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Islam, M.

Publications and source records attributed to Islam, M..

49 records · Page 3Linked to original sources

PanClassif: Improving pan cancer classification of single cell RNA-seq using machine learning

Cancer is one of the major causes of human death per year. In recent years, cancer identification and classification using machine learning have gained momentum due to the availability of high throughput sequencing data. Using RNA-seq, cancer research is blooming day by day and new insights of cancer and related treatments are coming into light. In this paper, we propose PanClassif, a method that requires a very few and effective genes to detect cancer from RNA-seq data and is able to provide performance gain in several wide range machine learning classifiers. We have taken 22 types of cancer samples from The Cancer Genome Atlas (TCGA) having 8287 cancer samples and 680 normal samples. Firstly, PanClassif uses k-Nearest Neighbor (k-NN) smoothing to smooth the samples to handle noise in the data. Then effective genes are selected by Anova based test. For balancing the train data, PanClassif applies an oversampling method, SMOTE. We have performed comprehensive experiments on the datasets using several classification algorithms. Experimental results shows that PanClassif out-perform existing state-of-the-art methods available and shows consistent performance for two single cell RNA-seq datasets taken from Gene Expression Omnibus (GEO). PanClassif improves performances of a wide variety of classifiers for both binary cancer prediction and multi-class cancer classification. PanClassif is available as a python package (https://pypi.org/project/panclassif/). All the source code and materials of PanClassif are available at https://github.com/Zwei-inc/panclassif.

bioinformatics↗

Concept design of a bionic grasp to capture the hand motion

This study has focused on designing a device allowing the user to perform hand exercise motions, in relation with previous methods with good effects in stroke rehabilitation. The project is mainly aimed at designing a low cost, easy to handle and easy to manufacture smart glove to assist users with finger flexion and extensions, which can at the same time transfer data to an application. The methodology used here includes research, design, simulation testing and finalised design. It started with research and investigations on the needs of the users and previous efficient stroke rehabilitation methods. This has been followed with 4 concept designs, which has been tested and evaluated in the next stage for possible optimizations using a computer modelling technique. At the final step, the virtual prototype and product design specification (PDS) of the finalise concept for the interactive device has been illustrated.

bioengineering↗

ASSOCIATION STUDY OF SIX CANDIDATE GENES WITH MAJOR DEPRESSIVE DISORDER IN THE NORTH-WESTERN POPULATION OF PAKISTAN

People around the world are currently affected by Major Depressive Disorder (MDD). Despite its many aspects, symptoms, manifestations and impacts, efforts have been made to identify the root causes of the disorder. In particular, genetic studies have concentrated on identifying candidate genes for MDD and exploring associations between these genes and some specific group of individuals. The aim of this research was to find out the association between single nucleotide polymorphisms in 6 candidate genes linked to the neurobiology of major depressive disorder in the North-Western population of Pakistan. We performed a case-control analysis, with 400 MDD and 232 controls. A trained psychiatrist or clinical psychologists evaluated the patients. Six polymorphisms were genotyped and tested for allele and genotype association with MDD. There were no statistical variations between MDD patients and healthy controls for genotypic and allelic distribution of all the polymorphisms observed. Thus, our analysis does not support the major role of these polymorphisms in contributing to MDD susceptibility, although it does not preclude minor impact. The statistically significant correlation between six polymorphisms and major depressive disorder in the studied population was not observed. There are inconsistencies in investigations around the world. Future research, including GWAS and association analysis on larger scale should be addressed for further validation and replication of the present findings.

genetics↗

Molecular characterization of vancomycin-resistant Enterococcus faecium isolates collected from the Dallas, Texas area

