Papers by Felipe J Chaves
BMC Genomics, Nov 24, 2021
Background: Genome assembly of viruses with high mutation rates, such as Norovirus and other RNA ... more Background: Genome assembly of viruses with high mutation rates, such as Norovirus and other RNA viruses, or from metagenome samples, poses a challenge for the scientific community due to the coexistence of several viral quasispecies and strains. Furthermore, there is no standard method for obtaining whole-genome sequences in nonrelated patients. After polyA RNA isolation and sequencing in eight patients with acute gastroenteritis, we evaluated two de Bruijn graph assemblers (SPAdes and MEGAHIT), combined with four different and common pre-assembly strategies, and compared those yielding whole genome Norovirus contigs. Results: Reference-genome guided strategies with both host and target virus did not present any advantages compared to the assembly of non-filtered data in the case of SPAdes, and in the case of MEGAHIT, only host genome filtering presented improvements. MEGAHIT performed better than SPAdes in most samples, reaching complete genome sequences in most of them for all the strategies employed. Read binning with CD-HIT improved assembly when paired with different analysis strategies, and more notably in the case of SPAdes. Conclusions: Not all metagenome assemblies are equal and the choice in the workflow depends on the species studied and the prior steps to analysis. We may need different approaches even for samples treated equally due to the presence of high intra host variability. We tested and compared different workflows for the accurate assembly of Norovirus genomes and established their assembly capacities for this purpose.
BMJ Open Diabetes Research & Care
IntroductionMetabolic syndrome (MetS) is an important predictor of cardiovascular mortality. Iden... more IntroductionMetabolic syndrome (MetS) is an important predictor of cardiovascular mortality. Identification of occurrence and regression trends of MetS could permit elaboration of preventive strategies with new targets. The objective of this study was to analyze the occurrence and regression rates of MetS and its associated factors in the representative cohort of Spain of the [email protected] study.Research design and methodsThe [email protected] study is a prospective cohort where 5072 people representative of the Spanish population over 18 years of age were randomly selected between 2009 and 2010. Follow-up was a median of 7.5 (IQR 7.2–7.9) years, with 2408 (47%) participating subjects. A total of 1881 (78%) subjects had all the pertinent data available and were included in this study.ResultsOf the 1146 subjects without baseline criteria for MetS, 294 (25.7%) developed MetS during follow-up, while of the 735 patients with prior MetS, 148 (20.1%) presented regression. Adjusted MetS incidence per ...
Environmental Health
Background Recent reports have suggested that air pollution may impact thyroid function, although... more Background Recent reports have suggested that air pollution may impact thyroid function, although the evidence is still scarce and inconclusive. In this study we evaluated the association of exposure to air pollutants to thyroid function parameters in a nationwide sample representative of the adult population of Spain. Methods The [email protected] study is a national, cross-sectional, population-based survey which was conducted in 2008-2010 using a random cluster sampling of the Spanish population. The present analyses included 3859 individuals, without a previous thyroid disease diagnosis, and with negative thyroid peroxidase antibodies (TPO Abs) and thyroid-stimulating hormone (TSH) levels of 0.1-20 mIU/L. Participants were assigned air pollution concentrations for particulate matter <2.5μm (PM2.5) and Nitrogen Dioxide (NO2), corresponding to the health examination year, obtained by means of modeling combined with measurements taken at air quality stations (CHIMERE chemistry-transport...
Reactome includes graphical illustrations of broad biological processes that can help scientists ... more Reactome includes graphical illustrations of broad biological processes that can help scientists understand the relationship between process and pathway. Where possible the illustration and pathway diagram are organized with a similar layout to aid comprehension.
Scientific Reports, 2020
Our aim was to determine the incidence of type 2 diabetes mellitus in a nation-wide population ba... more Our aim was to determine the incidence of type 2 diabetes mellitus in a nation-wide population based cohort from Spain ([email protected] study). The target was the Spanish population. In total 5072 people older than 18 years,were randomly selected from all over Spain). Socio-demographic and clinical data, survey on habits (physical activity and food consumption) and weight, height, waist, hip and blood pressure were recorder. A fasting blood draw and an oral glucose tolerance test were performed. Determinations of serum glucose were made. In the follow-up the same variables were collected and HbA1c was determined. A total of 2408 subjects participated in the follow-up. In total, 154 people developed diabetes (6.4% cumulative incidence in 7.5 years of follow-up). The incidence of diabetes adjusted for the structure of age and sex of the Spanish population was 11.6 cases/1000 person-years (IC95% = 11.1–12.1). The incidence of known diabetes was 3.7 cases/1000 person-years (IC95% = 2.8–4.6). ...
