Small Set Of Genes Research Articles

Transcriptome analysis of putative detoxification genes in the Asian citrus psyllid, Diaphorina citri.

The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Psyllidae), is a notorious pest that transmits the causal agent of huanglongbing (also called citrus greening disease). Resistance to insecticide in this destructive pest poses a serious threat to the citrus industry. To date, no systemic studies on genes coding for detoxification enzymes has been carried out on D. citri. Multiple transcriptomes were generated through deep sequencing of RNA libraries. Candidate genes potentially involved in detoxification including cytochrome P450 monooxygenases (CYPs), glutathione S-transferases (GSTs), and esterases (ESTs) were systematically identified by searching the transcriptomes and a draft genome assembly. A total of 49, 14 and 20 genes were found encoding CYPs, GSTs, and ESTs, respectively, in D. citri. The total numbers of candidate detoxification genes were much smaller than the counterparts reported in other insect species, which may reflect the strict oligophagy of this insect species. Developmental stage- and tissue-specific expression patterns of the identified genes as well as their responses to insecticide treatments identified a small set of genes that could participate in detoxifying plant secondary metabolites and insecticides. Our studies represent the most comprehensive investigation to date on identification, characterization and expression profiling of detoxification genes in D. citri. The information revealed in this study shall be useful in designing strategies to manage this important insect pest. © 2020 Society of Chemical Industry.

Effect of phyB and phyC loss-of-function mutations on the wheat transcriptome under short and long day photoperiods

BackgroundPhotoperiod signals provide important cues by which plants regulate their growth and development in response to predictable seasonal changes. Phytochromes, a family of red and far-red light receptors, play critical roles in regulating flowering time in response to changing photoperiods. A previous study showed that loss-of-function mutations in either PHYB or PHYC result in large delays in heading time and in the differential regulation of a large number of genes in wheat plants grown in an inductive long day (LD) photoperiod.ResultsWe found that under non-inductive short-day (SD) photoperiods, phyB-null and phyC-null mutants were taller, had a reduced number of tillers, longer and wider leaves, and headed later than wild-type (WT) plants. The delay in heading between WT and phy mutants was greater in LD than in SD, confirming the importance of PHYB and PHYC in accelerating heading date in LDs. Both mutants flowered earlier in SD than LD, the inverse response to that of WT plants. In both SD and LD photoperiods, PHYB regulated more genes than PHYC. We identified subsets of differentially expressed and alternatively spliced genes that were specifically regulated by PHYB and PHYC in either SD or LD photoperiods, and a smaller set of genes that were regulated in both photoperiods. We found that photoperiod had a contrasting effect on transcript levels of the flowering promoting genes VRN-A1 and PPD-B1 in phyB and phyC mutants compared to the WT.ConclusionsOur study confirms the major role of both PHYB and PHYC in flowering promotion in LD conditions. Transcriptome characterization revealed an unexpected reversion of the wheat LD plants into SD plants in the phyB-null and phyC-null mutants and identified flowering genes showing significant interactions between phytochromes and photoperiod that may be involved in this phenomenon. Our RNA-seq data provides insight into light signaling pathways in inductive and non-inductive photoperiods and a set of candidate genes to dissect the underlying developmental regulatory networks in wheat.

Predicting brain metastasis in early stage non-small cell lung cancer patients by gene expression profiling.

BackgroundNon-small cell lung cancer (NSCLC) is the most common cause of cancer-death due to early metastatic spread, in many cases primarily to the brain. Organ-specific pattern of spread of disease might be driven by the activity of a specific signaling pathway within the primary tumors. We aimed to identify an expression signature of genes and the relevant signaling associated with the development of brain metastasis (BM) after surgical resection of NSCLC.MethodsRapidly frozen NSCLC surgical specimens were procured from tumor banks. RNA was extracted and analyzed by RNA-sequencing (Illumina HiSeq 2500). Clinical parameters and gene expression were examined for differentiating between patients with BM, patients with metastases to sites other than brain, and patients who did not develop metastatic disease at a clinically significant follow up. Principal component analysis and pathway enrichments studies were done.ResultsA total of 91 patients were included in this study, 32 of which developed BM. Stage of disease at diagnosis (P=0.004) and level of differentiation (P=0.007) were significantly different between BM and control group. We identified a set of 22 genes which correlated specifically with BM, and not with metastasis to other sites. This set achieved 93.4% accuracy (95% CI: 86.2–97.5%), 96.6% specificity and 87.5% sensitivity of correctly identifying BM patients in a leave-one-out internal validation analysis. The oxidative phosphorylation pathway was strongly correlated with BM risk.ConclusionsExpression level of a small set of genes from primary tumors was found to predict BM development, distinctly from metastasis to other organs. These genes and the correlated oxidative phosphorylation pathway require further validation as potentially clinically useful predictors of BM and possibly as novel therapeutic targets for BM prevention.

