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1.
Hum Mol Genet ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33783510

RESUMO

BACKGROUND: Genome-wide association studies (GWAS) of kidney function have uncovered hundreds of loci, primarily in populations of European ancestry. We have undertaken the first continental African GWAS of estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). METHOD: We conducted GWAS of eGFR in 3288 East Africans from the Uganda General Population Cohort (GPC) and replicated in 8224 African Americans from the Women's Health Initiative. Loci attaining genome-wide significant evidence for association (p < 5x10-8) were followed up with Bayesian fine-mapping to localise potential causal variants. The predictive power of a genetic risk score (GRS) constructed from previously reported trans-ancestry eGFR lead SNPs was evaluated in the Uganda GPC. FINDINGS: We identified and validated two eGFR loci. At the GATM locus, the association signal (lead SNP rs2433603, p = 1.0x10-8) in the Uganda GPC GWAS was distinct from previously reported signals at this locus. At the HBB locus, the association signal (lead SNP rs141845179, p = 3.0x10-8) has been previously reported. The lead SNP at the HBB locus accounted for 88% of the posterior probability of causality after fine-mapping, but did not colocalise with kidney expression quantitative trait loci. The trans-ancestry GRS of eGFR was not significantly predictive into the Ugandan population. INTERPRETATION: In the first GWAS of eGFR in continental Africa, we validated two previously reported loci at GATM and HBB. At the GATM locus, the association signal was distinct from that previously reported. These results demonstrate the value of performing GWAS in continental Africans, providing a rich genomic resource to larger consortia for further discovery and fine-mapping. The study emphasizes that additional large-scale efforts in Africa are warranted to gain further insight into the genetic architecture of CKD.

2.
EBioMedicine ; 65: 103260, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33639396

RESUMO

Non-communicable diseases (NCDs) kill more than 41 million people every year, accounting for 71% of all deaths globally. The prevalence of NCDs is estimated to be higher than that of infectious diseases in Africa by 2030. Precision medicine may help with early identification of cases, resulting in timely prevention and improvement in the efficacy of treatments. However, Africa has been lagging behind in genetic research, a key component of the precision medicine initiative. A number of genomic research initiatives which could lead to translational genomics are emerging on the African continent which includes the Non-communicable Diseases Genetic Heritage Study (NCDGHS) and the Men of African Descent and Carcinoma of the Prostate (MADCaP) Network. These offer a promise that precision medicine can be applied in African countries. This review evaluates the advances of genetic studies for cancer, hypertension, type 2 diabetes and body mass index (BMI) in Africa.

3.
Comput Biol Med ; 125: 104018, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33022520

RESUMO

There is overwhelming evidence implicating Haemoglobin Subunit Beta (HBB) protein in the onset of beta thalassaemia. In this study for the first time, we used a combined SNP informatics and computer algorithms such as Neural network, Bayesian network, and Support Vector Machine to identify deleterious non-synonymous Single Nucleotide Polymorphisms (nsSNPs) present in the HBB gene. Our findings highlight three major mutation points (R31G, W38S, and Q128P) within the HBB gene sequence that have significant statistical and computational associations with the onset of beta thalassaemia. The dynamic simulation study revealed that R31G, W38S, and Q128P elicited high structural perturbation and instability, however, the wild type protein was considerably stable. Ten compounds with therapeutic potential against HBB were also predicted by structure-based virtual screening. Interestingly, the instability caused by the mutations was reversed upon binding to a ligand. This study has been able to predict potential deleterious mutants that can be further explored in the understanding of the pathological basis of beta thalassaemia and the design of tailored inhibitors.

