Find research datasets worth reusing

Massively parallel screens to identify splice disruptive variants in human disease genes

Splicing is a critical step in mRNA maturation with roles in gene regulation and proteome diversification. Splice disruptive variants (SDVs) are implicated in diverse human diseases, and 10-33% of exonic variants may disrupt splicing. However, identifying SDVs remains challenging due to the degeneracy and redundancy of the underlying sequence code. Experimental splicing measurements from patient cells or mini-gene assays can detect SDVs but have traditionally been low-throughput.  Massively parallel reporter assays (MPSAs) systematically measure splicing impacts at scale and could clarify variant pathogenicity and inform models of splicing regulation. In this assay, complex barcoded libraries of mutant exons are synthesized, cloned into minigene constructs, and transfected into human cells. Splicing outcomes of each mutation are quantified en masse using targeted RNA-seq of minigene-derived transcripts, and I developed custom python package to process the resulting data. In Chapter 2, I apply this assay to the pituitary transcription factor gene POU1F1 (in collaboration Dr. Sally Camper’s lab). Mutations in POU1F1 cause combined pituitary hormone deficiency (CPHD), a clinically and genetically heterogenous disorder with prevalence ~1:4000. We targeted exon 2, which has two alterative isoforms (alpha and beta) using competing splice acceptors that encode mutually antagonistic proteins. We measured the splicing effects of 1,070 SNVs across the exon and surrounding introns and identified 96 SDVs - 14 of which were synonymous substitutions. Our measurements were concordant with six nearby heterozygous missense and synonymous variants seen in unrelated hypopituitarism patients. This map identifies a putative splice silencer motif that represses the use of the normally lowly expressed beta isoform. In Chapter 3, I apply a MPSA to a critical developmental renal transcription factor gene, WT1 (in collaboration with clinical nephrologist Dr. Jen Lai Yee). Mutations in WT1 are implicated in nephrotic syndrome and sexual differentiation phenotypes. I focus on exon 9 which is alternatively spliced at competing donor sites resulting in two isoforms (KTS+ and KTS-). KTS+ and KTS- are normally expressed in ~2:1 ratio, but perturbation of the ratio can lead to Frasier’s syndrome – a rare nephrotic syndrome. We tested 518 SNVs for splicing defects and identified 8 known Frasier’s Syndrome variants as well as 16 additional variants that similarly lowered the KTS ratio. We also detected 19 variants increasing the KTS ratio - two of which have been observed in patients with sexual differentiation phenotypes. Although MPSAs can measure splicing effects of hundreds of variants simultaneously, the current scale of variant discovery via exome and genome sequencing demands efficient and accurate computational approaches to identify splice disruptive variants genome-wide. To evaluate the state of the art within contemporary splice prediction algorithms, in Chapter 4 I employed the results of five high throughput splicing assays and one literature curated variant set. A unique advantage of MPSAs over typical training and validation datasets is that they avoid bias towards essential splice site variants. I found the latest deep learning tools, SpliceAI and Pangolin, were most concordant with the measured splicing effects. However, all tools showed less agreement with exonic splicing outcomes compared to intronic. Some tools’ predictions, like SpliceAI’s, were sensitive to specified annotation files. Thus, there is still room for improvement within the next generation of splice prediction algorithms which future MPSA studies may facilitate.

Large-scale saliva pooling as a screening strategy to control transmission_raw data

This dataset include the raw data of our experience after building a bespoke laboratory to control critical areas by pooling samples of saliva. From August 2020 to February 2022; 928,528 individual self-samples of saliva were processed in 52,580 pools, 4,935 of which were positive and helped us detect 5,806 nonsymptomatic individuals.  The dataset was collected directly from the laboratory information system and was processed to delete the columns with sensitive information. The Dataset was charged as XLSX file and only need a compatible software. To facilitate the understanding of the data set, which uses the Galician language and an internal nomenclature of our laboratory, we include a sheet named "description" and a README file in which it defines the terms used and their equivalence with those used in the article.

Prevalence Of Sickle Cell Trait and Needs Assessment Forfor Uptake of Sickle Cell Screening Among Secondary School Students in Kampala City, Uganda

This study aimed to determine the burden of SCT and factors influencing uptake of screening services among secondary school students in Uganda. Data was collected using semi-structured questionnaires and analyzed using descriptive statistics and logistic regression.

opencc-zeroMay 2023View details →

dryad36/100

Burden of cardiometabolic risk factors and preclinical target organ damage among adults in Freetown, Sierra Leone: a community-based health-screening survey

