Biology subjects

Mishra, A.

Publications and source records attributed to Mishra, A..

At least 127 records · Page 7Linked to original sources

bioRxiv2021

Ubiquitination is essential for recovery of cellular activities followingheat shock

Eukaryotic cells respond to stress via adaptive programs that include reversible shutdown of key cellular processes, the formation of stress granules, and a global increase in ubiquitination. The primary function of this ubiquitination is generally considered to be tagging damaged or misfolded proteins for degradation. Here we show that different types of stress generate distinct ubiquitination patterns. For heat stress, ubiquitination correlates with cellular activities that are downregulated during stress, including nucleocytoplasmic transport and translation, as well as with stress granule constituents. Ubiquitination is not required for the shutdown of these processes or for stress granule formation, but is essential for resumption of cellular activities and for stress granule disassembly. These findings indicate that stress-induced ubiquitination primes the cell for recovery following heat stress. One Sentence SummaryStress-induced ubiquitination is essential for recovery of cellular activities following heat stress.

cell biology↗

bioRxiv2021

Enhancing neuronal plasticity through intracranial theta burst stimulation in the human sensorimotor cortex.

The progress of therapeutic neuromodulation greatly depends on improving stimulation parameters to most efficiently induce neuroplasticity effects. Intermittent Theta Burst stimulation (iTBS), a form of electrical stimulation that mimics the natural brain activity patterns, has shown efficacy in inducing such effects in animal studies and rhythmic Transcranial Magnetic Stimulation (rTMS) studies in humans. However, little is known about the potential neuroplasticity effects of iTBS applied through intracranial electrodes in humans which could have implications for deep brain stimulation therapies. This study characterizes the physiological effects of cortical iTBS in the human cortex and compare them with single pulse alpha stimulation, another frequently used paradigm in rTMS research. We applied these stimulation paradigms to well-defined regions in the sensorimotor cortex which elicited contralateral hand or arm muscle contractions during electrical stimulation mapping in epilepsy patients implanted with intracranial electrodes. Treatment effects were evaluated using effective connectivity and beta oscillations coherence measures in areas connected to the treatment site as defined with cortico-cortical evoked potentials. Our results show that iTBS increases beta band synchronization within the sensorimotor network indicating a potential neuroplasticity effect. The effect is specific to the sensorimotor system, the beta frequency band and the stimulation pattern (no effect was found with single-pulse alpha stimulation). The effects outlasted the stimulation by three minutes. By characterizing the neurophysiological effects of iTBS within well-defined cortical networks, we hope to provide an electrophysiological framework that allows clinicians and researchers to optimize brain stimulation protocols which may have translational value.

neuroscience↗

bioRxiv2021

Desiccation stress acts as cause as well as cost of dispersal in Drosophila melanogaster

O_LIEnvironmental stress is one of the important causes of biological dispersal. At the same time, the process of dispersal itself can incur and/or increase susceptibility to stress for the dispersing individuals. Therefore, in principle, stress can serve as both a cause and a cost of dispersal. C_LIO_LIDesiccation stress is an environmentally relevant stress faced by many organisms, known to shape their population dynamics and distribution. However, the potentially contrasting roles of desiccation stress as a cause and a cost of dispersal have not been investigated. Furthermore, while desiccation stress often affects organisms in a sex-biased manner, it is not known whether the desiccation-dispersal relationship varies between males and females. C_LIO_LIWe studied the role of desiccation stress as a cause and cost of dispersal in a series of experiments using D. melanogaster adults in two-patch dispersal setups. We were interested in knowing whether (a) dispersers are the individuals that are more susceptible to desiccation stress, (b) dispersers pay a cost in terms of reduced resistance to desiccation stress, (c) dispersal evolution alters the desiccation cost of dispersal, and (d) females pay a reproductive cost of dispersal. For this, we modulated the degree of desiccation stress faced by the flies as well as the provision of rest following a dispersal event. C_LIO_LIOur data showed that desiccation stress served as a significant cause of dispersal in both sexes. Further investigation revealed an increase in both male and female dispersal propensity with increasing desiccation duration. Next, we found a male-biased cost of dispersal in terms of reduced desiccation resistance. This trend was preserved in dispersal-selected and non-selected controls as well, where the desiccation cost of dispersal in females was very low compared to the males. Finally, we found that the females instead paid a significant reproductive cost of dispersal. C_LIO_LIOur results highlight the complex relationship between desiccation stress and dispersal, whereby desiccation resistance can show both a positive and a negative association with dispersal. Furthermore, the sex differences observed in these trait associations may translate into differences in movement patterns, thereby giving rise to sex-biased dispersal. C_LI

ecology↗

bioRxiv2021

A mechanistic model captures the emergence and implications of non-genetic heterogeneity and reversible drug resistance in ER+ breast cancer cells