4.
Parasit Vectors ; 13(1): 465, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912275

RESUMO

The increasing resistance to currently available insecticides in the malaria vector, Anopheles mosquitoes, hampers their use as an effective vector control strategy for the prevention of malaria transmission. Therefore, there is need for new insecticides and/or alternative vector control strategies, the development of which relies on the identification of possible targets in Anopheles. Some known and promising targets for the prevention or control of malaria transmission exist among Anopheles metabolic proteins. This review aims to elucidate the current and potential contribution of Anopheles metabolic proteins to malaria transmission and control. Highlighted are the roles of metabolic proteins as insecticide targets, in blood digestion and immune response as well as their contribution to insecticide resistance and Plasmodium parasite development. Furthermore, strategies by which these metabolic proteins can be utilized for vector control are described. Inhibitors of Anopheles metabolic proteins that are designed based on target specificity can yield insecticides with no significant toxicity to non-target species. These metabolic modulators combined with each other or with synergists, sterilants, and transmission-blocking agents in a single product, can yield potent malaria intervention strategies. These combinations can provide multiple means of controlling the vector. Also, they can help to slow down the development of insecticide resistance. Moreover, some metabolic proteins can be modulated for mosquito population replacement or suppression strategies, which will significantly help to curb malaria transmission.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32742665

RESUMO

Africa plays a central importance role in the human origins, and disease susceptibility, agriculture and biodiversity conservation. Nigeria as the most populous and most diverse country in Africa, owing to its 250 ethnic groups and over 500 different native languages is imperative to any global genomic initiative. The newly inaugurated Nigerian Bioinformatics and Genomics Network (NBGN) becomes necessary to facilitate research collaborative activities and foster opportunities for skills' development amongst Nigerian bioinformatics and genomics investigators. NBGN aims to advance and sustain the fields of genomics and bioinformatics in Nigeria by serving as a vehicle to foster collaboration, provision of new opportunities for interactions between various interdisciplinary subfields of genomics, computational biology and bioinformatics as this will provide opportunities for early career researchers. To provide the foundation for sustainable collaborations, the network organises conferences, workshops, trainings and create opportunities for collaborative research studies and internships, recognise excellence, openly share information and create opportunities for more Nigerians to develop the necessary skills to exceed in genomics and bioinformatics. NBGN currently has attracted more than 650 members around the world. Research collaborations between Nigeria, Africa and the West will grow and all stakeholders, including funding partners, African scientists, researchers across the globe, physicians and patients will be the eventual winners. The exponential membership growth and diversity of research interests of NBGN just within weeks of its establishment and the unanticipated attendance of its activities suggest the significant importance of the network to bioinformatics and genomics research in Nigeria.

7.
Nat Commun ; 11(1): 3849, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737300

RESUMO

Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr Virus (EBV) establish life-long infections and are associated with malignancies. Striking geographic variation in incidence and the fact that virus alone is insufficient to cause disease, suggests other co-factors are involved. Here we present epidemiological analysis and genome-wide association study (GWAS) in 4365 individuals from an African population cohort, to assess the influence of host genetic and non-genetic factors on virus antibody responses. EBV/KSHV co-infection (OR = 5.71(1.58-7.12)), HIV positivity (OR = 2.22(1.32-3.73)) and living in a more rural area (OR = 1.38(1.01-1.89)) are strongly associated with immunogenicity. GWAS reveals associations with KSHV antibody response in the HLA-B/C region (p = 6.64 × 10-09). For EBV, associations are identified for VCA (rs71542439, p = 1.15 × 10-12). Human leucocyte antigen (HLA) and trans-ancestry fine-mapping substantiate that distinct variants in HLA-DQA1 (p = 5.24 × 10-44) are driving associations for EBNA-1 in Africa. This study highlights complex interactions between KSHV and EBV, in addition to distinct genetic architectures resulting in important differences in pathogenesis and transmission.


