Personalizing medicine in Africa: current state, progress and challenges

Personalized medicine has been identified as a powerful tool for addressing the myriad of health issues facing different health systems globally. Although recent studies have expanded our understanding of how different factors such as genetics and the environment play significant roles in affecting the health of individuals, there are still several other issues affecting their translation into personalizing health interventions globally. Since African populations have demonstrated huge genetic diversity, there is a significant need to apply the concepts of personalized medicine to overcome various African-specific health challenges. Thus, we review the current state, progress, and challenges facing the adoption of personalized medicine in Africa with a view to providing insights to critical stakeholders on the right approach to deploy

Systems Biology And The Development Of Vaccines And Drugs For Malaria Treatments

The sequencing race has ended and the functional race has already begun. Microarray technology enables simultaneous gene expression analysis of thousands of genes, enabling a snapshot of an organisms' transcriptome at an unprecedented resolution. The close correlation between gene transcription and function, allow the inference of biological processes from the assessed transcriptome profile. Among the sophisticated analytical problems in microarray technology at the front and back ends respectively, are the selection of optimal DNA oligos and computational analysis of the genes expression. In this review paper, we analyse important methods in use today in customized oligos design. In the course of executing this, we discovered that the oligos designer algorithm hanged on gene PFA0135w of chromosome 1, while designing oligos for the gene sequences of Plasmodium falciparum . We do not know the reason for this yet, as the algorithm runs on other sequences like the yeast ( Saccharomyces cervisiae ) and Neurospora crassa . We conclude the paper highlighting the procedures encompassing the back end phase and discuss their application to the development of vaccines and drugs for malaria treatment. Note that, malaria is the cause of significant global morbidity and mortality with 300-500 million cases annually. Our aims are not ends, but a means to achieve the following: Iterate the need for experimental biologists to (i) know how to design their customized oligos and (ii) have some idea about gene expression analysis and the need for cooperation between experimental biologists and their counterpart, the computational biologists. These will help experimental biologists to coordinate very well the front and the back ends of the system biology analysis of the whole genome effectively

The Anopheles gambiae Insecticidal Targets Made Bare by In-silica Analysis

seveml wot·ks had attempted to use genomics to explain the mode of mosquito t·esistance and pt·edict dmg tat·get. The use of insecticides in val'ious ways has been the majm· malal'ia vectot· conti'Ol stmtegy being deployed lately, mostly pyt·ethi'Oid, the majm· t·ecommended compound class fot· IRS, ITNs and LLITNs. Resistance to dmgs and insecticides has continually obstmcted vectm·/malal'ia contt·ol stntegies. The advet·t effect is so enonnous in the Sub-Sahamn Afl'ican; its socioeconomic impact is unquantifiable in evet·y measm·e. Thus, the quick necessity fm· the development and elucidation of potent, cheap and efficient new potential insecticidal tat·gets, especially those in the class pyt·ethi'Oid fm· the malal'ia vectot·, A. gambiae. In this wm·k, an updated Anopheles gambiae biochemical metabolic netwm·k (AnoCyc vel'l.O), othet·wise known as pathway genome database (PGDB) was extmcted, the database was t·econstt·ucted by developing a computational gmph model in an appi'Oach that modeled the metabolic netwot·k of the m·ganism as a bipat·tite gmph, deployed the concept of choke point, load point and t·eaction without deviation to detet·mine the essential enzymatic t·eactions in the netwm·ks. Each potential dmg tat·get to theit· coiTesponding gene/pi'Otein and such encoding pi'Otein sequences wet·e extmcted. (PDB) was blasted fot· genes that have stmctm·e m· homologue of >= 30 sequence identity. Finally, we deployed Ovet·ton and Bation Scm·e (OB-Scm·e) and Pat·Ct·ys pt·ediction to mnk pi'Oteins by theit' likely success in ct·ystallization. 61 potential insecticidal candidate tat·gets was made bat·e, one clinically validated insecticidal tat·get and othet·s with biological evidence in the litemtnt·e. Seven of these tat·gets ideally stand out and have no homology with othet· vetiebmtes. These in depth dissection of the biochemical metabolic netwm·ks of the Anopheles effectively identified the ideal gene pi'Oducts and specifically extmct essential enzymes as new potential insecticidal tat·get against A. gambiae

Comparative Analysis of Similarity Check Mechanism for Motif Extraction

In this work, a comparative analysis of the similarity check mechanism used in the most effective algorithm for mining simple motifs GEMS (Gene Enrichment Motif Searching) and that used in a popular multi-objective genetic algorithm, MOGAMOD (Multi-Objective Genetic Algorithm for Motif Discovery) was done. In our previous work, we had reported the implementation of GEMS on suffix tree –Suffix Tree Gene Enrichment Motif Searching (STGEMS) and shown the linear asymptotic runtime achieved. Here, we attempt to empirically proof the high sensitivity of the resulting algorithm, STGEMS in mining motifs from challenging sequences like we have in Plasmodium falciparum. The results obtained validates the high sensitivity of the similarity check mechanism employed in GEMS and also shows that a careful deployment of this mechanism in the multi-objective genetic algorithm, improved the sensiti