Resistance to anti-estrogen therapy is an unsolved clinical challenge in successfully treating ER+ breast cancer patients. Acquisition of mutations can confer heritable resistance to cancer cells, enabling their clonal selection to establish a drug-resistant population. Recent studies have demonstrated that cells can tolerate drug treatment without any genetic alterations too; however, the mechanisms and dynamics of such non-genetic adaptation remain elusive. Here, we investigate coupled dynamics of epithelial-mesenchymal transition (EMT) in breast cancer cells and emergence of reversible drug resistance. Our mechanism-based model for the underlying regulatory network reveals that these two axes can drive one another, thus conferring bidirectional plasticity. This network can also enable non-genetic heterogeneity in a population of cells by allowing for six co-existing phenotypes: epithelial-sensitive, mesenchymal-resistant, hybrid E/M-sensitive, hybrid E/M-resistant, mesenchymal-sensitive and epithelial-resistant, with the first two ones being most dominant. Next, in a population dynamics framework, we exemplify the implications of phenotypic plasticity (both drug-induced and intrinsic stochastic switching) and/or non-genetic heterogeneity in promoting population survival in a mixture of sensitive and resistant cells, even in the absence of any cell-cell cooperation. Finally, we propose the potential therapeutic use of MET (mesenchymal-epithelial transition) inducers besides canonical anti-estrogen therapy to limit the emergence of reversible drug resistance. Our results offer mechanistic insights into empirical observations on EMT and drug resistance and illustrate how such dynamical insights can be exploited for better therapeutic designs.

cancer biology↗

bioRxiv2021

Baseline cell proliferation rates and response to UV differ in Lymphoblastoid Cell Lines derived from healthy individuals of extreme constitution types

Differences in human phenotypes and susceptibility to complex diseases are an outcome of genetic and environmental interactions. This is evident in diseases that progress through a common set of intermediate patho-endophenotypes. Precision medicine aims to delineate the molecular players for individualized and early interventions. Functional studies in Lymphoblastoid Cell Line (LCL) model of phenotypically well characterized healthy individuals can help deconvolute and validate these molecular mechanisms. We developed LCLs from eight healthy individuals belonging to three extreme constitution types, deep phenotyped on the basis of Ayurveda. LCLs were characterized by karyotyping and immunophenotyping. Growth characteristics and response to UV was studied in these LCLs. We observed significant differences in cell proliferation rates between the contrasting groups such that one type (Kapha) proliferates significantly slower than the other two (Vata, Pitta). In response to UV, one fast growing group (Vata) shows higher cell death but recovers its numbers due to inherent higher rates of proliferation. The baseline differences in cell proliferation are key to understanding the survival of cells in UV stress. Variability in baseline cellular phenotypes not only explains the cellular basis of different constitutions types but can also help set priors during designing an individualized therapy with DNA damaging agents. This is the first study of its kind that shows variability of intermediate patho-phenotypes amongst healthy individuals that have implications in precision medicine.

cell biology↗

bioRxiv2020

Differential integrin adhesome expression defines human natural killer cell residency and developmental stage

Natural killer (NK) cells are innate immune cells that reside within tissue and circulate in peripheral blood. As such, they interact with a variety of complex microenvironments, yet how NK cells engage with these varied microenvironments is not well documented. The integrin adhesome represents a molecular network of defined and predicted integrin-mediated signaling interactions. Here, we define the integrin adhesome expression profile of NK cells from tonsil, peripheral blood and those derived from hematopoietic precursors through stromal cell coculture systems. We report that the site of cell isolation and NK cell developmental stage dictate differences in expression of adhesome associated genes and proteins. Furthermore, we define differences in cortical actin content associated with differential expression of actin regulating proteins, suggesting that differences in adhesome expression are associated with differences in cortical actin homeostasis. Together, these data provide new understanding into the diversity of human NK cell populations and how they engage with their microenvironment.

cell biology↗

bioRxiv2020

Retinoic acid Inducible Gene-I like Receptors Activate Snail and Slug to Limit RNA Viral Infections