Assuntos
Anticorpos Antivirais/biossíntese , Resistência à Doença/genética , Infecções por Vírus Epstein-Barr/genética , Infecções por Henipavirus/genética , Interações Hospedeiro-Patógeno/genética , Sarcoma de Kaposi/genética , Adolescente , Adulto , Antígenos Virais/genética , Antígenos Virais/imunologia , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/imunologia , Coinfecção , Infecções por Vírus Epstein-Barr/epidemiologia , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/virologia , Antígenos Nucleares do Vírus Epstein-Barr/genética , Antígenos Nucleares do Vírus Epstein-Barr/imunologia , Feminino , Expressão Gênica , Estudo de Associação Genômica Ampla , HIV/genética , HIV/imunologia , HIV/patogenicidade , Cadeias alfa de HLA-DQ/genética , Cadeias alfa de HLA-DQ/imunologia , Infecções por Henipavirus/epidemiologia , Infecções por Henipavirus/imunologia , Infecções por Henipavirus/virologia , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/patogenicidade , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/imunologia , Herpesvirus Humano 8/patogenicidade , Interações Hospedeiro-Patógeno/imunologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , População Rural , Sarcoma de Kaposi/epidemiologia , Sarcoma de Kaposi/imunologia , Sarcoma de Kaposi/virologia , Uganda/epidemiologia , População Urbana
8.
J Affect Disord ; 275: 7-13, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32658827

RESUMO

BACKGROUND: The 1994 genocide against Tutsi resulted in a massive death toll that reached one million people. Despite the tremendous efforts made to mitigate the adverse effects of the genocide, a substantial burden of mental health disorders still exists including the notably high prevalence of post-traumatic stress disorder (PTSD) among genocide survivors. However, a synthesized model of PTSD vulnerability in this population is currently lacking. METHODS: A meta-analysis of 19 original research studies that reported PTSD prevalence (n = 12,610). Medline-PubMed and Science.gov were key search engines. Random-Effects Model (k = 19; tau^2 estimator: DL) was applied. Data extraction, synthesis, and meta-analysis were carried out using R. RESULTS: The total of 2957 out of 11,746 individuals suffered from PTSD. The summary proportion is 25% (95% CI=0.16,0.36). The tau^2 is 0.06 (95% CI=0.03,0.14) in the absence of subgroups, and the Q-statistic is 2827.65 (p<0.0001), all of which suggests high heterogeneity in the effect sizes. Year of data collection and Year of publication were significant moderators. PTSD pooled prevalence in the genocide survivor category was estimated at 37% (95% CI=0.21,0.56). CONCLUSION: The PTSD prevalence among genocide survivors is considerably higher compared to the general Rwandan population. The burden of PTSD in the general Rwandan population declined significantly over time, likely due to treatment of symptoms through strong national mental health programs, peace building and resolution of symptoms over time. To the best of our knowledge little evidence has reported the burden of PTSD prevalence in African post conflict zones particularly in Rwanda. LIMITATION: Limitations of our review include the use of retrospective studies and studies with very small sample sizes, as well as language criterion.

9.
EBioMedicine ; 54: 102721, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32268272
10.
F1000Res ; 8: 1135, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824661

RESUMO

Background: Basic and clinical scientific research at the University of South Florida (USF) have intersected to support a multi-faceted approach around a common focus on rare iron-related diseases. We proposed a modified version of the National Center for Biotechnology Information's (NCBI) Hackathon-model to take full advantage of local expertise in building "Iron Hack", a rare disease-focused hackathon. As the collaborative, problem-solving nature of hackathons tends to attract participants of highly-diverse backgrounds, organizers facilitated a symposium on rare iron-related diseases, specifically porphyrias and Friedreich's ataxia, pitched at general audiences. Methods: The hackathon was structured to begin each day with presentations by expert clinicians, genetic counselors, researchers focused on molecular and cellular biology, public health/global health, genetics/genomics, computational biology, bioinformatics, biomolecular science, bioengineering, and computer science, as well as guest speakers from the American Porphyria Foundation (APF) and Friedreich's Ataxia Research Alliance (FARA) to inform participants as to the human impact of these diseases. Results: As a result of this hackathon, we developed resources that are relevant not only to these specific disease-models, but also to other rare diseases and general bioinformatics problems. Within two and a half days, "Iron Hack" participants successfully built collaborative projects to visualize data, build databases, improve rare disease diagnosis, and study rare-disease inheritance. Conclusions: The purpose of this manuscript is to demonstrate the utility of a hackathon model to generate prototypes of generalizable tools for a given disease and train clinicians and data scientists to interact more effectively.


