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opencc-zeroNov 2021View details →

Gene expression responses to thermal shifts in the endangered lichen Lobaria pulmonaria

Anthropogenic climate change has led to unprecedented shifts in temperature across many ecosystems. In a context of rapid environmental changes, acclimation is an important process as it may influence the capacity of organisms to survive under novel thermal conditions. Mechanisms of acclimation could involve upregulation of stress response genes involved in protein folding, DNA damage repair and the regulation of signal transduction genes, along with a simultaneous downregulation of genes involved in growth or cell cycle, in order to maintain cellular functions and equilibria. We transplanted Lobaria pulmonaria lichens originating from different forests to determine the relative effects of long-term acclimation and genetic factors on the variability in expression of mycobiont and photobiont genes. We found a strong response of mycobiont and photobiont to high temperatures, regardless of sample origin. The green-algal photobiont had an overall lower response than the mycobiont. The gene expression of both symbionts was also influenced by acclimation to transplantation sites and by genetic factors. Lobaria pulmonaria seems to have evolved powerful molecular pathways to deal with environmental fluctuations and stress and can acclimate to new habitats by transcriptomic convergence. Although L. pulmonaria has the molecular machinery to counteract short-term thermal stress, survival of lichens like L. pulmonaria depends mostly on their long-term positive carbon balance, which can be compromised by warmer temperatures and reduced precipitation, and both these outcomes have been predicted for Central Europe in connection with global climate change.

opencc-zeroDec 2021View details →

Density-by-diet interactions during larval development shape adult life-history trait expression and fitness in a polyphagous fly

Habitat quality early in life determines individual fitness, with possible long-term evolutionary effects on groups and populations. In holometabolous insects, larval ecology plays a major role in determining the expression of traits in adulthood, but how ecological conditions during larval stage interact to shape adult life-history and fitness, particularly in non-model organisms, remains subject to scrutiny. Consequently, our knowledge of the interactive effects of ecological factors on insect development is limited. Here, using the polyphagous fly Bactrocera tryoni, we conducted a fully-factorial design where we manipulated larval density and larval diet (protein-rich, standard, and sugar-rich) to gain insights into how these ecological factors interact to modulate adult fitness. As expected, a protein-rich diet resulted in faster larval development, heavier and leaner adults that were more fecund compared with standard and sugar-rich diets, irrespective of larval density. Females from the protein-rich larval diet had overall higher reproductive rate (i.e., eggs per day) than females from other diets, and reproductive rate decreased linearly with density for females from the protein-rich but non-linearly for females from the standard and sugar-rich diets over time. Surprisingly, adult lipid reserve increased with larval density for adults from the sugar-rich diet (as opposed to decreasing, as in other diets), possibly due to a stress-response to an extremely adverse condition during development (i.e., high intraspecific competition and poor nutrition). Together, our results provide insights into how ecological factors early in life interact and shape the fate of individuals through life-stages in holometabolous insects.

opencc-by-4.0Sep 2021View details →

Comparative analysis of differential gene expression indicates divergence in ontogenetic strategies of leaves in two conifer genera

Juniperus flaccida (drooping juniper) and Pinus cembroides (pinyon pine) are conifers native to North America, spanning Mexico and the Southwestern region of the United States. Although from two different lineages, both species exhibit heteroblastic growth. Morphologically, their leaves undergo a change between the juvenile and adult life stage. J. flaccida leaves appear needle-like at youth and scale-like at maturity, whereas the P. cembroides will transition from needle-like leaves to brown scale-like leaves. The objective was to perform a comparative transcriptomic analysis to quantify and examine differential expression in juvenile and adult individuals from both species. RNA from twelve samples was sequenced on HiSeq 1500 (100bp PE) and analyzed with available software. Because there are no reference genomes for these species, they were assembled de novo from the RNA-Seq reads. Following assembly, the coding regions were identified and redundant transcripts were removed. Quality filtered reads were aligned to the reference transcriptomes (one for each species), counts were generated from the alignment files, and differential expression analysis was performed with DESeq2 via Kallisto. Up and down-regulated genes (padj<0.1) across both age classes (juvenile vs adult) were observed in each species and compared.