WERFE: A Gene Selection Algorithm Based on Recursive Feature Elimination and Ensemble Strategy.

Gene selection algorithm in micro-array data classification problem finds a small set of genes which are most informative and distinctive. A well-performed gene selection algorithm should pick a set of genes that achieve high performance and the size of this gene set should be as small as possible. Many of the existing gene selection algorithms suffer from either low performance or large size. In this study, we propose a wrapper gene selection approach, named WERFE, within a recursive feature elimination (RFE) framework to make the classification more efficient. This WERFE employs an ensemble strategy, takes advantages of a variety of gene selection methods and assembles the top selected genes in each approach as the final gene subset. By integrating multiple gene selection algorithms, the optimal gene subset is determined through prioritizing the more important genes selected by each gene selection method and a more discriminative and compact gene subset can be selected. Experimental results show that the proposed method can achieve state-of-the-art performance.

Validation of an exome and transcriptome based diagnostic platform enabling clinical cancer therapy selection and emerging composite biomarkers for immunotherapy.

e15583 Background: While immunotherapy has become a pillar of cancer treatment, diagnostic biomarkers that consistently predict patient response to these therapies have remained elusive. There is an increasing need for the development of integrative, composite biomarkers that can model the complex biology driving response and/or resistance to immunotherapy more effectively than existing single-analyte approaches. However, the majority of current cancer diagnostic panels, with their focus on a small set of genes, provide limited ability to support these emerging advanced biomarkers. Methods: To address these limitations, we developed and validated NeXT Dx, a comprehensive enhanced exome and transcriptome based diagnostic platform designed to simultaneously characterize tumor and immune genomics from a single limited FFPE sample. To achieve higher accuracy and sensitivity for an exome scale diagnostic platform, we developed an augmented exome assay that improves uniformity of coverage across all ~20,000 genes, including boosted coverage of 248 clinically-relevant cancer genes. We validated this assay using genomic DNA and RNA extracted from tumor-derived cell-lines, constructs, clinical FFPE samples, and proficiency testing samples. The assay utilizes > = 25ng of co-extracted DNA and RNA which were sequenced using Illumina NovaSeq instruments at our CAP-accredited, CLIA-certified laboratory. Additional assay enhancements for HLA, immune repertoire, and oncoviruses were designed to further optimize the platform for immunotherapy biomarker discovery applications. Results: Validation of NeXT Dx demonstrated a performance of 99.5% sensitivity and 99.8% positive predictive value (PPV) for SNVs with > = 5% AF; 98.7% sensitivity and 97.4% PPV for indels with > = 10% AF; 97.2% sensitivity and 94.6% PPV for CNAs in samples with > = 30% tumor content; 94.9% sensitivity and 94.9% PPV for fusions; and a 2.1% error rate for MSI classification. TMB was calculated using gold-standard whole exome data from SNVs and indels. Typical median coverage depth was > 1,000X for 248 clinically-relevant genes, ~300X for the remaining (whole exome) footprint. Conclusions: With NeXT Dx, we demonstrate a exome/transcriptome scale diagnostic platform that can detect current clinical biomarkers with high sensitivity as well as support emerging, advanced biomarkers that integrate across both tumor and immune features.