Obesity (Silver Spring, Md.), Apr 1, 2017
To analyze the reference range of thyroid-stimulating hormone (TSH) in different BMI categories a... more To analyze the reference range of thyroid-stimulating hormone (TSH) in different BMI categories and its impact on the classification of hypothyroidism. The study included 3,928 individuals free of thyroid disease (without previous thyroid disease, no interfering medications, TSH <10 µUI/mL and thyroid peroxidase antibodies [TPO Abs] <50 IU/mL) who participated in a national, cross-sectional, population-based study and were representative of the adult population of Spain. Data gathered included clinical and demographic characteristics, physical examination, and blood and urine sampling. TSH, free thyroxine, free triiodothyronine, and TPO Ab were analyzed by electrochemiluminescence (E170, Roche Diagnostics, Basel, Switzerland). The reference range (p2.5-97.5) for TSH was estimated as 0.6 to 4.8 µUI/mL in the underweight category (BMI<20 kg/m(2) ), 0.6 to 5.5 µUI/mL in the normal-weight category (BMI 20-24.9 kg/m(2) ), 0.6 to 5.5 µUI/mL in the overweight category (BMI 25-29.9...
Journal of Thoracic Oncology, 2016
Background: Although it was initially thought many driver alterations were mutually exclusive, it... more Background: Although it was initially thought many driver alterations were mutually exclusive, it might not be so. These pathways may interact in a dynamic way. Whether these mutations are present in different cellular clones that emerge as a result of treatment pressure or they co-exist in the same cell is not yet fully clear. Methods: Between Nov. 2011Aug. 2014 clinical data from consecutive newly diagnosed lung cancer patients in our center were prospectively collected in a database. Mutational analysis of EGFR, KRAS, BRAF and PI3K as well as ALK rearrangement was determined in all metastatic Nsq-NSCLC. EGFR mutational analysis was carried out using next generation sequencing using the Cobas and Junior diagnostic method. KRAS, BRAF and Pi3Kanalysis was determined by next generation sequencing using Sequencing Multiplex and Junior System. ALK rearrangement was carried out by FISH and confirmed by IHQ (D5F3, Ventana diagnostics). Results: 327 patients were diagnosed with Nsq-NSCLC. 216 (66%) of the 327 patients had EGFR analysed, 132 (40.3%) KRAS, 128 (39.1%) BRAF, 122 (37.3%) PI3K and 126 (38.5%) ALK. Of the 216 with EGFR determination, 58 (26.8%) harbored EGFR mutations. Exon 19 deletions (44.4%), exon 21 mutations (L858R and L861Q-47.2%), exon 18 mutations G719A/C/S (13.8%). Fifty four (40.9%) KRAS mutations, 4 (3.1%) BRAF mutations, 12 (9.8%) PI3K mutations and 8 (6.3%) ALK rearranged .14 had coexistent mutations: 2 EGFR/ALK rearrangements , 9 EGFR/KRAS, 4 EGFR/PI3K, and 2 EGFR/BRAF. 3 patients had triple mutations in EGFR/BRAF/ALK, and 2 in EGFR/KRAS/PI3K. Conclusions: We show that these mutations may co-exist previous to receiving targeted therapy. Whether they represent a primary or acquired resistance to targeted therapy is important to determine (data to be presented on the tissue origin-primary tumor vs metastasis). In our series, 78.5% of the patients were heavy smokers. Most patients were not exposed to targeted therapy, but of those who were, most did not respond. Legal entity responsible for the study:
Scientific reports, Jan 24, 2016
American Journal of Hypertension, 2004
The objective was to study factors related to the changes induced by antihypertensive treatment o... more The objective was to study factors related to the changes induced by antihypertensive treatment on oxidative status, antioxidant activities, and reactive oxygen species by-products in whole blood and mononuclear peripheral cells. Eighty-nine hypertensive patients (mean age 46 years, 46 men, average 24-h blood pressure 139/88 mm Hg, body mass index 29) were included. After 3 months of nonrandomized allocation to antihypertensive treatment (20 nonpharmacologic, 36 -blockers, 33 angiotensin receptor blocker), oxidized/reduced glutathione ratio and malondialdehyde were significantly reduced, and the activity of superoxide dismutase, catalase, and glutathione peroxidase was significantly increased in both whole blood and peripheral mononuclear cells. The content of damaged base 8-oxo-2=-deoxyguanosine in nuclear and mitochondrial DNA in hypertensive subjects was also significantly reduced during the antihypertensive treatment. In a group of 42 subjects, the oxidative stress was further reduced and the antioxidant enzyme activities further increased after 12 months of antihypertensive treatment. The changes were independent of the kind of antihypertensive treatment. In conclusion, antihypertensive treatment improved the increased oxidative stress and the decreased antioxidant mechanisms. It is independent of the type of treatment and the beneficial effect of treatment increases over time.