Vancomycin-resistant E. faecium (VREfm) is a significant public health concern because of limited treatment options. Genomic surveillance can be used to monitor VREfm transmission and evolution. Genomic analysis of VREfm has not been reported for the Dallas/Fort Worth/Arlington, Texas, area, which is currently the 4th largest metropolitan area in the United States. Our study aimed to address this gap in knowledge by analyzing the genomes of 46 VREfm and one vancomycin-sensitive comparator collected during routine fecal surveillance of high-risk patients upon admission to a Dallas, Texas hospital system (August to October, 2015). 31 complete and 16 draft genome sequences were generated. The closed VREfm genomes possessed up to 12 extrachromosomal elements each. Overall, 251 closed putative plasmid sequences assigned to previously described and newly defined rep family types were obtained. Phylogenetic analysis identified 10 different sequence types (STs) among the isolates, with the most prevalent being ST17 and ST18. Strikingly, all but three of the VREfm isolates encoded vanA-type vancomycin resistance within Tn1546- like elements on a pRUM-like (rep17) plasmid backbone. Relative to a previously reported typing scheme for the vanA-encoding Tn1546, new variants of the Tn1546 were identified that harbored a combination of 7 insertion sequences (IS), including 3 novel IS elements reported in this study (ISEfa16, ISEfa17 and ISEfa18). We conclude that pRUM-like plasmids are important vectors for vancomycin resistance in the Dallas, Texas area and should be a focus of plasmid surveillance efforts. ImportanceVancomycin is an antibiotic used to treat infections caused by multidrug-resistant Gram-positive bacteria. Vancomycin resistance is common in clinical isolates of the Gram-positive pathogen Enterococcus faecium. In E. faecium, vancomycin resistance genes can be disseminated by plasmids with different host ranges and transfer efficiencies. Surveillance of resistance plasmids is critical to understanding antibiotic resistance transmission. This study analyzed the genome sequences of VREfm collected from the Dallas, Texas area, with particular focus on the mobile elements associated with vancomycin resistance genes. We find that a single plasmid family, the pRUM-like family, is associated with vancomycin resistance in the majority of isolates sampled. Our work suggests that the pRUM-like plasmids should continue to be studied to understand their mechanisms of maintenance, transmission, and evolution in VREfm.

microbiology↗

Detour learning ability and the effect of novel sensory cues on learning in Australian bull ants, Myrmecia midas

Many animals navigate in a structurally complex environment which requires them to detour around physical barriers that they encounter. While many studies in animal cognition suggest that they are able to adeptly avoid obstacles, it is unclear whether a new route is learned to navigate around these barriers and, if so, what sensory information may be used to do so. We investigated detour learning ability in the Australian bull ant, Myrmecia midas, which primarily uses visual landmarks to navigate. We first placed a barrier on the ants natural path of their foraging tree. Initially, 46% of foragers were unsuccessful in detouring the obstacle. In subsequent trips, the ants became more successful and established a new route. We observed up to eight successful foraging trips detouring around the barrier. When we subsequently changed the position of the barrier, made a new gap in the middle of the obstacle, or removed the barrier altogether, ants mostly maintained their learned motor routine, detouring with a similar path as before, suggesting that foragers were not relying on barrier cues and therefore learned a new route around the obstacle. In additional trials, when foragers encountered new olfactory or tactile cues, or the visual environment was blocked, their navigation was profoundly disrupted. These results suggest that changing sensory information, even in modalities that foragers do not usually need for navigation, drastically affects the foragers ability to successful navigate. Subject CategoryNeuroscience and Cognition

animal behavior and cognition↗

Comprehensive studies of Head Maralla, Punjab, Pakistan vegetation for ethnopharmacological and ethnobotanical uses and their elaboration through quantitative indices