MON-031 A Gene Expression Profile of the Adolescent Breast and the Impact of Obesity

Environmental exposures that occur early in life affect breast development and breast cancer (BC) risk in adulthood. Puberty is one such developmental ‘window of susceptibility’ when estrogen (E) stimulates breast adipocytes and stromal and epithelial cells to proliferate at an exponential rate, making them vulnerable to carcinogens. Excess adiposity during adulthood may increase BC risk through obesity-associated inflammation and/or aromatase activity, which increases local E levels. While obesity during puberty might be expected to also increase future BC risk, epidemiological studies suggest that pediatric obesity may actually be protective. The current studies investigated the gene expression profile of the normal adolescent breast and how early life factors such as obesity may influence these profiles.We performed RNA-seq in 62 histologically-normal breast tissue samples from adolescent girls and young women (mean age 17.8 yrs) who underwent breast reduction surgery. Twenty-nine patients were normal weight (NW; mean BMI 23.2 kg/m2) and 33 were overweight/obese (OB; BMI 31.7). Comparison of our adolescent dataset with published mammary RNAseq datasets from pubertal mice, rats, macaques, and adult women (mean age 38 yrs) revealed relatively poor (~ 30%) overlap with other species, but 88% overlap with adults for the 500 most highly expressed genes in each dataset. The small gene set (n=43) common to all groups was enriched for extracellular matrix components.We used DESeq2 to identify differentially-expressed (DE) genes in NW vs OB samples. To avoid confounding due to differences in the cellular composition of NW and OB samples, we first used CIBERSORT to computationally estimate the adipocyte fraction of each sample and included this estimate as a covariate. We identified 74 up-regulated and 73 down-regulated genes in NW vs. OB (padj < 0.05). We used Ingenuity Pathway Analysis (IPA) to determine whether the DE genes might reflect activation or inhibition of upstream transcriptional regulators in OB samples. IPA identified the cytokines CSF1 and CSF2 and the chemokine receptor CCR2 as the most highly activated upstream regulators, suggesting a signature of increased inflammation in OB samples. While classical E receptor (ER) targets (e.g., PR, AREG) were not DE’d, IPA identified ESR1, 17-α-ethinyl estradiol, genistein, and PR, as well as growth factors/receptors (EGF, IGF-1, HGF, HER3) and kinases (AKT1, ERK) involved in hormone-independent ER activation, as activated upstream regulators in OB samples.These studies represent the first investigation of the human breast transcriptome during late puberty and demonstrate that in adolescents, as in adults, OB is associated with increased inflammation which may augment E action in the breast microenvironment.

A MAGEL2-deubiquitinase complex modulates the ubiquitination of circadian rhythm protein CRY1.

MAGEL2 encodes the L2 member of the MAGE (melanoma antigen) protein family. Protein truncating mutations in MAGEL2 cause Schaaf-Yang syndrome, and MAGEL2 is one of a small set of genes deleted in Prader-Willi syndrome. Excessive daytime sleepiness, night-time or early morning waking, and narcoleptic symptoms are seen in people with Prader-Willi syndrome and Schaaf-Yang syndrome, while mice carrying a gene-targeted Magel2 deletion have disrupted circadian rhythms. These phenotypes suggest that MAGEL2 is important for the robustness of the circadian rhythm. However, a cellular role for MAGEL2 has yet to be elucidated. MAGEL2 influences the ubiquitination of substrate proteins to target them for further modification or to alter their stability through proteasomal degradation pathways. Here, we characterized relationships among MAGEL2 and proteins that regulate circadian rhythm. The effect of MAGEL2 on the key circadian rhythm protein cryptochrome 1 (CRY1) was assessed using in vivo proximity labelling (BioID), immunofluorescence microscopy and ubiquitination assays. We demonstrate that MAGEL2 modulates the ubiquitination of CRY1. Further studies will clarify the cellular role MAGEL2 normally plays in circadian rhythm, in part through ubiquitination and regulation of stability of the CRY1 protein.

Prediction of cell position using single-cell transcriptomic data: an iterative procedure.

Single-cell sequencing reveals cellular heterogeneity but not cell localization. However, by combining single-cell transcriptomic data with a reference atlas of a small set of genes, it would be possible to predict the position of individual cells and reconstruct the spatial expression profile of thousands of genes reported in the single-cell study. With the purpose of developing new algorithms, the Dialogue for Reverse Engineering Assessments and Methods (DREAM) consortium organized a crowd-sourced competition known as DREAM Single Cell Transcriptomics Challenge (SCTC). Within this context, we describe here our proposed procedures for adequate reference genes selection, and an iterative procedure to predict spatial expression profile of other genes.

Transcriptome profiling of Variovorax paradoxus EPS under different growth conditions reveals regulatory and structural novelty in biofilm formation.