Assuntos
Ataxia de Friedreich , Porfirias , Bases de Dados Factuais , Humanos , Ferro , Doenças Raras , Estados Unidos
11.
Cell ; 179(4): 984-1002.e36, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31675503

RESUMO

Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans was best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, hematological, lipid, and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Predisposição Genética para Doença , Genoma Humano/genética , Genômica , Feminino , Frequência do Gene/genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Uganda/epidemiologia , Sequenciamento Completo do Genoma
12.
Front Genet ; 10: 334, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31080455

RESUMO

Genome-wide association studies (GWAS) have found hundreds of novel loci associated with full blood count (FBC) phenotypes. However, most of these studies were performed in a single phenotype framework without putting into consideration the clinical relatedness among traits. In this work, in addition to the standard univariate GWAS, we also use two different multivariate methods to perform the first multiple traits GWAS of FBC traits in ∼7000 individuals from the Ugandan General Population Cohort (GPC). We started by performing the standard univariate GWAS approach. We then performed our first multivariate method, in this approach, we tested for marker associations with 15 FBC traits simultaneously in a multivariate mixed model implemented in GEMMA while accounting for the relatedness of individuals and pedigree structures, as well as population substructure. In this analysis, we provide a framework for the combination of multiple phenotypes in multivariate GWAS analysis and show evidence of multi-collinearity whenever the correlation between traits exceeds the correlation coefficient threshold of r 2 >=0.75. This approach identifies two known and one novel loci. In the second multivariate method, we applied principal component analysis (PCA) to the same 15 correlated FBC traits. We then tested for marker associations with each PC in univariate linear mixed models implemented in GEMMA. We show that the FBC composite phenotype as assessed by each PC expresses information that is not completely encapsulated by the individual FBC traits, as this approach identifies three known and five novel loci that were not identified using both the standard univariate and multivariate GWAS methods. Across both multivariate methods, we identified six novel loci. As a proof of concept, both multivariate methods also identified known loci, HBB and ITFG3. The two multivariate methods show that multivariate genotype-phenotype methods increase power and identify novel genotype-phenotype associations not found with the standard univariate GWAS in the same dataset.

13.
Glob Heart ; 12(2): 91-98, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28302555

RESUMO

BACKGROUND: Although pockets of bioinformatics excellence have developed in Africa, generally, large-scale genomic data analysis has been limited by the availability of expertise and infrastructure. H3ABioNet, a pan-African bioinformatics network, was established to build capacity specifically to enable H3Africa (Human Heredity and Health in Africa) researchers to analyze their data in Africa. Since the inception of the H3Africa initiative, H3ABioNet's role has evolved in response to changing needs from the consortium and the African bioinformatics community. OBJECTIVES: H3ABioNet set out to develop core bioinformatics infrastructure and capacity for genomics research in various aspects of data collection, transfer, storage, and analysis. METHODS AND RESULTS: Various resources have been developed to address genomic data management and analysis needs of H3Africa researchers and other scientific communities on the continent. NetMap was developed and used to build an accurate picture of network performance within Africa and between Africa and the rest of the world, and Globus Online has been rolled out to facilitate data transfer. A participant recruitment database was developed to monitor participant enrollment, and data is being harmonized through the use of ontologies and controlled vocabularies. The standardized metadata will be integrated to provide a search facility for H3Africa data and biospecimens. Because H3Africa projects are generating large-scale genomic data, facilities for analysis and interpretation are critical. H3ABioNet is implementing several data analysis platforms that provide a large range of bioinformatics tools or workflows, such as Galaxy, the Job Management System, and eBiokits. A set of reproducible, portable, and cloud-scalable pipelines to support the multiple H3Africa data types are also being developed and dockerized to enable execution on multiple computing infrastructures. In addition, new tools have been developed for analysis of the uniquely divergent African data and for downstream interpretation of prioritized variants. To provide support for these and other bioinformatics queries, an online bioinformatics helpdesk backed by broad consortium expertise has been established. Further support is provided by means of various modes of bioinformatics training. CONCLUSIONS: For the past 4 years, the development of infrastructure support and human capacity through H3ABioNet, have significantly contributed to the establishment of African scientific networks, data analysis facilities, and training programs. Here, we describe the infrastructure and how it has affected genomics and bioinformatics research in Africa.