Head Maralla is a non-recognized wetland with diversified flora that becomes focus of current studies. Whole plant or their parts are being used for treating various maladies and they are the integral part of livelihood in the area. Unique species including Osmunda regalis is used for blood and renal diseases purifier. Wild plant resources are key to traditional ethnobotanical knowledge based practices and industrial applications. Current study reports Head Marala inhabitants interaction with these resources and identify priorities at species and habitat level for conservation. Four sites viz., River Tavi, Upstream Chenab, River Manawarwala Tavi and Bhalolpur were designated to record traditional knowledge through questionnaire and interviews during field trips. One hundred nineteen (119) plant species were identified belonging to 54 families, of which 87 species were of dicot, 12monocots, 05ferns, and 4 species of bryophytes. Fifty percent of the plant species were utilized as a whole for therapeutic purposes, followed by leaves which had more than 20% usage of total consumption. Ailments viz., urination (14%) followed by cough (8%), cold (7%), stomach (6%), asthma (6%), constipation (5%), laxative (5%), diarrhea (4%) etc., were associated with vegetation. Bronchial disorders, pneumonia, dyspepsia, anthelmintic and kidney stones, etc., were also among other diseases commonly cured by traditional knowledge. Fifteen percent of vegetation contributes as fodder species consumed by local community for livestock while almost 17% of local plants were utilized for industrial purposes like timber, fuel, furniture, wooden pots and sports goods. In conclusion the ecosystem of Head Maralla is a complex of aquatic, terrestrial and agricultural land that is located on climatic and geographical divides, which further add to botanical interest as included many wetland habitats with unique diversity of plants. It is suggested to devise comprehensive conservation strategies to safe indigenous knowledge in systematic way for comprehending ecological services.

plant biology↗

Agro-morphological, yield, and genotyping-by-sequencing data of selected wheat germplasm

Wheat (Triticum aestivum) is the most important staple food in Pakistan. Knowledge of its genetic diversity is critical for designing effective crop breeding programs. Here we report agro-morphological and yield data for 112 genotypes (including 7 duplicates) of wheat (Triticum aestivum) cultivars, advance lines, landraces and wild relatives, collected from several research institutes and breeders across Pakistan. We also report genotyping-by-sequencing (GBS) data for a selected sub-set of 52 genotypes. Sequencing was performed using Illumina HiSeq 2500 platform using the PE150 run. Data generated per sample ranged from 1.01 to 2.5 Gb; 90% of the short reads exhibited quality scores above 99.9%. TGACv1 wheat genome was used as a reference to map short reads from individual genotypes and to filter single nucleotide polymorphic loci (SNPs). On average, 364,074{+/-}54479 SNPs per genotype were recorded. The sequencing data has been submitted to the SRA database of NCBI (accession number SRP179096). The agro-morphological and yield data, along with the sequence data and SNPs will be invaluable resources for wheat breeding programs in future.

genetics↗

Activation of SnRK2 by the Raf-like kinase ARK represents a common mechanism of ABA response in embryophytes

The Raf-like protein kinase ARK previously identified in the moss Physcomitrella patens acts as an upstream regulator of subgroup III SnRK2, the key regulator of abscisic acid (ABA) and abiotic stress responses. However, the mechanisms underlying activation of ARK by ABA and abiotic stress for the regulation of SnRK2 including the role of ABA receptor-associated group A PP2C (PP2C-A) are not understood. We identified Ser1029 as the phosphorylation site in the activation loop of ARK, which provided a possible mechanism for regulation of its activity. Analysis of transgenic ark lines expressing ARK-GFP with Ser1029-to-Ala mutation indicated that this replacement causes reductions in ABA-induced gene expression, stress tolerance and SnRK2 activity. Immunoblot analysis using an anti-phosphopeptide antibody indicated that ABA treatments rapidly stimulate Ser1029 phosphorylation in wild type. The phosphorylation profile of Ser1029 in ABA-hypersensitive ppabi1 lacking PP2C-A was similar to that in wild type, whereas little Ser1029 phosphorylation was observed in ABA-insensitive ark missense lines. Furthermore, newly isolated ppabi1 ark lines showed ABA-insensitive phenotypes similar to those of ark lines. These results indicate that ARK is a primary activator of SnRK2, preceding negative regulation by PP2C-A in bryophytes, which provides a prototypal mechanism for ABA and abiotic stress-responses in embryophytes. One sentence summaryPhysiological characterization of various moss mutants revealed a common mechanism for phytohormone responses under water deficit in all land plants.

plant biology↗

Complete chloroplast genomes of Anthurium huixtlense and Pothos scandens (Pothoideae, Araceae): unique inverted repeat expansion and contraction affect rate of evolution

