Biology subjects

Gallo, C.

Publications and source records attributed to Gallo, C..

8 recordsLinked to original sources

bioRxiv2025

SiteCELL enables on-site PBMCs purification and cryopreservation for immune single cell profiling of diverse ancestries

Single cell genomics has improved our knowledge of immune function and heterogeneity. In recent years, the steady increase in the number of cells and individuals profiled as part of large multinational projects has enabled the characterization of cellular differences across human populations and ancestries. However, methods for collecting and processing peripheral blood mononuclear cells (PBMCs) for downstream single cell sequencing are difficult to implement in remote and rural settings. This has resulted in a lack of representation of underserved communities across the Global South in current initiatives. Hence, we developed SiteCELL, a method that enables purification and cryopreservation of PBMCs from whole blood at the site of collection using minimal laboratory equipment and without electricity. By comparing matched samples of purified PBMCs, we showed that SiteCELL performs as well as ficoll density gradient (FDG), both in laboratory and rural settings. This method ensures accurate recovery of cell type proportions and excels in reducing stress and minimizing variability across sampling batches. These advantages make it particularly well suited for implementation in challenging settings across countries, thereby enabling the inclusion of underrepresented ancestries in cellular atlases.

immunology↗

bioRxiv2022

Exploring the adaptability and robustness of the central carbon metabolism of Mycoplasma pneumoniae

In this study we explored the adaptability and robustness of glycolysis and pyruvate metabolism of Mycoplasma pneumoniae (MPN). We used a dual approach, we analysed metabolomics data collected for a large number of OE and KO mutants and perturbation samples. Furthermore, we trained a dynamic model of central carbon metabolism and tested the models capacity to predict these mutants and perturbation samples as well as identify key controlling factors in central carbon metabolism. Our analysis of metabolite data as well as our model analysis indicate MPN metabolism is inherently robust against perturbations due to its network structure. Two key control hubs of central carbon metabolism were identified.

systems biology↗

bioRxiv2021

Disentangling signatures of selection before and after European colonization in Latin Americans

Throughout human evolutionary history, large-scale migrations have led to intermixing (i.e., admixture) between previously separated human groups. While classical and recent work have shown that studying admixture can yield novel historical insights, the extent to which this process contributed to adaptation remains underexplored. Here, we introduce a novel statistical model, specific to admixed populations, that identifies loci under selection while determining whether the selection likely occurred post-admixture or prior to admixture in one of the ancestral source populations. Through extensive simulations we show that this method is able to detect selection, even in recently formed admixed populations, and to accurately differentiate between selection occurring in the ancestral or admixed population. We apply this method to genome-wide SNP data of ~4,000 individuals in five admixed Latin American cohorts from Brazil, Chile, Colombia, Mexico and Peru. Our approach replicates previous reports of selection in the HLA region that are consistent with selection post-admixture. We also report novel signals of selection in genomic regions spanning 47 genes, reinforcing many of these signals with an alternative, commonly-used local-ancestry-inference approach. These signals include several genes involved in immunity, which may reflect responses to endemic pathogens of the Americas and to the challenge of infectious disease brought by European contact. In addition, some of the strongest signals inferred to be under selection in the Native American ancestral groups of modern Latin Americans overlap with genes implicated in energy metabolism phenotypes, plausibly reflecting adaptations to novel dietary sources available in the Americas.

genomics↗

bioRxiv2021

Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits - the Hispanic/Latino Anthropometry Consortium

Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite notable anthropometric variability with ancestry proportions, and a high burden of growth stunting and overweight/obesity in Hispanic/Latino populations. This address this knowledge gap, we analyzed densely-imputed genetic data in a sample of Hispanic/Latino adults, to identify and fine-map common genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (Stage 1, n=59,769) and validated our findings in 9 additional studies (HISLA Stage 2, n=9,336). We conducted a trans-ethnic GWAS with summary statistics from HISLA Stage 1 and existing consortia of European and African ancestries. In our HISLA Stage 1+2 analyses, we discovered one novel BMI locus, as well two novel BMI signals and another novel height signal, each within established anthropometric loci. In our trans-ethnic meta- analysis, we identified three additional novel BMI loci, one novel height locus, and one novel WHRadjBMI locus. We also identified three secondary signals for BMI, 28 for height, and two for WHRadjBMI. We replicated >60 established anthropometric loci in Hispanic/Latino populations at genome-wide significance--representing up to 30% of previously-reported index SNP anthropometric associations. Trans-ethnic meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our novel findings demonstrate that future studies may also benefit from leveraging differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification.