openmit-licenseJan 2022View details →

Elucidating gene expression patterns across multiple biological contexts through a large-scale investigation of transcriptomic datasets

This contains data for described in detail in our paper, "Elucidating gene expression patterns across multiple biological contexts through a large-scale investigation of transcriptomic datasets" (Figueiredo et al., 2022) which aims at revealing common and specific biological processes and mechanisms across contexts by identifying transcriptional patterns that are unique to various cell types, tissues, and cell lines, as well as patterns which are consistent across them.

opencc-by-4.0Jan 2022View details →

CTLA-4 and PD-1 expressed in EMT6 mouse mammary carcinoma cell line acquired radio-resistance to gamma-ray irradiation.

Supplementary File of manuscript entitled CTLA-4 and PD-1 expressed in EMT6 mouse mammary carcinoma cell line acquired radio-resistance to gamma-ray irradiation.

opencc-by-4.0Feb 2022View details →

Regular expression with their instances

This dataset contains randomly generated regular expression along with a set of randomly instances for each regexp. Used to train a machine learning regexp inference model. Encoded using python 3.8 pickle  with HIGHEST_PROTOCOL.

opencc-zeroFeb 2022View details →

Negative E-cadherin expression on bone marrow myeloma cell membranes is associated with extramedullary disease

Background: The loss of E-cadherin expression and the induction of N-cadherin are known as hallmarks of the epithelial-to-mesenchymal transition, an essential initial step in the process of metastasis in solid tumors. Although several studies have reported expressions of these cadherins in patients with multiple myeloma (MM), their clinical significance is unknown as MM cells are non-epithelial. Methods: In this study, we examined the expression of E- and N-cadherins by immunohistochemistry using bone marrow (BM) biopsy specimens from 31 newly diagnosed MM patients and in subsequent biopsy specimens from six of these. Results: Negative E-cadherin expression on BM myeloma cell membranes was significantly associated with the presence of soft-tissue masses arising from bone lesions and breaking through the cortical bone, referred to as extramedullary disease (EMD). Conclusions: Given the aggressive nature of EMD, our study suggests that screening for E-cadherin using BM immunohistochemistry is one measure that could predict the development of EMD in patients with MM.

opencc-by-4.0Feb 2022View details →

Time-series transcriptome analysis identified differentially expressed genes in broiler chicken infected with mixed Eimeria species

Coccidiosis caused by the Eimeria species is a highly problematic disease in the chicken industry. Here, we used RNA sequencing to observe the time-dependent host responses of Eimeria-infected chickens to examine the genes and biological functions associated with immunity to the parasite. Transcriptome analysis was performed at three time points: 4, 7, and 21 days post-infection (dpi). Based on the changes in gene expression patterns, we defined three groups of genes that showed differential expression. This enabled us to capture evidence of endoplasmic reticulum stress at the initial stage of Eimeria infection. Furthermore, we found that innate immune responses against the parasite were activated at the first exposure; they then showed gradual normalization. Although the cytokine-cytokine receptor interaction pathway was significantly operative at 4 dpi, its downregulation led to an anti-inflammatory effect. Additionally, the construction of gene co-expression networks enabled identification of immunoregulation hub genes and critical pattern recognition receptors after Eimeria infection. Our results provide a detailed understanding of the host-pathogen interaction between chicken and Eimeria. The clusters of genes defined in this study can be utilized to improve chickens for coccidiosis control.

opencc-by-4.0Mar 2022View details →

Genetic mutations and decreased protein expression of ABCG2 urate transporters are associated with susceptibility to gout, disease severity and renal-overload hyperuricemia

We are releasing the data and code of our study of clinically defined gouty patients.