The subfamily Pothoideae belongs to the ecologically important plant family Araceae. Here, we report the chloroplast genomes of two species of the subfamily Pothoideae: Anthurium huixtlense (163,116 bp) and Pothos scandens (164,719 bp). The chloroplast genome of P. scandens showed unique inverted repeats (IRs) contraction and expansion, which increases the size of the large single copy (102,956) region and decreases the size of the small single-copy (6779 bp) region. This led to duplication of many single-copy genes due to transfer to IR regions from the small single-copy (SSC) region, whereas some duplicate genes became single copy due to transfer to large single-copy regions. The rate of evolution of protein-coding genes was affected by the contraction and expansion of IRs; we found higher mutation rates for genes that exist in single-copy regions as opposed to IRs. We found a 2.3-fold increase of oligonucleotide repeats in P. scandens when compared with A. huixtlense, whereas amino acid frequency and codon usage revealed similarities. We recorded higher transition substitutions than transversion substitutions. The transition/transversion ratio was 2.26 in P. scandens and 2.12 in A. huixtlense. We also found a higher rate of transversion substitutions linked with non-synonymous substitutions than synonymous substitutions. The phylogenetic inference of the limited species showed the monophyly of the Araceae subfamilies. Our study provides insight into the molecular evolution of chloroplast genomes in the subfamily Pothoideae and family Araceae.

genomics↗

STELAR: A statistically consistent coalescent-based species tree estimation method by maximizing triplet consistency

BackgroundSpecies tree estimation is frequently based on phylogenomic approaches that use multiple genes from throughout the genome. However, estimating a species tree from a collection of gene trees can be complicated due to the presence of gene tree incongruence resulting from incomplete lineage sorting (ILS), which is modelled by the multi-species coalescent process. Maximum likelihood and Bayesian MCMC methods can potentially result in accurate trees, but they do not scale well to large datasets.\n\nResultsWe present STELAR (Species Tree Estimation by maximizing tripLet AgReement), a new fast and highly accurate statistically consistent coalescent-based method for estimating species trees from a collection of gene trees. We formalized the constrained triplet consensus (CTC) problem and showed that the solution to the CTC problem is a statistically consistent estimate of the species tree under the multi-species coalescent (MSC) model. STELAR is an efficient dynamic programming based solution to the CTC problem which is highly accurate and scalable. We evaluated the accuracy of STELAR in comparison with SuperTriplets, which is an alternate fast and highly accurate triplet-based supertree method, and with MP-EST and ASTRAL - two of the most popular and accurate coalescent-based methods. Experimental results suggest that STELAR matches the accuracy of ASTRAL and improves on MP-EST and SuperTriplets.\n\nConclusionsTheoretical and empirical results (on both simulated and real biological datasets) suggest that STELAR is a valuable technique for species tree estimation from gene tree distributions.

bioinformatics↗

Unbiased metagenomic sequencing for pediatric meningitis in Bangladesh reveals neuroinvasive Chikungunya virus outbreak and other unrealized pathogens