Assuntos
Pesquisa Biomédica/métodos , Biologia Computacional/tendências , Genômica/métodos , África , Humanos
14.
Nat Commun ; 5: 5345, 2014 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-25373335

RESUMO

Isolated populations are emerging as a powerful study design in the search for low-frequency and rare variant associations with complex phenotypes. Here we genotype 2,296 samples from two isolated Greek populations, the Pomak villages (HELIC-Pomak) in the North of Greece and the Mylopotamos villages (HELIC-MANOLIS) in Crete. We compare their genomic characteristics to the general Greek population and establish them as genetic isolates. In the MANOLIS cohort, we observe an enrichment of missense variants among the variants that have drifted up in frequency by more than fivefold. In the Pomak cohort, we find novel associations at variants on chr11p15.4 showing large allele frequency increases (from 0.2% in the general Greek population to 4.6% in the isolate) with haematological traits, for example, with mean corpuscular volume (rs7116019, P=2.3 × 10(-26)). We replicate this association in a second set of Pomak samples (combined P=2.0 × 10(-36)). We demonstrate significant power gains in detecting medical trait associations.


Assuntos
Deriva Genética , Variação Genética/genética , Genética Populacional , Genótipo , Mutação de Sentido Incorreto/genética , População/genética , Adolescente , Células Sanguíneas/citologia , Tamanho Celular , Estudos de Coortes , Frequência do Gene/genética , Estudo de Associação Genômica Ampla , Grécia , Haplótipos/genética , Humanos , Fenótipo , Isolamento Social
16.
Source Code Biol Med ; 9: 10, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24829612

RESUMO

BACKGROUND: A multi-million dollar research initiative involving the National Institutes of Health (NIH), Wellcome Trust and African scientists has been launched. The initiative, referred to as H3Africa, is an acronym that stands for Human Heredity and Health in Africa. Here, we outline what this initiative is set to achieve and the latest commitments of the key players as at October 2013. FINDINGS: The initiative has so far been awarded over $74 million in research grants. During the first set of awards announced in 2012, the NIH granted $5 million a year for a period of five years, while the Wellcome Trust doled out at least $12 million over the period to the research consortium. This was in addition to Wellcome Trust's provision of administrative support, scientific consultation and advanced training, all in collaboration with the African Society for Human Genetics. In addition, during the second set of awards announced in October 2013, the NIH awarded to the laudable initiative 10 new grants of up to $17 million over the next four years. CONCLUSIONS: H3Africa is poised to transform the face of research in genomics, bioinformatics and health in Africa. The capacity of African scientists will be enhanced through training and the better research facilities that will be acquired. Research collaborations between Africa and the West will grow and all stakeholders, including the funding partners, African scientists, scientists across the globe, physicians and patients will be the eventual winners.

17.
PLoS Comput Biol ; 10(4): e1003516, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24763310

RESUMO

Over the past few decades, major advances in the field of molecular biology, coupled with advances in genomic technologies, have led to an explosive growth in the biological data generated by the scientific community. The critical need to process and analyze such a deluge of data and turn it into useful knowledge has caused bioinformatics to gain prominence and importance. Bioinformatics is an interdisciplinary research area that applies techniques, methodologies, and tools in computer and information science to solve biological problems. In Nigeria, bioinformatics has recently played a vital role in the advancement of biological sciences. As a developing country, the importance of bioinformatics is rapidly gaining acceptance, and bioinformatics groups comprised of biologists, computer scientists, and computer engineers are being constituted at Nigerian universities and research institutes. In this article, we present an overview of bioinformatics education and research in Nigeria. We also discuss professional societies and academic and research institutions that play central roles in advancing the discipline in Nigeria. Finally, we propose strategies that can bolster bioinformatics education and support from policy makers in Nigeria, with potential positive implications for other developing countries.