RLRs sense cytosolic non-self RNAs including viral RNAs before mounting a response leading to the activation of Type-I IFNs. Here, we identify a previously unknown regulation of Snail, a transcription regulator known in EMT, during RNA viral infections and describe its possible implication. RNA viral infections, poly (I:C) transfection and ectopic expression of RLR components activated Snail and Slug in epithelial cells. Detailed examination revealed that MAVS and phosphorylated IRF3 are essential in this regulation. We identified two ISREs in SNAI1 promoter region and their alterations rendered the promoter non-responsive to phospho-IRF3 in luciferase assay. Ectopic expression of Snail and Slug activated RLR pathway and dramatically limited RNA viral infections in epithelial cells pointing to their antiviral functions. Thus, Snail and Slug are transcriptionally regulated by RLRs in a similar manner as IFN-{beta} and they in turn promote RLR pathway possibly strengthening the antiviral state in the cell.

immunology↗

bioRxiv2020

Perilipin2 down-regulation in beta cells impairs insulin secretion under nutritional stress and damages mitochondria

Perilipin 2 (PLIN2) is the lipid droplet (LD) protein in {beta} cells that increases under nutritional stress. Down-regulation of PLIN2 is often sufficient to reduce LD accumulation. To determine whether PLIN2 positively or negatively affects {beta} cell function under nutritional stress, PLIN2 was down-regulated in mouse {beta} cells, INS1 cells, and human islet cells. {beta} cell specific deletion of PLIN2 in mice on a high fat diet reduced glucose-stimulated insulin secretion (GSIS) in vivo and in vitro. Down-regulation of PLIN2 in INS1 cells blunted GSIS after 24 h incubation with 0.2 mM palmitic acids. Down-regulation of PLIN2 in human pseudoislets cultured at 5.6 mM glucose impaired both phases of GSIS, indicating that PLIN2 is critical for GSIS. Down-regulation of PLIN2 decreased specific OXPHOS proteins in all three models and reduced oxygen consumption rates in INS1 cells and mouse islets. Moreover, we found that PLIN2 deficient INS1 cells increased the distribution of a fluorescent oleic acid analog to mitochondria and showed signs of mitochondrial stress as indicated by susceptibility to fragmentation and alterations of acyl-carnitines and glucose metabolites. Collectively, PLIN2 in {beta} cells have an important role in preserving insulin secretion, {beta} cell metabolism and mitochondrial function under nutritional stress.

molecular biology↗

bioRxiv2020

Host immune responses after suprachoroidal delivery of AAV8 in nonhuman primate eyes

The suprachoroid is a potential space located between the sclera and choroid of the eye which provides a novel route for ocular drug or viral vector delivery. Suprachoroidal injection of AAV8 using transscleral microneedles enables widespread transgene expression in eyes of nonhuman primates, but may cause intraocular inflammation. We characterized the host humoral and cellular immune responses after suprachoroidal delivery of AAV8 expressing green fluorescent protein (GFP) in rhesus macaques, and found that it can induce a mild chorioretinitis that resolves after systemic corticosteroid administration, with recovery of photoreceptor morphology but persistent immune cell infiltration after 3 months. Suprachoroidal AAV8 triggered B-cell and T-cell responses against GFP, but only mild antibody responses to the viral capsid as compared to intravitreal injections of the same vector and dose. Systemic biodistribution studies showed lower AAV8 levels in liver and spleen after suprachoroidal injection compared with intravitreal delivery. Our findings suggest that suprachoroidal AAV8 primarily triggers host immune responses to GFP, likely due to sustained transgene expression in scleral fibroblasts outside the blood-retinal barrier, but elicits less humoral immune reactivity to the viral capsid than intravitreal delivery due to lower egress into systemic circulation. Thus, suprachoroidal AAV delivery of human transgenes may have significant translational potential for retinal gene therapy.

genetics↗

bioRxiv2020

In vivo and in vitro mechanistic characterization of a clinically relevant PolγA mutation