The disease burden due to meningitis in low and middle-income countries remains significant and failure to determine an etiology impedes appropriate treatment for patients and evidence-based policy decisions for populations. Broad-range pathogen surveillance using metagenomic next-generation sequencing (mNGS) of RNA isolated from cerebral spinal fluid (CSF) provides an unbiased assessment for possible infectious etiologies. In this study, our objective was to use mNGS to identify etiologies of pediatric meningitis in Bangladesh.\n\nWe conducted a retrospective case-control mNGS study on CSF from patients with known neurologic infections (n=36), idiopathic meningitis (n=25), without infection (n=30) and six environmental samples collected between 2012-2018. Using an open-access, cloud-based bioinformatics pipeline (IDseq) and machine learning, we identified potential pathogens which were confirmed through qPCR and Sanger sequencing. These cases were followed-up through phone/home-visits. The CSF samples were collected from children with WHO-defined meningeal signs during prospective meningitis surveillance at the largest pediatric referral hospital in Bangladesh.\n\nThe 91 participants (42% female) ranged in age from 0-160 months (median: 9 months). In samples with known infectious causes of meningitis and without infections (n=66), there was 83% concordance between mNGS and conventional testing. In idiopathic cases (n=25), mNGS identified a potential etiology in 40% (n=10), including bacterial and viral pathogens. There were three instances of neuroinvasive Chikungunya virus (CHIKV). The CHIKV genomes were >99% identical to each other and to a Bangladeshi strain only previously recognized to cause systemic illness in 2017. CHIKV qPCR of all remaining stored CSF samples from children who presented with idiopathic meningitis in 2017 at the same hospital (n=472) revealed 17 additional CHIKV meningitis cases. Orthogonal molecular confirmation of each mNGS-identified infection, case-based clinical data, and follow-up of patients substantiated the key findings.\n\nUsing mNGS, we obtained a microbiological diagnosis for 40% of idiopathic meningitis cases and identified a previous unappreciated pediatric CHIKV meningitis outbreak. Case-control CSF mNGS surveys can complement conventional diagnostic methods to identify etiologies of meningitis and facilitate informed policy decisions.

genomics↗

WRN Helicase is a Synthetic Lethal Target in Microsatellite Unstable Cancers

Summary paragraphSynthetic lethality, an interaction whereby the co-occurrence of two or more genetic events lead to cell death but one event alone does not, can be exploited to develop novel cancer therapeutics1. DNA repair processes represent attractive synthetic lethal targets since many cancers exhibit an impaired DNA repair pathway, which can lead these cells to become dependent on specific repair proteins2. The success of poly (ADP-ribose) polymerase 1 (PARP-1) inhibitors in homologous recombination-deficient cancers highlights the potential of this approach in clinical oncology3,4. Hypothesizing that other DNA repair defects would give rise to alternative synthetic lethal relationships, we asked if there are specific dependencies in cancers with microsatellite instability (MSI), which results from impaired DNA mismatch repair (MMR). Here we analyzed data from large-scale CRISPR/Cas9 knockout and RNA interference (RNAi) silencing screens and found that the RecQ DNA helicase WRN was selectively essential in MSI cell lines, yet dispensable in microsatellite stable (MSS) cell lines. WRN depletion induced double-strand DNA breaks and promoted apoptosis and cell cycle arrest selectively in MSI models. MSI cancer models specifically required the helicase activity, but not the exonuclease activity of WRN. These findings expose WRN as a synthetic lethal vulnerability and promising drug target in MSI cancers.

cancer biology↗

Factors mediating synergism between vancomycin and chlorhexidine in VanA-type vancomycin-resistant Enterococcus faecium

Vancomycin-resistant enterococci (VRE) are important nosocomial pathogens that cause life-threatening infections. To control hospital-associated infections, skin antisepsis and bathing utilizing chlorhexidine is recommended for VRE patients in acute care hospitals. Previously, we reported that exposure to inhibitory chlorhexidine levels induced the expression of vancomycin resistance genes in VanA-type Enterococcus faecium. However, vancomycin susceptibility actually increased for VanA-type E. faecium in the presence of chlorhexidine. Hence, a synergistic effect of the two antimicrobials was observed. In this study, we used multiple approaches to investigate the mechanism of synergism between chlorhexidine and vancomycin in the VanA-type VRE strain E. faecium 1,231,410. We generated clean deletions of 7 of 11 pbp, transpeptidase, and carboxypeptidase genes in this strain (ponA, pbpF, pbpZ, pbpA, ddcP, ldtfm, and vanY). Deletion of ddcP, encoding a membrane-bound carboxypeptidase, altered the synergism phenotype. Furthermore, using in vitro evolution, we isolated a spontaneous synergy escaper mutant and utilized whole genome sequencing to determine that a mutation in pstB, encoding an ATPase of phosphate-specific transporters, also altered synergism. Finally, addition of excess D-lactate, but not D-alanine, enhanced synergism. Overall, our work identified factors that alter chlorhexidine-induced vancomycin resensitization in a model VanA-type VRE strain.

microbiology↗