Assuntos
Biologia Computacional , Biologia Computacional/educação , Nigéria
18.
PLoS Comput Biol ; 10(2): e1003497, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24586140

RESUMO

As part of the International Society for Computational Biology Student Council (ISCB-SC), Regional Student Groups (RSGs) have helped organise workshops in the emerging fields of bioinformatics and computational biology. Workshops are a great way for students to gain hands-on experience and rapidly acquire knowledge in advanced research topics where curriculum-based education is yet to be developed. RSG workshops have improved dissemination of knowledge of the latest bioinformatics techniques and resources among student communities and young scientists, especially in developing nations. This article highlights some of the benefits and challenges encountered while running RSG workshops. Examples cover a variety of subjects, including introductory bioinformatics and advanced bioinformatics, as well as soft skills such as networking, career development, and socializing. The collective experience condensed in this article is a useful starting point for students wishing to organise their own tailor-made workshops.


Assuntos
Biologia Computacional/educação , Educação/métodos , Biologia Computacional/organização & administração , Educação/organização & administração , Sociedades Científicas
19.
Infect Genet Evol ; 20: 389-95, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24121016

RESUMO

Plasmodium falciparum (PF) is the most severe malaria parasite. It is developing resistance quickly to existing drugs making it indispensable to discover new drugs. Effective drugs have been discovered targeting metabolic enzymes of the parasite. In order to predict new drug targets, computational methods can be used employing database information of metabolism. Using this data, we performed recently a computational network analysis of metabolism of PF. We analyzed the topology of the network to find reactions which are sensitive against perturbations, i.e., when a single enzyme is blocked by drugs. We now used a refined network comprising also the host enzymes which led to a refined set of the five targets glutamyl-tRNA (gln) amidotransferase, hydroxyethylthiazole kinase, deoxyribose-phophate aldolase, pseudouridylate synthase, and deoxyhypusine synthase. It was shown elsewhere that glutamyl-tRNA (gln) amidotransferase of other microorganisms can be inhibited by 6-diazo-5-oxonorleucine. Performing a half maximal inhibitory concentration (IC50) assay, we showed, that 6-diazo-5-oxonorleucine is also severely affecting viability of PF in blood plasma of the human host. We confirmed this by an in vivo study observing Plasmodium berghei infected mice.


Assuntos
Compostos Azo/química , Malária Falciparum/tratamento farmacológico , Transferases de Grupos Nitrogenados/antagonistas & inibidores , Norleucina/análogos & derivados , Plasmodium falciparum/efeitos dos fármacos , Animais , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Compostos Azo/farmacologia , Simulação por Computador , Eritrócitos/parasitologia , Humanos , Camundongos , Norleucina/química , Norleucina/farmacologia , Proteínas de Protozoários/antagonistas & inibidores
20.
Methods Mol Biol ; 993: 39-65, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23568463

RESUMO

Resistance to drugs that treat infectious disease is a major problem worldwide. The rapid emergence of drug resistance is not well understood. We present two in silico models for the discovery of drug resistance mechanisms and for combating the evolution of resistance, respectively. In the first model, we computationally investigated subgraphs of a biological interaction network that show substantial adaptations when cells transcriptionally respond to a changing environment or treatment. As a case study, we investigated the response of the malaria parasite Plasmodium falciparum to chloroquine and tetracycline treatments. The second model involves a machine learning technique that combines clustering, common distance similarity measurements, and hierarchical clustering to propose new combinations of drug targets.


Assuntos
Biologia Computacional/métodos , Resistência a Medicamentos , Algoritmos , Inteligência Artificial , Cloroquina/farmacologia , Técnicas de Inativação de Genes , Humanos , Redes e Vias Metabólicas/efeitos dos fármacos , Mutação , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/genética , Plasmodium falciparum/metabolismo , Tetraciclina/farmacologia , Transcriptoma/efeitos dos fármacos
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