Mutations in POLG, encoding POL{gamma}A, the catalytic subunit of the mitochondrial DNA polymerase, cause a spectrum of disorders characterized by mtDNA instability. However, the molecular pathogenesis of POLG-related diseases is poorly understood and efficient treatments are missing. Here, we generated a POLGA449T/A449T mouse model, which reproduces the most common human recessive mutation of POLG, encoding the A467T change, and dissected the mechanisms underlying pathogenicity. We show that the A449T mutation impairs DNA binding and mtDNA synthesis activities of POL{gamma} in vivo and in vitro. Interestingly, the A467T mutation also strongly impairs interactions with POL{gamma}B, the homodimeric accessory subunit of holo-POL{gamma}. This allows the free POL{gamma}A to become a substrate for LONP1 protease degradation, leading to dramatically reduced levels of POL{gamma}A, which in turn exacerbates the molecular phenotypes of PolgA449T/A449T mice. Importantly, we validated this mechanism for other mutations affecting the interaction between the two POL{gamma} subunits. We suggest that LONP1 dependent degradation of POL{gamma}A can be exploited as a target for the development of future therapies.

genetics↗

bioRxiv2020

Dynamics of neural microstates in the VTA-striatal-prefrontal loop during novelty exploration in the rat

EEG microstates refer to quasi-stable spatial patterns of scalp potentials, and their dynamics have been linked to cognitive and behavioral states. Neural activity at single and multiunit levels also exhibit spatiotemporal coordination, but this spatial scale is difficult to relate to EEG. Here, we translated EEG microstate analysis to triple-area local field potential (LFP) recordings from up to 192 electrodes in rats to investigate the mesoscopic dynamics of neural microstates within and across brain regions. We performed simultaneous recordings from the prefrontal cortex (PFC), striatum (STR), and ventral tegmental area (VTA) during awake behavior (object novelty and exploration). We found that the LFP data can be accounted for by multiple, recurring, quasi-stable spatial activity patterns with an average period of stability of ~60-100 ms. The top four maps accounted for 60-80% of the total variance, compared to ~25% for shuffled data. Cross-correlation of the microstate time-series across brain regions revealed rhythmic patterns of microstate activations, which we interpret as a novel indicator of inter-regional, mesoscale synchronization. Furthermore, microstate features, and patterns of temporal correlations across microstates, were modulated by behavioural states such as movement and novel object exploration. These results support the existence of a functional mesoscopic organization across multiple brain areas, and open up the opportunity to investigate their relation to EEG microstates, of particular interest to the human research community. Significance StatementThe coordination of neural activity across the entire brain has remained elusive. Here we combine large-scale neural recordings at fine spatial resolution with the analysis of microstates, i.e. short-lived, recurring spatial patterns of neural activity. We demonstrate that the local activity in different brain areas can be accounted for by only a few microstates per region. These microstates exhibited temporal dynamics that were correlated across regions in rhythmic patterns. We demonstrate that these microstates are linked to behavior and exhibit different properties in the frequency domain during different behavioural states. In summary, LFP microstates provide an insightful approach to studying both mesoscopic and large-scale brain activation within and across regions.

neuroscience↗

bioRxiv2020

Genetic variants for head size share genes and pathways with cancer

The size of the human head is determined by growth in the first years of life, while the rest of the body typically grows until early adulthood1. Such complex developmental processes are regulated by various genes and growth pathways2. Rare genetic syndromes have revealed genes that affect head size3, but the genetic drivers of variation in head size within the general population remain largely unknown. To elucidate biological pathways underlying the growth of the human head, we performed the largest genome-wide association study on human head size to date (N = 79,107). We identified 67 genetic loci, 50 of which are novel, and found that these loci are preferentially associated with head size and mostly independent from height. In subsequent neuroimaging analyses, the majority of genetic variants demonstrated widespread effects on the brain, whereas the effects of 17 variants could be localized to one or two specific brain regions. Through hypothesis-free approaches, we find a strong overlap of head size variants with both cancer pathways and cancer genes. Gene set analyses showed enrichment for different types of cancer and the p53, Wnt and ErbB signalling pathway. Genes overlapping or close to lead variants - such as TP53, PTEN and APC - were enriched for genes involved in macrocephaly syndromes (up to 37-fold) and high-fidelity cancer genes (up to 9-fold), whereas this enrichment was not seen for human height variants. This indicates that genes regulating early brain and cranial growth are associated with a propensity to neoplasia later in life, irrespective of height. Our results warrant further investigations of the link between head size and cancer, as well as its clinical implications in the general population.

genomics↗

bioRxiv2020

In-vitro study of the activity of some medicinal plant leaf extracts on urinary tract infection causing bacterial pathogens isolated from indigenous people of Bolangir district, Odisha, India