The Journal of Clinical Endocrinology & Metabolism, 2013
Background: Prospective longitudinal studies evaluating the relevance of "Metabolically Healthy b... more Background: Prospective longitudinal studies evaluating the relevance of "Metabolically Healthy but Obese" (MHO) phenotype at risk for type 2 diabetes mellitus (T2D) and cardiovascular diseases are few and results are contradictory. Methods: As a representative of the general population, 1051 individuals were evaluated in 1997-1998 and re-evaluated after 6 years and 11 years. Subjects without known T2D were given an oral glucose tolerance test. Anthropometric and biochemical variables were measured. Four sets of criteria were considered to define MHO subjects besides body mass index Ն30 kg/m 2 : A: Homeostatic Model of Assessment-Insulin Resistance Index (HOMA-IR) Ͻ90th percentile; B: HOMA-IR Ͻ90th percentile, high-density lipoprotein cholesterol Ͼ40 mg/dL in men and high-density lipoprotein cholesterol Ͼ50 mg/dL in women, triglycerides Ͻ150 mg/dL, fasting glucose Ͻ110 mg/dL, and blood pressure Յ140/90 mm Hg; C: HOMA-IR Ͻ90th percentile, triglycerides Ͻ150 mg/dL, fasting glucose Ͻ110 mg/dL, and blood pressure Յ140/90 mm Hg; D: HOMA-IR Ͻ90th percentile, triglycerides Ͻ150 mg/dL, and fasting glucose Ͻ110 mg/dL. Subjects with T2D at baseline were excluded from the calculations of incidence of T2D. Results: The baseline prevalence of MHO phenotype varied between 3.0% and 16.9%, depending on the set of criteria chosen. Metabolically nonhealthy obese subjects were at highest risk for becoming diabetic after 11 years of follow-up (odds ratio ϭ 8.20; 95% confidence interval ϭ 2.72-24.72; P Ͻ .0001). In MHO subjects the risk for becoming diabetic was lower than in metabolically nonhealthy obese subjects, but this risk remained significant (odds ratio ϭ 3.13; 95% confidence interval ϭ 1.07-9.17; P ϭ .02). In subjects who lost weight during the study, the association between MHO phenotype and T2D incidence disappeared, even after adjusting for HOMA-IR. Conclusions: The results suggest that MHO is a dynamic concept that should be taken into account over time. As a clinical entity, it may be questionable.
Human Mutation, 2003
We screened index cases from 410 Spanish breast/ovarian cancer families and 214 patients (19 of t... more We screened index cases from 410 Spanish breast/ovarian cancer families and 214 patients (19 of them males) with breast cancer for germ-line mutations in the BRCA1 and BRCA2 genes, using SSCP, PTT, CSGE, DGGE, and direct sequencing. We identified 60 mutations in BRCA1 and 53 in BRCA2. Of the 53 distinct mutations observed, 11 are novel and 12 have been reported only in Spanish families (41.5%). The prevalence of mutations in this set of families was 26.3%, but the percentage was higher in the families with breast and ovarian cancer (52.1%). The lowest proportion of mutations was found in the site-specific female breast cancer families (15.4%). Of the families with male breast cancer cases, 59.1% presented mutations in the BRCA2 gene. We found a higher frequency of ovarian cancer associated with mutations localized in the 5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; end of the BRCA1 gene, but there was no association between the prevalence of this type of cancer and mutations situated in the ovarian cancer cluster region (OCCR) region of exon 11 of the BRCA2 gene. The mutations 187_188delAG,…
Philosophical transactions of the Royal Society of London. Series B, Biological sciences, Jan 5, 2018
We explored the association of metal levels with subclinical atherosclerosis and epigenetic chang... more We explored the association of metal levels with subclinical atherosclerosis and epigenetic changes in relevant biological pathways. Whole blood DNA Infinium Methylation 450 K data were obtained from 23 of 73 middle age men without clinically evident cardiovascular disease (CVD) who participated in the Aragon Workers Health Study in 2009 (baseline visit) and had available baseline urinary metals and subclinical atherosclerosis measures obtained in 2010-2013 (follow-up visit). The median metal levels were 7.36 µg g, 0.33 µg g, 0.11 µg g and 0.07 µg g, for arsenic (sum of inorganic and methylated species), cadmium, antimony and tungsten, respectively. Urine cadmium and tungsten were associated with femoral and carotid intima-media thickness, respectively (Pearson's = 0.27; = 0.03 in both cases). Among nearest genes to identified differentially methylated regions (DMRs), 46% of metal-DMR genes overlapped with atherosclerosis-DMR genes ( < 0.001). Pathway enrichment analysis of a...
