was defined as...

Background: American Indians (AIs) suffer disproportionately high rate of type 2 diabetes (T2D). Traditional biomarkers have limited value in predicting and tracking early onset and progression of T2D. There is an urgent need for early biomarkers in this high-risk but understudied minority population. Objective: To identify novel lipids predictive...

There is need for a single assay able to quantify the most biologically active metabolite, 1α,25-dihydroxy-vitamin-D3, and the recently discovered biologically distinct C3-epimers of 25OHD, in addition to traditional vitamin D metabolites. We developed a method of chromatographic separation and absolute quantification of the following ten forms of...

The role of diet in type 1 diabetes development is poorly understood. Metabolites, which reflect dietary response, may help elucidate this role. We explored metabolomics and lipidomics differences between 352 cases of islet autoimmunity (IA) and controls in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. We created dietar...

Drugs capable of ameliorating symptoms of depression and anxiety while also improving cognitive function and sociability are highly desirable. Anecdotal reports have suggested that serotonergic psychedelics administered in low doses on a chronic, intermittent schedule, so-called "microdosing", might produce beneficial effects on mood, anxiety, cogn...

Increased urinary acetylated polyamines (APs) are reported as cancer biomarkers in many studies. N¹,N¹²-diacetylspermine has been proposed as a biomarker indicative of different cancers in urine and plasma. N¹-Acetylspermine has previously been found to be increased in the saliva of patients with breast cancer; however, in plasma this metabolite wa...

Untargeted metabolomics by liquid chromatography–mass spectrometry generates data-rich chromatograms in the form of m/z-retention time features. Managing such datasets is a bottleneck. Many popular data processing tools, including XCMS-online and MZmine2, yield numerous false-positive peak detections. Flagging and removing such false peaks manually...

Lung cancer is the leading cause of cancer mortality in the United States with non-small cell lung cancer (NSCLC) adenocarcinoma being the most common histological type. Early perturbations in cellular metabolism are a hallmark of cancer, but the extent of these changes in early stage lung adenocarcinoma remains largely unknown. In the current stud...

Nonalcoholic fatty liver disease (NAFLD) is widespread in adults and children. Early exposure to maternal obesity or Western-style diet (WD) increases steatosis and oxidative stress in fetal liver and is associated with lifetime disease risk in the offspring. Pyrroloquinoline quinone (PQQ) is a natural antioxidant found in soil, enriched in human b...

Background Lung cancer is the leading cause of cancer mortality in the United States. Non-small cell lung cancer accounts for 85% of all lung cancers for which adenocarcinoma is the most common histological type. Management of lung cancer is hindered by high false-positive rates due to difficulty resolving between benign and malignant tumors. Bette...

Background: Recent computed tomography (CT) screening trials showed that it is effective for early detection of lung cancer, but were plagued by high false positive rates. Additional blood biomarker tests designed to complement CT screening and reduce false positive rates are highly desirable. Objective: Identify blood-based metabolite biomarker...

We have investigated the potential of metabolomics to discover blood-based biomarkers relevant to lung cancer screening and early detection. An untargeted metabolomics approach was applied to identify biomarker candidates using prediagnostic sera from the Beta-Carotene and Retinol Efficacy Trial (CARET) study. A liquid chromatography/mass spectrome...

Untargeted metabolomics was utilized in case control studies of adenocarcinoma (ADC) lung cancer in order to develop and test metabolite classifiers in serum and plasma as potential biomarkers for diagnosing lung cancer. Serum and plasma were collected and used in two independent case-control studies (ADC1 and ADC2). Controls were frequency matched...

Untargeted metabolomics by high-resolution accurate-mass LC-MS generates large data sets containing metabolic features and isotopes, adducts and in-source fragment ions. Managing such data sets in a concise and streamlined manner is a bottleneck for any metabolomics laboratory. There are many software programs, commercial or freeware, available for...

Metabolomics has the potential to yield blood and tissue based biomarkers relevant to lung cancer screening and early detection. We applied an untargeted metabolomics approach to identify blood biomarkers in a case control study using pre-diagnostic sera from a large patient cohort of current or former heavy smokers, resulting in a single, highly s...

Lung cancer is the leading cause of cancer deaths worldwide. Of the major forms of lung cancer, nonsmall cell lung cancer (NSCLC) adenocarcinoma is the most prevalent histological type. Although lowdose computed tomography (LDCT) was recently shown to reduce mortality in high-risk patients, it is limited by high false-positive rates, costs, and pot...

Adenocarcinoma, a type of non-small cell lung cancer, is the most frequently diagnosed lung cancer and the leading cause of lung cancer mortality in the United States. It is well documented that biochemical changes occur early in the transition from normal to cancer cells, but the extent to which these alterations affect tumorigenesis in adenocarci...

Current tandem mass spectral libraries for lipid annotations in metabolomics are limited in size and diversity. We provide a freely available computer-generated tandem mass spectral library of 212,516 spectra covering 119,200 compounds from 26 lipid compound classes, including phospholipids, glycerolipids, bacterial lipoglycans and plant glycolipid...