opencc-zeroMar 2022View details →

Megachile rotundata overwintering nCounter gene expression

Within the United States and Canada, the primary pollinator of alfalfa is the alfalfa leafcutting bee (ALCB), Megachile rotundata. Our previous findings showed that overwintering conditions impacted gene expression profile in ALCB prepupae that entered diapause early in the season. However, ALCB are a bivoltine species, which begs the question of whether bees entering diapause later in the season also show this trend. To better understand the effects of the timing of diapause initiation, we analyzed mRNA copy number of genes known to be involved in diapause regulation in early- and late-season diapausing ALCB that were overwintered in field conditions or using current agricultural management conditions. We hypothesized that overwintering conditions for late diapausing bees also affects gene expression profiles. Our results showed that expression profiles were altered by both overwintering condition and timing of diapause initiation, with bees that entered diapause earlier in the season showing different expression patterns than those that entered diapause later in the season. This trend was seen in expression of members of the cyclin family and several targets of the insulin signaling pathway, including forkhead box protein O (FOXO), which is known to be important for diapause regulation and stress responses. But, of the genes screened, the proto-oncogene, Myc, was the most impacted by the timing of diapause initiation. Under fluctuating temperatures there was significant differences in Myc expression between the early and late season samples in all months except for November and February. This same general trend in Myc expression was also seen in the laboratory-maintained bees with significant difference in expression in all months except for November, February, and May. These results support previous conclusions from our research showing that the molecular regulation of diapause development in ALCB is not a simple singular cascade of gene expression but a highly plastic response that varies between bees depending upon their environmental history.

opencc-by-4.0Apr 2022View details →

Akt inhibitor and Tacrolimus arrange apoptotic gene expression levels in MCF7 cells

Apoptosis balances the cells produced as a result of cell division and controls the differentiation in general tissue homeostatic mechanisms. It is known that apoptosis is a gene-oriented program and has effects on cell proliferation and differentiation by regulating several pro-apoptotic and anti-apoptotic gene families. In this study we investigated gene expression levels of tumor suppressor gene p53, survival protein and growth factor receptor PDGFRβ, anti-apoptotic protein NFκβ, pro-apoptotic proteins Bax and Caspase 9. According to our gene expression results, we showed that levels of p53, Bax and Caspase 9 in MCF7 cells were increased with Akt inhibitor application. Previous studies have reported that Akt inhibitor induces apoptosis by expressing these genes. Also our NFκB gene expression results support these findings. This effect of the Akt inhibitor shows that the PI3K/Akt/mTOR signaling pathway is one of the primary effective routes on apoptosis in MCF7 cells. It was observed that FK506 administration with Akt inhibitor contributed positively in favor of apoptosis in all parameters, although alone treatment FK506 showed no increase as Akt inhibitor in p53, Bax and Caspase 9 expression. This effect of FK506 showed that the Calcineurin/NFAT pathway is a secondary effective route on apoptosis. However, this positive effect of the co-administration of FK506 with Akt inhibitor on breast cancer gives us important clues for our subsequent studies. When we evaluated our findings of apoptosis and gene expression, it was observed that the combined treatment of the FK506 and Akt inhibitor, which did not show much effect alone, was highly effective and promising in reducing cancer proliferation and regulating apoptotic genes. These results indicate that the intracellular pathways which are used by the cancer act together and support each other.

opencc-by-4.0Apr 2022View details →

S1_The_differentially_expressed_genes_enriched_in_GO_clusters

This is supporting information to the article Downregulation of ammonium uptake improves the growth and tolerance of Kluyveromyces marxianus at high temperature, which has been submitted to MicrobiologyOpen.

opencc-zeroApr 2022View details →

Trachemys scripta gene expression data under constant and fluctuating incubation temperatures