Human Mutation, Oct 9, 2001
Mutations underlying FH in Spain are largely unknown because only a few and limited surveys have ... more Mutations underlying FH in Spain are largely unknown because only a few and limited surveys have been carried out on Spanish FH patients up to now. To gain information on this issue, we have analysed a group of 113 unrelated Spanish FH patients from an eastern area of Spain (Valencian Community). We have screened the LDLR gene by Southern blot and PCR-SSCP analysis to detect large rearrangements and small mutations, respectively. In addition, we have screened the Apo B gene for mutations known to cause FDB by PCR-SSCP analysis. We have identified a total of 47 different mutations in the LDLR gene (5 large rearrangements, and 42 small mutations, which were characterized by DNA sequencing), 19 of which have not been described in other populations (Valencia-1 to -4, 112insA, P160R, 790DelATGA, 920insTCAG, G642E, and the ten novel mutations E246A, 884delT, I289T, S305F, Q328X, Y354C, I603del, 2312-3C&amp;amp;amp;amp;amp;amp;amp;amp;gt;A, V779M, and N804K). Three of these mutations (15%) were present in more than 1 proband, being mutation 112insA the most prevalent (frequency approximately 8%) in our sample. The Apo B gene R3500Q mutation was found in only one patient and no underlying defect was found in about 27% of patients. Our data support the notion that Spaniards represent a heterogeneous population with its own spectrum of LDLR gene mutations and that, in our population, FDB has a lower frequency or a milder expression than in central Europe countries.
International Journal of Epidemiology, Apr 9, 2019
Background: The association of low-level exposure to metals and metal mixtures with cardiovascula... more Background: The association of low-level exposure to metals and metal mixtures with cardiovascular incidence in the general population has rarely been studied. We flexibly evaluated the association of urinary metals and metal mixtures concentrations with cardiovascular diseases in a representative sample of a general population from Spain. Methods: Urine antimony (Sb), barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), molybdenum (Mo), vanadium (V) and zinc (Zn) were measured in 1171 adults without clinical cardiovascular diseases, who participated in the Hortega Study. Cox proportional hazard models were used for evaluating the association between single
medRxiv (Cold Spring Harbor Laboratory), Jul 28, 2023
This research aims to evaluate the Type 2 Diabetes (T2D) diagnosis and prognosis power from heter... more This research aims to evaluate the Type 2 Diabetes (T2D) diagnosis and prognosis power from heterogeneous environmental, lifestyle and biochemistry data. Model estimation has previously addressed three main actions as: 1) Missingvalue imputation using specific univariant and multivariant imputers accommodated to each particular feature; 2) Quasi-constancy detection in variables; 3) Constructing geographical pollution and rent data from municipality information. Next, different T2D diagnosis and prognosis models are fitted and evaluated, showing increasing performance as more specific features become available while the prediction cost rises as a consequence of requiring more specific data. Finally, four models are obtained: two of them for T2D diagnosis and the other two for T2D prognosis respectively, with performances ranging from 73.3 to 95.41 AUC-ROC. One pair of diagnosis and prognosis models were thought for a global testing that can be done in general locations by only asking general lifestyle-related questions. On the other hand, the other pair, which achieves higher performances, is thought to be applied in a clinical environment where it is easy to obtain more specific biochemistry measures.
Biomedicines, Jun 9, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Journal of Hypertension, Jun 1, 2023
European Journal of Internal Medicine, Aug 1, 2022
The Journal of Clinical Endocrinology and Metabolism, Oct 1, 2001
International Journal of Obesity
Background/Objectives Although vascular endothelial growth factor b (VEGFb) might have an impact ... more Background/Objectives Although vascular endothelial growth factor b (VEGFb) might have an impact on the development of obesity, diabetes and related disorders, the possible relationship between VEGFb serum levels and the incidence of these metabolic complications in humans is still unknown. The aim of our study was to evaluate the association between VEGFb serum levels and the new-onset of metabolic syndrome (MS) and its components in the Spanish adult population after 7.5 years of follow-up. Subjects/Methods A total of 908 subjects from the [email protected] cohort study without MS at cross-sectional stage according to International Diabetes Federation (IDF) or Adult Treatment Panel III (ATP-III) criteria were included. Additionally, five sub-populations were grouped according to the absence of each MS component at baseline. Socio-demographic, anthropometric and clinical data were recorded. The Short Form of International Physical Activity Questionnaire (SF-IPAQ) was used to estimate physi...
Uploads
Papers by Felipe J Chaves