We used transcriptome analysis by paired-end strand-specific RNA-seq to evaluate the specific changes in gene expression associated with the transition to static biofilm growth in the rhizosphere plant growth-promoting bacterium Variovorax paradoxus EPS. Triplicate biological samples of exponential growth, stationary phase and static biofilm samples were examined. DESeq2 and Rockhopper were used to identify robust and widespread shifts in gene expression specific to each growth phase. We identified 1711 protein-coding genes (28%) using DESeq2 that had altered expression greater than twofold specifically in biofilms compared to exponential growth. Fewer genes were specifically differentially expressed in stationary-phase culture (757, 12%). A small set of genes (103/6020) were differentially expressed in opposing fashions in biofilm and stationary phase, indicating potentially substantial shifts in phenotype. Gene-ontology analysis showed that the only class of genes specifically upregulated in biofilms was associated with nutrient transport, highlighting the importance of nutrient uptake in the biofilm. The biofilm-specific genes did not overlap substantially with the loci identified by mutagenesis studies, although some were present in both sets. The most highly upregulated biofilm-specific gene is predicted to be a part of the RNA degradosome, which indicates that RNA stability is used to regulate the biofilm phenotype. Two small putative proteins, Varpa_0407 and Varpa_3832, are highly expressed specifically in biofilms and are predicted to be secreted DNA-binding proteins, which may stabilize extracellular DNA as a component of the biofilm matrix. An flp/tad type-IV pilus locus (Varpa_5148–60) is strongly downregulated specifically in biofilms, in contrast with results from other systems for these pili. Mutagenesis confirms that this locus is important in surface motility rather than biofilm formation. These experimental results suggest that V. paradoxus EPS biofilms have substantial regulatory and structural novelty.

Co-localization between Sequence Constraint and Epigenomic Information Improves Interpretation of Whole-Genome Sequencing Data

The identification of functional regions in the noncoding human genome is difficult but critical in order to gain understanding of the role noncoding variation plays in gene regulation in human health and disease. We describe here a co-localization approach that aims to identify constrained sequences that co-localize with tissue- or cell-type-specific regulatory regions, and we show that the resulting score is particularly well suited for the identification of rare regulatory variants. For 127 tissues and cell types in the ENCODE/Roadmap Epigenomics Project, we provide catalogs of putative tissue- or cell-type-specific regulatory regions under sequence constraint. We use the newly developed co-localization score for brain tissues to score de novo mutations in whole genomes from 1,902 individuals affected with autism spectrum disorder (ASD) and their unaffected siblings in the Simons Simplex Collection. We show that noncoding de novo mutations near genes co-expressed in midfetal brain with high confidence ASD risk genes, and near FMRP gene targets are more likely to be in co-localized regions if they occur in ASD probands versus in their unaffected siblings. We also observed a similar enrichment for mutations near lincRNAs, previously shown to co-express with ASD risk genes. Additionally, we provide strong evidence that prioritized denovo mutations in autism probands point to a small set of well-known ASD genes, the disruption of which produces relevant mouse phenotypes such as abnormal social investigation and abnormal discrimination/associative learning, unlike the de novo mutations in unaffected siblings. The genome-wide co-localization results are available online.

A method to generate multilocus barcodes of pinned insect specimens using MiSeq.

For molecular insect identification, amplicon sequencing methods are recommended because they offer a cost-effective approach for targeting small sets of informative genes from multiple samples. In this context, high-throughput multilocus amplicon sequencing has been achieved using the MiSeq Illumina sequencing platform. However, this approach generates short gene fragments of <500bp, which then have to be overlapped using bioinformatics to achieve longer sequence lengths. This increases the risk of generating chimeric sequences or leads to the formation of incomplete loci. Here, we propose a modified nested amplicon sequencing method for targeting multiple loci from pinned insect specimens using the MiSeq Illumina platform. The modification exists in using a three-step nested PCR approach targeting near full-length loci in the initial PCR and subsequently amplifying short fragments of between 300 and 350bp for high-throughput sequencing using Illumina chemistry. Using this method, we generated 407 sequences of three loci from 86% of all the specimens sequenced. Out of 103 pinned bee specimens of replicated species, 71% passed the 95% sequence similarity threshold between species replicates. This method worked best for pinned specimens aged between 0 and 5years, with a limit of 10years for pinned and 14years for ethanol-preserved specimens. Hence, our method overcomes some of the challenges of amplicon sequencing using short read next generation sequencing and improves the possibility of creating high-quality multilocus barcodes from insect collections.