There is ample research demonstrating that temperature can have complex effects on biological processes, including the timing of when organisms respond to temperature; some responses occur rapidly while others require an extended exposure time. However, most of what we know about temperature effects comes from studies using constant temperature conditions, which are not reflective of natural, fluctuating temperatures. Species with temperature-dependent sex determination (TSD) present an ideal system to study the temporal aspects of the temperature response because prior research has established a number of temperature-responsive genes involved in TSD, albeit under constant temperatures. To investigate potential differences in the timing of sexual development between constant and fluctuating incubation temperatures, we exposed Trachemys scripta embryos to two conditions that produce males (constant 26°C and 26 ± 3°C) and two that produce females (constant 31°C and 31 ± 3°C), and sampled embryonic gonads for gene expression analysis via qPCR.We analyzed three genes involved in testis differentiation (Kdm6b, Dmrt1, and Sox9) and two genes involved in ovary differentiation (Foxl2 and Cyp19A1). Results show that Kdm6b expression was significantly lower under fluctuating temperatures compared to constant temperatures. Foxl2 and Cyp19A1 expression were also lower under fluctuating temperatures, but not at all stages of development. These results suggest that constant temperatures caused increases in both Foxl2 and Cyp19A1 expression earlier (developmental stage 20) than fluctuating temperatures (stages 22 and 23). Dmrt1 and Sox9 expression did not differ between constant and fluctuating temperatures. These results highlight that not all genes in a temperature-dependent process respond to temperature in the same manner. Whether there are functional consequences of this variation remains to be determined.

opencc-zeroMay 2022View details →

Impacts of seasonality on gene expression in the Chinese Horseshoe Bat

Seasonality can cause changes in many environmental factors which potentially affects gene expression. Here, we used a bat species (Rhinolophus sinicus) from eastern China as a model to explore the molecular mechanisms of seasonal effects, in particular during phenological shifts in the spring and autumn. Based on the analysis of 45 RNA-seq samples, we found strong seasonal effects on gene expression, with a large number of genes identified as either specific or biased to each season. Weighted gene co-expression network analysis also identified multiple modules significantly associated with each season. These seasonal genes were further enriched into different functional categories. Consistent with effects of phenological shifts on bats, we found that genes related to promoting food intake were highly expressed in both autumn and spring. In addition, immunity genes were also highly expressed in both seasons although this seasonal immune response had tissue specificity in different seasons. In female bats, genes related to the delay of ovulation (e.g. NPPC, natriuretic peptide precursor type C) were highly expressed in October, while genes associated with the promotion of reproduction (e.g. DIO2, iodothyronine deiodinase 2) were biasedly expressed in April. Lastly, we found multiple known core clock genes in both October-biased and April-biased expressed genes, which may be involved in regulating the start and end of hibernation, respectively. Overall, together with studies in other land and aquatic animals, our work supports that seasonal gene expression variations may be a general evolutionary response to environmental changes in wild animals.

opencc-zeroJun 2022View details →

Tables of microRNA and gene expression of an echolocating bat

MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression and play key roles in many biological processes, such as development and response to multiple stresses. However, little is known about their roles in generating novel phenotypes and phenotypic variation during the course of animal evolution. Here, we, for the first time, characterized the miRNAs of the cochlea in an echolocating bat (Rhinolophus affinis). We sampled eight individuals from two R. affinis subspecies with significant echolocation call frequency differences. We identified 365 miRNAs and 121 of them were novel. By searching sequences of these miRNAs precursors in multiple high-quality mammal genomes, no specific miRNAs were found to be shared by all echolocating mammals. Together with the matched mRNA-seq data, we identified 1,766 differentially expressed genes (DEGs) between the two subspecies and 555 of them were negatively regulated by differentially expressed miRNAs (DEMs). We found that almost half of known hearing genes in the list of all DEGs were regulated negatively by DEMs, suggesting an important role of miRNAs in call frequency variation of the two subspecies. These targeted DEGs included several important hearing genes (e.g. Piezo1, Piezo2 and CDH23) that have been shown to be important in ultrasonic hearing of echolocating mammals.