Thousands of people over the world are suffering from Urinary tract infection (UTI) each day. Side effects associated with the most preferred allopathic treatment for UTI and antibiotic resistance shown by the pathogens has evolved as major challenge. Owing to this, the present study was carried out to identify the bacterial UTI pathogens among indigenous people of Bolangir district, Odisha, India vis-a-vis explore the alternative source of natural therapeutics. Bacterial pathogens causing the UTIs were identified using the colony morphology, Grams staining and biochemical characterization techniques. Microbial inhibitory test of antibiotics and leaf extracts were performed using the disc diffusion and well diffusion techniques respectively. MIC and MLC were determined by broth dilution method. Binary probit model was used to determine the prevalence of UTI across people of different age group and gender. Four bacterial strains namely Escherichia coli, Enterococcus faecalis, Staphylococcus aureus, and Klebsiella pneumoniae were identified as the causative agents of UTI among the people. The E. coli was identified as most infectious while S. aureus as the least infectious pathogen. Females in the age group of 16-30 years and male within 61-75 years were more susceptible to UTI. Among the tested leaf extracts, Tamarindus indica and Clitoria ternatea were more effective to treat UTI as compared to the tested antibiotics Ceftriaxone and Piperacillin. The leaf extracts of T. indica and C. ternatea may effectively be utilized for herbal drug development for treatment of UTI.

microbiology↗

bioRxiv2020

MicroRNA-19b regulates proliferation and differentiation along the medial-lateral axis of the developing avian pallium

Unlike the six-layered organization of neurons in the mammalian neocortex, the avian pallium features spatially-segregated neuronal clusters with partially conserved gene expression. While efforts to uncover similarities between the avian pallium and mammalian neocortex have persisted, the mechanisms of pallial development in birds have not been comprehensively explored. Here, we have established the role of a highly conserved microRNA, miR-19b, in controlling proliferation in the embryonic avian forebrain, by regulating the expression of E2f8, a cell-cycle inhibitor and NeuroD1, a neuronal differentiation factor. Further, investigation revealed that there exists a proliferation-dependent specification of pallial neurons in birds, similar to that in mammals. In summary, these findings suggest a profound role of miR-19b in shaping the avian pallium and indicate a closer resemblance of developmental mechanisms between the avian pallium and the mammalian neocortex.

developmental biology↗

bioRxiv2020

Dispersal evolution diminishes the negative density dependence in dispersal

In many organisms, dispersal varies with the local population density. Such patterns of density-dependent dispersal (DDD) are expected to shape the dynamics, spatial spread and invasiveness of populations. Despite their ecological importance, empirical evidence for the evolution of DDD patterns remains extremely scarce. This is especially relevant because rapid evolution of dispersal traits has now been empirically confirmed in several taxa. Changes in DDD of dispersing populations could help clarify not only the role of DDD in dispersal evolution, but also the possible pattern of subsequent range expansion. Here, we investigate the relationship between dispersal evolution and DDD using a long-term experimental evolution study on Drosophila melanogaster. We compared the DDD patterns of four dispersal-selected populations and their non-selected controls. The control populations showed negative DDD, which was stronger in females than in males. In contrast, the dispersal-selected populations showed density-independent dispersal, where neither males nor females exhibited DDD. We compare our results with previous evolutionary predictions that focused largely on positive DDD, and highlight how the direction of evolutionary change depends on the initial DDD pattern of a population. Finally, we discuss the implications of DDD evolution for spatial ecology and evolution.

evolutionary biology↗

bioRxiv2020

Mutation landscape of SARS-CoV-2 reveals three mutually exclusive clusters of leading and trailing single nucleotide substitutions

The COVID-19 pandemic has spread across the globe at an alarming rate. However, unlike any of the previous global outbreaks the availability of a large number of SARS-CoV-2 sequences provides us with a unique opportunity to understand viral evolution in real time. We analysed 1448 full-length (>29000 nt) sequences available and identified 40 single-nucleotide substitutions occurring in >1% of the genomes. Majority of the substitutions were C to T or G to A. We identify C/Gs with an upstream TTT trinucleotide motif as hotspots for mutations in the SARS-CoV-2 genome. Interestingly, three of the 40 substitutions occur within highly conserved secondary structures in the 5 and 3 regions of the genomic RNA that are critical for the virus life cycle. Furthermore, clustering analysis revealed unique geographical distribution of SARS-CoV-2 variants defined by their mutation profile. Of note, we observed several co-occurring mutations that almost never occur individually. We define five mutually exclusive lineages (A1, B1, C1, D1 and E1) of SARS-CoV-2 which account for about three quarters of the genomes analysed. We identify lineage-defining leading mutations in the SARS-CoV-2 genome which precede the occurrence of sub-lineage defining trailing mutations. The identification of mutually exclusive lineage-defining mutations with geographically restricted patterns of distribution has potential implications for diagnosis, pathogenesis and vaccine design. Our work provides novel insights on the temporal evolution of SARS-CoV-2. ImportanceThe SARS-CoV-2 / COVID-19 pandemic has spread far and wide with high infectivity. However, the severeness of the infection as well as the mortality rates differ greatly across different geographic areas. Here we report high frequency mutations in the SARS-CoV-2 genomes which show the presence of linage-defining, leading and trailing mutations. Moreover, we propose for the first time, five mutually exclusive clusters of SARS-CoV-2 which account for 75% of the genomes analysed. This will have implications in diagnosis, pathogenesis and vaccine design