A Pivotal Genetic Program Controlled by Thyroid Hormone during the Maturation of GABAergic Neurons.

SummaryMammalian brain development critically depends on proper thyroid hormone signaling, via the TRα1 nuclear receptor. The downstream mechanisms by which TRα1 impacts brain development are currently unknown. In order to investigate these mechanisms, we used mouse genetics to induce the expression of a dominant-negative mutation of TRα1 specifically in GABAergic neurons, the main inhibitory neurons in the brain. This triggered post-natal epileptic seizures and a profound impairment of GABAergic neuron maturation in several brain regions. Analysis of the transcriptome and TRα1 cistrome in the striatum allowed us to identify a small set of genes, the transcription of which is upregulated by TRα1 in GABAergic neurons and which probably plays an important role during post-natal maturation of the brain. Thus, our results point to GABAergic neurons as direct targets of thyroid hormone during brain development and suggest that many defects seen in hypothyroid brains may be secondary to GABAergic neuron malfunction.

End of the road for the « homosexuality gene »

Evidence for a "homosexuality gene" was claimed in the early 1990's on the basis of linkage studies that, by current criteria, were woefully underpowered. Indeed, follow up studies gave contradictory results. Genome-wide association studies, and very large databases with detailed genetic and phenotypic data, have made possible a re-examination of this issue. While modest heritability (ca. 0.3) for homosexuality is confirmed, no major locus is found and the genetic influence appears extremely polygenic. Thus, there is no single gene, or even small set of genes, that have a strong influence on homosexuality.

Constitutive and Plastic Gene Expression Variation Associated with Desiccation Resistance Differences in the Drosophila americana Species Group.

Stress response mechanisms are ubiquitous and important for adaptation to heterogenous environments and could be based on constitutive or plastic responses to environmental stressors. Here we quantify constitutive and plastic gene expression differences under ambient and desiccation stress treatments, in males and females of three species of Drosophila known to differ in desiccation resistance. Drosophila novamexicana survives desiccation trials significantly longer than the two subspecies of Drosophila americana, consistent with its natural species range in the desert southwest USA. We found that desiccation stress reduces global expression differences between species—likely because many general stress response mechanisms are shared among species—but that all species showed plastic expression changes at hundreds of loci during desiccation. Nonetheless, D. novamexicana had the fewest genes with significant plastic expression changes, despite having the highest desiccation resistance. Of the genes that were significantly differentially expressed between species—either within each treatment (>200 loci), constitutively regardless of treatment (36 loci), or with different species-specific plasticity (26 loci)—GO analysis did not find significant enrichment of any major gene pathways or broader functions associated with desiccation stress. Taken together, these data indicate that if gene expression changes contribute to differential desiccation resistance between species, these differences are likely shaped by a relatively small set of influential genes rather than broad genome-wide differentiation in stress response mechanisms. Finally, among the set of genes with the greatest between-species plasticity, we identified an interesting set of immune-response genes with consistent but opposing reaction norms between sexes, whose potential functional role in sex-specific mechanisms of desiccation resistance remains to be determined.

Comparative Pangenomics of the Mammalian Gut Commensal Bifidobacterium longum.

Bifidobacterium longum colonizes mammalian gastrointestinal tracts where it could metabolize host-indigestible oligosaccharides. Although B. longum strains are currently segregated into three subspecies that reflect common metabolic capacities and genetic similarity, heterogeneity within subspecies suggests that these taxonomic boundaries may not be completely resolved. To address this, the B. longum pangenome was analyzed from representative strains isolated from a diverse set of sources. As a result, the B. longum pangenome is open and contains almost 17,000 genes, with over 85% of genes found in ≤28 of 191 strains. B. longum genomes share a small core gene set of only ~500 genes, or ~3% of the total pangenome. Although the individual B. longum subspecies pangenomes share similar relative abundances of clusters of orthologous groups, strains show inter- and intrasubspecies differences with respect to carbohydrate utilization gene content and growth phenotypes.

A Snapshot of the Trehalose Pathway During Seed Imbibition in Medicago truncatula Reveals Temporal- and Stress-Dependent Shifts in Gene Expression Patterns Associated With Metabolite Changes.