MicroRNA-574-5p targeting HOXC6 expression inhibits the hepatocyte lipid uptake to alleviate NAFLD

In recent times, the non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. Increasing evidence supports the role of miRNAs in the pathogenesis of NAFLD. The miR-574-5p has been shown to be involved in lipid metabolism. However, studies on the correlation between miR-574-5p and NAFLD are lacking. Hence, in this study, we wanted to investigate whether miR-574-5p is associated with the pathogenesis of NAFLD. Through various in vivo and in vitro experiments, we found that miR-574-5p can inhibit lipid accumulation and lipid formation by targeting the HOXC6 3' UTR. We believe that our study makes a significant contribution to the literature because this study is the first to show that miR-574-5p is downregulated in liver tissue in a mouse NAFLD model. Further, understanding the miRNAs and their targets that regulate NAFLD may help us better understand the disease and lead to the design of a potential therapeutic against NAFLD in the future.In recent times, the non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. Increasing evidence supports the role of miRNAs in the pathogenesis of NAFLD. The miR-574-5p has been shown to be involved in lipid metabolism. However, studies on the correlation between miR-574-5p and NAFLD are lacking. Hence, in this study, we wanted to investigate whether miR-574-5p is associated with the pathogenesis of NAFLD. Through various in vivo and in vitro experiments, we found that miR-574-5p can inhibit lipid accumulation and lipid formation by targeting the HOXC6 3' UTR. We believe that our study makes a significant contribution to the literature because this study is the first to show that miR-574-5p is downregulated in liver tissue in a mouse NAFLD model. Further, understanding the miRNAs and their targets that regulate NAFLD may help us better understand the disease and lead to the design of a potential therapeutic against NAFLD in the future.

Results from "The Effects of Nonlinear Signal on Expression-Based Prediction Performance"

This zipped archive contains the result files from running the pipeline described in the manuscript "The Effects of Nonlinear Signal on Expression-Based Prediction Performance".

Input data from "The Effects of Nonlinear Signal on Expression-Based Prediction Performance"

These files are a 1GB fragments of a compressed archive containing the data used in the manuscript "The Effects of Nonlinear Signal on Expression-Based Prediction Performance". To simplify the uploading process, the file was split into chunks using the `split` utility in Linux. They can be joined back together with the command `cat input_data* > input_data.tar.gz` All data used is either publicly available or generated by this project. The subsets of the Recount3 and GTEx that we used are not owned by us, so putting them in this creative commons repository should not be construed as re-licensing them.

Model weights from "The Effects of Nonlinear Signal on Expression-Based Prediction Performance"

This file stores a representative set of saved models from the manuscript "The Effects of Nonlinear Signal on Expression-Based Prediction Performance".  To simplify the uploading process, the file was split into chunks using the `split` utility in Linux. They can be joined back together with the command `cat model_weights* > model_weights.tar.gz` These saved files correspond to the weights and optimizer state of models trained on various biological tasks. They can be "rehydrated" using the `load_model` function of the associated model class from this repo: https://github.com/greenelab/linear_signal

On taming the effect of transcript level intra-condition count variation during differential expression analysis: a story of dogs, foxes and wolves: Bowtie2 counts and kallisto abundances

