Collaborative Mining of Whole Genome Sequences for Intelligent HIV-1 Sub-Strain(s) Discovery.

BACKGROUND: Effective global antiretroviral vaccines and therapeutic strategies depend on the diversity, evolution, and epidemiology of their various strains as well as their transmission and pathogenesis. Most viral disease-causing particles are clustered into a taxonomy of subtypes to suggest pointers toward nucleotide-specific vaccines or therapeutic applications of clinical significance sufficient for sequence-specific diagnosis and homologous viral studies. These are very useful to formulate predictors to induce cross-resistance to some retroviral control drugs being used across study areas. OBJECTIVE: This research proposed a collaborative framework of hybridized (Machine Learning and Natural Language Processing) techniques to discover hidden genome patterns and feature predictors for HIV-1 genome sequences mining. METHODS: 630 human HIV-1 genome sequences above 8500 bps were excavated from the National Center for Biotechnology Information (NCBI) database (https://www.ncbi.nlm.nih.gov) for 21 countries across different continents, except for Antarctica. These sequences were transformed and learned using a self-organizing map (SOM). To discriminate emerging/new sub-strain(s), the HIV-1 reference genome was included as part of the input isolates/samples during the training. After training the SOM, component planes defining pattern clusters of the input datasets were generated for cognitive knowledge mining and subsequent labeling of the datasets. Additional genome features, including dinucleotide transmission recurrences, codon recurrences, and mutation recurrences, were finally extracted from the raw genomes to construct output classification targets for supervised learning. RESULTS: SOM training explains the inherent pattern diversity of HIV-1 genomes as well as interand intra-country transmissions in which mobility might play an active role, as corroborated by the literature. Nine sub-strains were discovered after disassembling the SOM correlation hunting matrix space attributed to disparate clusters. Cognitive knowledge mining separated similar pattern clusters bounded by a certain degree of correlation range, as discovered by the SOM. Kruskal-Wallis ranksum test and Wilcoxon rank-sum test showed statistically significant variations in dinucleotide, codon, and mutation patterns. CONCLUSION: Results of the discovered sub-strains and response clusters visualizations corroborate the existing literature, with significant haplotype variations. The proposed framework would assist in the development of decision support systems for easy contact tracing, infectious disease surveillance, and studying the progressive evolution of the reference HIV-1 genome.

Processed HIV prognostic dataset for control experiments.

This paper provides a control dataset of processed prognostic indicators for analysing drug resistance in patients on antiretroviral therapy (ART). The dataset was locally sourced from health facilities in Akwa Ibom State of Nigeria, West Africa and contains 14 attributes with 1506 unique records filtered from 3168 individual treatment change episodes (TCEs). These attributes include sex, before and follow-up CD4 counts (BCD4, FCD4), before and follow-up viral load (BRNA, FRNA), drug type/combination (DTYPE), before and follow-up body weight (Bwt, Fwt), patient response to ART (PR), and classification targets (C1-C5). Five (5) output membership grades of a fuzzy inference system ranging from very high interaction to no interaction were constructed to model the influence of adverse drug reaction (ADR) and subsequently derive the PR attribute (a non-fuzzy variable). The PR attribute membership clusters derived from a universe of discourse table were then used to label the classification targets as follows: C1=no interaction, C2=very low interaction, C3=low interaction, C4=high interaction, and C5=very high interaction. The classification targets are useful for building classification models and for detecting patients with ADR. This data can be exploited for the development of expert systems, for useful decision support to treatment failure classification [1] and effectual drug regimen prescription.

Fuzzy-multidimensional deep learning for efficient prediction of patient response to antiretroviral therapy.

Drug component interactions are most likely to trigger unexpected pharmacological effects with unknown causal mechanisms, hence, demanding the discovery of patterns to establish suitable and effective regimens. This paper proposes a novel framework that embeds machine learning (ML) and multidimensional scaling (MDS) techniques, for efficient prediction of patient response to antiretroviral therapy (ART). To achieve this, experiment databases were created from two independent sources: a publicly available HIV domain datasets of patients with failed treatment - hosted by the Stanford University, hereinafter referred to as the Stanford HIV database, and locally sourced datasets gathered from 13 prominent healthcare facilities treating HIV patients in Akwa Ibom State of Nigeria, hereinafter referred to as the Akwa-Ibom HIV database: with 5,780 and 3,168 individual treatment change episodes (TCEs) of HIV treatment indicators (baseline CD4 count (BCD4), followup CD4 count (FCD4), baseline viral load (BRNA), followup viral load (FRNA), and drug type combination (DType)), observed from 1,521 and 1,301 unique patient records, respectively. A hybridised (two-stage) classification system consuming the Interval Type-2 Fuzzy Logic (IT2FL) and Deep Neural Network (DNN) was employed to model and optimise patients' response to ART with appreciable error pruning achieved through MDS. Visualisation of the experiment databases showed remarkable immunological changes in the Akwa-Ibom HIV database, as the FCD4 of TCEs clustered far above the BCD4, compared to the Stanford HIV database, where over 40% of FCD4 clustered below the BCD4. Similar changes were noticed for the RNA, as more FRNA copies clustered below the BRNA for the Akwa-Ibom datasets, compared to the Stamford datasets. DNN classification results for both databases showed best performance metrics for the Levenberg-Marquardt algorithm when compared with the resilient backpropagation algorithm, with improved drug pattern predictions for experiment with MDS. This paper is most likely to evolve an avenue that triggers interesting combination(s) for optimum patient response, while ensuring minimal side effects, as further findings revealed the superiority of the proposed approach over existing approaches.