Trehalose, a non-reducing disaccharide with multiple functions, among which source of energy and carbon, stress protectant, and signaling molecule, has been mainly studied in relation to plant development and response to stress. The trehalose pathway is conserved among different organisms and is composed of three enzymes: trehalose-6-phosphate synthase (TPS), which converts uridine diphosphate (UDP)-glucose and glucose-6-phosphate to trehalose-6-phosphate (T6P), trehalose-6-phosphatase (TPP), which dephosphorylates T6P to produce trehalose, and trehalase (TRE), responsible for trehalose catabolism. In plants, the trehalose pathway has been mostly studied in resurrection plants and the model plant Arabidopsis thaliana, where 11 AtTPS, 10 AtTPP, and 1 AtTRE genes are present. Here, we aim to investigate the involvement of the trehalose pathway in the early stages of seed germination (specifically, seed imbibition) using the model legume Medicago truncatula as a working system. Since not all the genes belonging to the trehalose pathway had been identified in M. truncatula, we first conducted an in silico analysis using the orthologous gene sequences from A. thaliana. Nine MtTPSs, eight MtTPPs, and a single MtTRE gene were hereby identified. Subsequently, the expression profiles of all the genes (together with the sucrose master-regulator SnRK1) were investigated during seed imbibition with water or stress agents (polyethylene glycol and sodium chloride). The reported data show a temporal distribution and preferential expression of specific TPS and TPP isoforms during seed imbibition with water. Moreover, it was possible to distinguish a small set of genes (e.g., MtTPS1, MtTPS7, MtTPS10, MtTPPA, MtTPPI, MtTRE) having a potential impact as precocious hallmarks of the seed response to stress. When the trehalose levels were measured by high-performance liquid chromatography, a significant decrease was observed during seed imbibition, suggesting that trehalose may act as an energy source rather than osmoprotectant. This is the first report investigating the expression profiles of genes belonging to the trehalose pathway during seed imbibition, thus ascertaining their involvement in the pre-germinative metabolism and their potential as tools to improve seed germination efficiency.

A cell-based probabilistic approach unveils the concerted action of miRNAs.

Mature microRNAs (miRNAs) regulate most human genes through direct base-pairing with mRNAs. We investigate the underlying principles of miRNA regulation in living cells. To this end, we overexpressed miRNAs in different cell types and measured the mRNA decay rate under a paradigm of a transcriptional arrest. Based on an exhaustive matrix of mRNA-miRNA binding probabilities, and parameters extracted from our experiments, we developed a computational framework that captures the cooperative action of miRNAs in living cells. The framework, called COMICS, simulates the stochastic binding events between miRNAs and mRNAs in cells. The input of COMICS is cell-specific profiles of mRNAs and miRNAs, and the outcome is the retention level of each mRNA at the end of 100,000 iterations. The results of COMICS from thousands of miRNA manipulations reveal gene sets that exhibit coordinated behavior with respect to all miRNAs (total of 248 families). We identified a small set of genes that are highly responsive to changes in the expression of almost any of the miRNAs. In contrast, about 20% of the tested genes remain insensitive to a broad range of miRNA manipulations. The set of insensitive genes is strongly enriched with genes that belong to the translation machinery. These trends are shared by different cell types. We conclude that the stochastic nature of miRNAs reveals unexpected robustness of gene expression in living cells. By applying a systematic probabilistic approach some key design principles of cell states are revealed, emphasizing in particular, the immunity of the translational machinery vis-a-vis miRNA manipulations across cell types. We propose COMICS as a valuable platform for assessing the outcome of miRNA regulation of cells in health and disease.

A TRIZ-inspired bat algorithm for gene selection in cancer classification

Gene expression data are expected to make a great contribution in the producing of efficient cancer diagnosis and prognosis. Gene expression data are coded by large measured genes, and only of a few number of them carry precious information for different classes of samples. Recently, several researchers proposed gene selection methods based on metaheuristic algorithms for analysing and interpreting gene expression data. However, due to large number of selected genes with limited number of patient's samples and complex interaction between genes, many gene selection methods experienced challenges in order to approach the most relevant and reliable genes. Hence, in this paper, a hybrid filter/wrapper, called rMRMR-MBA is proposed for gene selection problem. In this method, robust Minimum Redundancy Maximum Relevancy (rMRMR) as filter to select the most promising genes and an modified bat algorithm (MBA) as search engine in wrapper approach is proposed to identify a small set of informative genes. The performance of the proposed method has been evaluated using ten gene expression datasets. For performance evaluation, MBA is evaluated by studying the convergence behaviour of MBA with and without TRIZ optimisation operators. For comparative evaluation, the results of the proposed rMRMR-MBA were compared against ten state-of-arts methods using the same datasets. The comparative study demonstrates that the proposed method produced better results in terms of classification accuracy and number of selected genes in two out of ten datasets and competitive results on the remaining datasets. In a nutshell, the proposed method is able to produce very promising results with high classification accuracy which can be considered a promising contribution for gene selection domain.