genomics↗

bioRxiv2020

scRNA-seq reveals ACE2 and TMPRSS2 expression in TROP2+ Liver Progenitor Cells: Implications in COVID-19 associated Liver Dysfunction

The recent pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 was first reported in China (December 2019) and now prevalent in [~]170 countries across the globe. Entry of SARS-CoV-2 into mammalian cells require the binding of viral Spike (S) proteins to the ACE2 (angiotensin converting enzyme 2) receptor. Once entered the S protein is primed by a specialised serine protease, TMPRSS2 (Transmembrane Serine Protease 2) in the host cell. Importantly, beside respiratory symptoms, consistent with other common respiratory virus infection when patients become viraemic, a significant number of COVID-19 patients also develop liver comorbidities. We explored if specific target cell-type in the mammalian liver, could be implicated in disease pathophysiology other than the general deleterious response to cytokine storms. Here we employed single-cell RNA-seq (scRNA-seq) to survey the human liver and identified potentially implicated liver cell-type for viral ingress. We report the co-expression of ACE2 and TMPRSS2 in a TROP2+ liver progenitor population. Importantly, we fail to detect the expression of ACE2 in hepatocyte or any other liver (immune and stromal) cell types. These results indicated that in COVID-19 associated liver dysfunction and cell death, viral infection of TROP2+ progenitors in liver may significantly impaired liver regeneration and could lead to pathology. Highlights- EPCAM+ Liver progenitors co-express ACE2 and TMPRSS2 - ACE2 and TMPRSS2 expression is highest in TROP2high progenitors - ACE2 and TMPRSS2 cells express cholangiocyte biased fate markers - ACE2 and TMPRSS2 positive cells are absent in human fetal liver

genomics↗

bioRxiv2020

AIRBP: Accurate identification of RNA-binding proteins using machine learning techniques

MotivationIdentification of RNA-binding proteins (RBPs) that bind to ribonucleic acid molecules, is an important problem in Computational Biology and Bioinformatics. It becomes indispensable to identify RBPs as they play crucial roles in post-transcriptional control of RNAs and RNA metabolism as well as have diverse roles in various biological processes such as splicing, mRNA stabilization, mRNA localization, and translation, RNA synthesis, folding-unfolding, modification, processing, and degradation. The existing experimental techniques for identifying RBPs are time-consuming and expensive. Therefore, identifying RBPs directly from the sequence using computational methods can be useful to efficiently annotate RBPs and assist the experimental design. In this work, we present a method, called AIRBP, which is designed using an advanced machine learning technique, called stacking, to effectively predict RBPs by utilizing features extracted from evolutionary information, physiochemical properties, and disordered properties. Moreover, our method, AIRBP is trained on the useful feature-subset identified by the evolutionary algorithm (EA). ResultsThe results show that AIRBP attains Accuracy (ACC), F1-score, and MCC of 95.38%, 0.917, and 0.885, respectively, based on the benchmark dataset, using 10-fold cross-validation (CV). Further evaluation of AIRBP on independent test set reveals that it achieves ACC, F1-score, and MCC of 93.04%, 0.943, and 0.855, for Human test set; 91.60%, 0.942 and 0.789 for S. cerevisiae test set; and 91.67%, 0.953 and 0.594 for A. thaliana test set, respectively. These results indicate that AIRBP outperforms the current state-of-the-art method. Therefore, the proposed top-performing AIRBP can be useful for accurate identification and annotation of RBPs directly from the sequence and help gain valuable insight to treat critical diseases. AvailabilityCode-data is available here: http://cs.uno.edu/~tamjid/Software/AIRBP/code_data.zip

bioinformatics↗