Intra [1] and inter [2-5] study RNA-seq read datasets representing the varying brain compartments of foxes (n=24), as well as dogs (n=14) and wolves (n=6), as described in Lobo et al., (2022) (under review), were mapped to the dog reference transcriptome [6], which contained 26,107 annotated transcripts (Ensembl CanFam3.1, release 92) [7], using Bowtie2 v.2.3.4.1 [8] and using kallisto v0.46.1 [9]. Count data obtained following each mapping approach for each dataset had high correlations (Lobo et al., Figure S2). Bowtie2 counts were subsequently used in multiple differential analysis experiments in order to explore the effects of intra-condition count variation on the detection of differentially expressed transcripts. The individual count and abundance datasets for each corresponding RNA-seq dataset are available here.   A preprint of Lobo et al., 2022, currently under review for PLOS ONE, is available [10]. The preprint however does not contain reviewer requested information on simulations as this, along with other additions including an additional author RL, has been subsequently added during the review process. These additions will be made available following review via a link to the final paper.    Related software to this project are: 1. <a href="http://sourceforge.net/projects/cstone/">CStone</a>  2. <a href="http://sourceforge.net/projects/csreadgen/">CSReadGen</a> 3. <a href="https://sourceforge.net/projects/cview/">CView</a>  4. <a href="https://sourceforge.net/projects/chimsim/">ChimSim</a> 5. <a href="https://sourceforge.net/projects/tvscript/">TVScript</a> <   General details of the projects involved are available: <a href="https://cibio.up.pt/en/projects/is-hybridization-between-wolves-and-dogs-shaping-the-evolutionary-trajectory-of-wolf-populations-in-human-dominated-landscapes/">dog-wolf</a> and <a href="https://cibio.up.pt/en/projects/de-novo-based-sequence-assembly-of-next-generation-sequence-data-without-chimeras-improved-annotation-gene-expression-profiles-and-haplotype-br-reconstruction/">chimerism</a>.   References 1. Wang X, Pipes L, Trut L, Herbeck Y, Vladimirova A, Gulevich R, et al. Genomic responses to selection for tame/aggressive behaviors in the silver fox (Vulpes vulpes). Proc Natl Acad Sci. 2018;115: 10398–10403. doi:10.1073/pnas.1800889115   2. Roy M, Kim N, Kim K, Chung WH, Achawanantakun R, Sun Y, et al. Analysis of the canine brain transcriptome with an emphasis on the hypothalamus and cerebral cortex. Mamm Genome. 2013;24: 484–499. doi:10.1007/s00335-013-9480-0   3. Fushan AA, Turanov AA, Lee SG, Kim EB, Lobanov A V, Yim SH, et al. Gene expression defines natural changes in mammalian lifespan. Aging Cell. 2015;14: 352–365. doi:10.1111/acel.12283   4. Hoeppner MP, Lundquist A, Pirun M, Meadows JRS, Zamani N, Johnson J, et al. An improved canine genome and a comprehensive catalogue of coding genes and non-coding transcripts. PLoS One. 2014;9(3):91172. doi:10.1371/journal.pone.0091172   5. Albert FW, Somel M, Carneiro M, Aximu-Petri A, Halbwax M, Thalmann O, et al. A Comparison of Brain Gene Expression Levels in Domesticated and Wild Animals. Akey JM, editor. PLoS Genet. 2012;8:e1002962. doi:10.1371/journal.pgen.1002962   6. Hoeppner MP, Lundquist A, Pirun M, Meadows JRS, Zamani N, Johnson J, et al. An improved canine genome and a comprehensive catalogue of coding genes and non-coding transcripts. PLoS One. 2014;9(3):91172. doi:10.1371/journal.pone.0091172   7. Yates AD, Achuthan P, Akanni W, Allen J, Allen J, Alvarez-Jarreta J, et al. Ensembl 2020. Nucleic Acids Res. 2020;48: D682–D688. doi:10.1093/NAR/GKZ966   8. Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012. doi:10.1038/nmeth.1923   9. Bray NL, Pimentel H, Melsted P, Pachter L. Near-optimal probabilistic RNA-seq quantification. Nat Biotechnol 2016 345. 2016;34: 525–527. doi:10.1038/nbt.3519   10. Lobo D, Godinho R, Archer JP. On taming the effect of transcript level intra-condition count variation during differential expression analysis: a story of dogs, foxes and wolves. bioRxiv. 2022; 2022.01.24.477470. doi:10.1101/2022.01.24.477470