New Insights into the Genetic Regulation of Plasmodium Falciparum Obtained by Bayesian Modeling

The most fatal and prevalent form of malaria is caused by the bloodborne pathogen Plasmodium falciparum (henceforth P.f). Annually, approximately three million people died of malaria. Despite P.f devastivating effect globally, the vast majority of its proteins have not been characterized experimentally. In this work, we provide computational insight that explore the modalities of the regulation for some important group of genes of P.f, namely components of the glycolytic pathway, and those involved in apicoplast metabolism. Glycolysis is a crucial pathway in the maintenance of the parasite while the recently discovered apicoplast contains a range of metabolic pathways and housekeeping processes that differ radically to those of the host, which makes it ideal for drug therapy

In Silico Gene Regulatory Network of the Maurer’s Cleft Pathway in Plasmodium falciparum

The Maurer’s clefts (MCs) are very important for the survival of Plasmodium falciparum within an infected cell as they are induced by the parasite itself in the erythrocyte for protein trafficking. The MCs form an interesting part of the parasite’s biology as they shed more light on how the parasite remodels the erythrocyte leading to host pathogenesis and death. Here, we predicted and analyzed the genetic regulatory network of genes identified to belong to the MCs using regularized graphical Gaussian model. Our network shows four major activators, their corresponding target genes, and predicted binding sites. One of these master activators is the serine repeat antigen 5 (SERA5), predominantly expressed among the SERA multigene family of P. falciparum, which is one of the blood-stage malaria vaccine candidates. Our results provide more details about functional interactions and the regulation of the genes in the MCs’ pathway of P. falciparum

In Silico Gene Regulatory Network of the Maurer’s Cleft Pathway in Plasmodium falciparum

The Maurer’s clefts (MCs) are very important for the survival of Plasmodium falciparum within an infected cell as they are induced by the parasite itself in the erythrocyte for protein trafficking. The MCs form an interesting part of the parasite’s biology as they shed more light on how the parasite remodels the erythrocyte leading to host pathogenesis and death. Here, we predicted and analyzed the genetic regulatory network of genes identified to belong to the MCs using regularized graphical Gaussian model. Our network shows four major activators, their corresponding target genes, and predicted binding sites. One of these master activators is the serine repeat antigen 5 (SERA5), predominantly expressed among the SERA multigene family of P. falciparum, which is one of the blood-stage malaria vaccine candidates. Our results provide more details about functional interactions and the regulation of the genes in the MCs’ pathway of P. falciparum

Recent advances in functionalized quinoline scaffolds and hybrids—Exceptional pharmacophore in therapeutic medicine

Quinoline is one of the most common nitrogen-containing heterocycles owing to its fascinating pharmacological properties and synthetic value in organic and pharmaceutical chemistry. Functionalization of this moiety at different positions has allowed for varying pharmacological activities of its derivative. Several publications over the last few decades have specified various methods of synthesis. This includes classical methods of synthesizing the primary quinoline derivatives and efficient methods that reduce reaction time with increased yield employing procedures that fulfill one of the twelve green chemistry principles, “safer solvent”. The metal nanoparticle-catalyzed reaction also serves as a potent and effective technique for the synthesis of quinoline with excellent atom efficiency. The primary focus of this review is to highlight the routes to synthesizing functionalized quinoline derivatives, including hybrids that have moieties with predetermined activities bound to the quinoline moiety which are of interest in synthesizing drug candidates with dual modes of action, overcoming toxicity, and resistance amongst others. This was achieved using updated literature, stating the biological activities and mechanisms through which these compounds administer relief. The ADMET studies and Structure-Activity Relationship (SAR) of novel derivatives were also highlighted to explore the drug-likeness of the quinoline-hybrids and the influence of substituent characteristics and position on the biological activity of the compounds

Ensemble based Clustering of Plasmodium falciparum genes

Ensemble learning is a recent and extended approach to the unsupervised data mining technique called clustering which is used from finding natunl gmupings that exist in a dataset. Hetre, we applied an ensemble based clustering algol'ithm called Random Fot·ests with Pat·tition amund Medoids (PAM) to multiple time sel'ies gene expt·ession data of Plasmodium falcipat·um. The Random Fot·est algol'ithm is most common ensemble leat·ning appmach that uses decision tt·ees. Random Fm·est consists of lat·ge numbet· of classification tt·ees (nnging fmm hundt·eds to thousands) built from rabootstnp sampling of the dataset. We also applied the following intemal clustet· validity measures; Silhouette Width index, Connectivity Index and the Dunn Index to select the optimal numbet· of final clustet·s. Om· t·esults show that ensemble based clustering is indeed a good altet·native fm· clustet· analysis with the premise of an improved performance ovet· traditional clustering algorithm