First confirmatory study on PTPRQ as an autosomal dominant non-syndromic hearing loss gene

BackgroundBiallelic PTPRQ pathogenic variants have been previously reported as causative for autosomal recessive non-syndromic hearing loss. In 2018 the first heterozygous PTPRQ variant has been implicated in the development of autosomal dominant non-syndromic hearing loss (ADNSHL) in a German family. The study presented the only, so far known, PTPRQ pathogenic variant (c.6881G>A) in ADNSHL. It is located in the last PTPRQ coding exon and introduces a premature stop codon (p.Trp2294*).MethodsA five-generation Polish family with ADNSHL was recruited for the study (n = 14). Thorough audiological, neurotological and imaging studies were carried out to precisely define the phenotype. Genomic DNA was isolated from peripheral blood samples or buccal swabs of available family members. Clinical exome sequencing was conducted for the proband. Family segregation analysis of the identified variants was performed using Sanger sequencing. Single nucleotide polymorphism array on DNA samples from the Polish and the original German family was used for genome-wide linkage analysis.ResultsCombining clinical exome sequencing and family segregation analysis, we have identified the same (NM_001145026.2:c.6881G>A, NP_001138498.1:p.Trp2294*) PTPRQ alteration in the Polish ADNSHL family. Using genome-wide linkage analysis, we found that the studied family and the original German family derive from a common ancestor. Deep phenotyping of the affected individuals showed that in contrast to the recessive form, the PTPRQ-related ADNSHL is not associated with vestibular dysfunction. In both families ADNSHL was progressive, affected mainly high frequencies and had a variable age of onset.ConclusionOur data provide the first confirmation of PTPRQ involvement in ADNSHL. The finding strongly reinforces the inclusion of PTPRQ to the small set of genes leading to both autosomal recessive and dominant hearing loss.

Differential Expression of Candidate Salivary Effector Genes in Pea Aphid Biotypes With Distinct Host Plant Specificity.

Effector proteins play crucial roles in determining the outcome of various plant-parasite interactions. Aphids inject salivary effector proteins into plants to facilitate phloem feeding, but some proteins might trigger defense responses in certain plants. The pea aphid, Acyrthosiphon pisum, forms multiple biotypes, and each biotype is specialized to feed on a small number of closely related legume species. Interestingly, all the previously identified biotypes can feed on Vicia faba; hence, it serves as a universal host plant of A. pisum. We hypothesized that the salivary effector proteins have a key role in determining the compatibility between specific host species and A. pisum biotypes and that each biotype produces saliva containing a specific mixture of effector proteins due to differential expression of encoding genes. As the first step to address these hypotheses, we conducted two sets of RNA-seq experiments. RNA-seq analysis of dissected salivary glands (SGs) from reference alfalfa- and pea-specialized A. pisum lines revealed common and line-specific repertoires of candidate salivary effector genes. Based on the results, we created an extended catalogue of A. pisum salivary effector candidates. Next, we used aphid head samples, which contain SGs, to examine biotype-specific expression patterns of candidate salivary genes. RNA-seq analysis of head samples of alfalfa- and pea-specialized biotypes, each represented by three genetically distinct aphid lines reared on either a universal or specific host plant, showed that a majority of the candidate salivary effector genes was expressed in both biotypes at a similar level. Nonetheless, we identified small sets of genes that were differentially regulated in a biotype-specific manner. Little host plant effect (universal vs. specific) was observed on the expression of candidate salivary genes. Analysis of previously obtained genome re-sequenced data of the two biotypes revealed the copy number variations that might explain the differential expression of some candidate salivary genes. In addition, at least four candidate effector genes that were present in the alfalfa biotype but might not be encoded in the pea biotype were identified. This work sets the stage for future functional characterization of candidate genes potentially involved in the determination of plant specificity of pea aphid biotypes.