genetics↗

bioRxiv2020

Prediction Of Eye, Hair And Skin Color In Admixed Populations Of Latin America

We report an evaluation of prediction accuracy for eye, hair and skin pigmentation based on genomic and phenotypic data for over 6,500 admixed Latin Americans (the CANDELA dataset). We examined the impact on prediction accuracy of three main factors: (i) The methods of prediction, including classical statistical methods and machine learning approaches, (ii) The inclusion of non-genetic predictors, continental genetic ancestry and pigmentation SNPs in the prediction models, and (iii) Compared two sets of pigmentation SNPs: the commonly-used HIrisPlex-S set (developed in Europeans) and novel SNP sets we defined here based on genome-wide association results in the CANDELA sample. We find that Random Forest or regression are globally the best performing methods. Although continental genetic ancestry has substantial power for prediction of pigmentation in Latin Americans, the inclusion of pigmentation SNPs increases prediction accuracy considerably, particularly for skin color. For hair and eye color, HIrisPlex-S has a similar performance to the CANDELA-specific prediction SNP sets. However, for skin pigmentation the performance of HIrisPlex-S is markedly lower than the SNP set defined here, including predictions in an independent dataset of Native American data. These results reflect the relatively high variation in hair and eye color among Europeans for whom HIrisPlex-S was developed, whereas their variation in skin pigmentation is comparatively lower. Furthermore, we show that the dataset used in the training of prediction models strongly impacts on the portability of these models across Europeans and Native Americans.

genetics↗

bioRxiv2020

Temperature, but not excess of glycogen, regulate post-mortem AMPK activity in muscle of steer carcasses.

Post-mortem muscle temperature affects the rate of decline in pH in a linear manner from 37.5 {degrees}C down near 0 {degrees}C, and this pH decline is correlated with the enzymatic degradation of glycogen to lactate. This transformation occurs in an anaerobic context that includes the metabolic splice between glycogenolysis and glycolysis; and both processes are strongly upregulated by AMPK enzyme. In this study we reported changes (0.5 h and 24 h post-mortem) in muscle glycogen concentration, lactate and AMPK activity from 12 samples of Longissimus dorsi from 38 steers that produced high pH (>5.9) and normal pH (<5.8) carcasses at 24 h post-mortem. Moreover, we evaluated changes in AMPK activity in samples from both categories incubated at 37, 25, 17 and 5 {degrees}C and supplemented with exogenous glycogen. Finally, we analysed if there were structural differences between polymers from both categories. Our analyses show that enzymatic AMPK activity was significantly higher at 17 {degrees}C than at 37 {degrees}C or 25 {degrees}C (p<0.0001 and p<0.05 in samples from normal and high pH categories, respectively), and was near zero at 5 {degrees}C. On the other hand, AMPK activity did not change in relation with excess glycogen and we did not detect structural differences in the polymers present in samples from both categories. We concluded that post-mortem AMPK activity level is highly sensitive to temperature and not at in vitro changes in glycogen concentration. Their results suggest that that normal levels of pre-mortem muscle glycogen and an adequate cooling managing of carcasses are relevant to let an efficient glycogenolytic/glycolytic flow required for lactate accumulation and pH decline, trough of post-mortem AMPK signalling pathway.

biochemistry↗

bioRxiv2019

Novel genetic loci affecting facial shape variation in humans

The human face represents a combined set of highly heritable phenotypes, but knowledge on its genetic architecture remains limited despite the relevance for various fields of science and application. A series of genome-wide association studies on 78 facial shape phenotypes quantified from 3-dimensional facial images of 10,115 Europeans identified 24 genetic loci reaching genome-wide significant association, among which 17 were previously unreported. A multi-ethnic study in additional 7,917 individuals confirmed 13 loci including 8 unreported ones. A global map of polygenic face scores assembled facial features in major continental groups consistent with anthropological knowledge. Analyses of epigenomic datasets from cranial neural crest cells revealed abundant cis-regulatory activities at the face-associated genetic loci. Luciferase reporter assays in neural crest progenitor cells highlighted enhancer activities of several face-associated DNA variants. These results substantially advance our understanding of the genetic basis underlying human facial variation and provide candidates for future in-vivo functional studies.

genomics↗

bioRxiv2018

New inhibitors of Mycobacterium tuberculosis identified using systems chemical biology

New antibiotics are needed to combat rising resistance, with new Mycobacterium tuberculosis (Mtb) drugs of highest priority. Conventional whole-cell and biochemical antibiotic screens have failed. We developed a novel strategy termed PROSPECT (PRimary screening Of Strains to Prioritize Expanded Chemistry and Targets) in which we screen compounds against pools of strains depleted for essential bacterial targets. We engineered strains targeting 474 Mtb essential genes and screened pools of 100-150 strains against activity-enriched and unbiased compounds libraries, measuring > 8.5-million chemical-genetic interactions. Primary screens identified >10-fold more hits than screening wild-type Mtb alone, with chemical-genetic interactions providing immediate, direct target insight. We identified > 40 novel compounds targeting DNA gyrase, cell wall, tryptophan, folate biosynthesis, and RNA polymerase, as well as inhibitors of a novel target EfpA. Chemical optimization yielded EfpA inhibitors with potent wild-type activity, thus demonstrating PROSPECTs ability to yield inhibitors against novel targets which would have eluded conventional drug discovery.

microbiology↗