The study aimed to investigate the prevalence of cardiometabolic risk factors (CMRFs), target organ damage and its associated factors among adults in Freetown, Sierra Leone. Design This community-based cross-sectional study used a stratified multistage random sampling method to recruit adult participants. Setting The health screening study was conducted between October 2019 and October 2021 in Western Area Urban, Freetown, Sierra Leone. Participants A total of 2394 adults Sierra Leoneans aged 20 years, or more were enrolled. Outcome measure Anthropometric data, fasting lipid profiles, fasting plasma glucose, target organ damage, clinical profiles and demographic characteristic of participants were described. The cardiometabolic risks were further related to target organ damage. Results The prevalence of known CMRFs was 35.3% for hypertension, 8.3% for diabetes mellitus, 21.1% for dyslipidemia, 10.0% for obesity, 13.4% for smoking and 37.9% for alcohol. Additionally, 16.1% had left ventricular hypertrophy (LVH) by ECG, 14.2% had LVH by 2D-Echo while 11.4% had chronic kidney disease. Diabetes [OR = 1.176, 95% C.I. (0.759 - 1.823)] and dyslipidaemia [OR = 1.844, 95% C.I. (1.006 -3.380)] were independently associated with LVH. LVH by Echo shows an independent association with diabetes mellitus [OR =1.176, 95% C.I (0.759-1.823)] and dyslipidemia [OR = 1.844, 95% C.I (1.006-3.380)]. The odds of having CKD were associated with diabetes mellitus [OR =1.212, 95% CI (0.741-1.983)] and hypertension [OR =1.163, 95% CI (0.887-1.525)]. A low optimal cut-off points for ECG-LVH (male 24.5 vs female 27.5mm) was required to maximize sensitivity and specificity. Conclusions This study provides novel data-driven information on the burden of cardiometabolic risks and its association with preclinical target organ damage in a resource limited setting. It illustrates the need for interventions in improve cardiometabolic health screening and management among adults in Sierra Leoneans.

opencc-by-4.0Jun 2023View details →

PIGNet2: A versatile deep learning-based protein-ligand interaction prediction model for accurate binding affinity scoring and virtual screening

Training and test datasets of the paper "Improving the versatility of deep learning-based protein-ligand interaction prediction for accurate binding affinity scoring and virtual screening".

Supplemental Datasets for 'Multiplexed effector screening for recognition by endogenous resistance genes using positive defense reporters in wheat protoplasts'

Supplemental Datasets:Number File name Description S1 S1_Figure1_Data.csv Luminescence data for Figure 1, protoplast time course experiment S2 S2_RNAseqSampleTable.csv List of samples and treatment groups for RNAseq experiment S3 S3_LFC_1_genes.xlsx Lists of Gabo/GaboSr50, Fielder and all cultivar genes upregulated by log fold threshold of 1 S4 S4_GOTerms_Table.xlsx GO terms analysis Query tables and g:profiler results tables S5 S5_LFC2_genes.xlsx Lists of Gabo/GaboSr50, Fielder and all cultivar genes upregulated by log fold threshold of 2  S6 S6_Primers.xlsx List of primers used S7 S7_PlasmidList.xlsx List of plasmids used S8 S8_Figures3-5Data.xlsx Luminescence data used for generating Figures 3 - 7S9 S9_Figures3-7Stat.xlsx Stats output for Figures 3 - 7 S10 S10_SuppFiguresData.xlsx Data for Supplementary Figures S1 and S2

opencc-by-4.0Jul 2023View details →

Trellis Single-Cell Screening Reveals Stromal Regulation of Patient-Derived Organoid Drug Responses

Patient-derived organoids (PDOs) can model personalized therapy responses, however current screening technologies cannot reveal drug response mechanisms or how tumor microenvironment cells alter therapeutic performance. To address this, we developed a highly-multiplexed mass cytometry platform to measure post translational modification (PTM) signaling, DNA-damage, cell-cycle activity, and apoptosis in >2,500 colorectal cancer (CRC) PDOs and cancer associated fibroblasts (CAFs) in response to clinical therapies at single-cell resolution. To compare patient- and microenvironment-specific drug responses in thousands of single-cell datasets, we developed Trellis — a highly-scalable, hierarchical tree-based treatment effect analysis method. Trellis single-cell screening revealed that on-target cell-cycle blockage and DNA-damage drug effects are common, even in chemorefractory PDOs. However, drug-induced apoptosis is rare, patient-specific, and aligns with cancer cell PTM signaling. We find that CAFs can regulate cancer cell plasticity — shifting proliferative stem cells to slow-cycling revival stem cells via YAP to protect cancer cells from chemotherapy.   This repo contains the processed scRNA-seq Scanpy AnnData objects generated from the study. More information describing the data can be found at: https://github.com/TAPE-Lab/Ramos-et-al-Trellis

opencc-by-4.0Jan 2021View details →

Supporting information from Prospective environmental risk screening of seven advanced materials based on production volumes and aquatic ecotoxicity

Supporting information (Opne data) for the publication Prospective environmental risk screening of seven advanced materials based on production volumes and aquatic ecotoxicity

opencc-by-4.0May 2022View details →

AsdKB: A Chinese Knowledge Base for the Early Screening and Diagnosis of Autism Spectrum Disorder

Instance <ul> <li>Instance triples</li> </ul> Mapping <ul> <li>mapping.owl: ontology mapping to UMLS and ADAR</li> </ul> Ontology <ul> <li>ontology.owl: AsdKB ontology</li> </ul> For more details, please refer to <a href="https://github.com/SilenceSnake/ASDKB">http://w3id.org/asdkb</a>

opencc-by-2.0Mar 2022View details →

LMW Binding Affinity Screen for TBXT

Uploaded excel spreadsheets contain the raw data for a SPR campaign targeting TBXT. The data was collected by HDBioscience and is made public by UNC-SGC, The Chordoma Foundation, The Mark Foundation for Cancer Research. If prompted "HDB" is the password for any Excel file. The "ID with Smiles" spreadsheet contains the corresponding SMILES for all the compounds screened.  -----  More SPR data has been uploaded from 20230103. This dataset has a tab with the SMILES.

opencc-by-4.0Aug 2023View details →

Identification of Potential JNK3 Inhibitors Through Virtual Screening, Molecular Docking And Molecular Dynamics Simulation as Therapeutics for Alzheimer's Disease

Alzheimer's disease (AD) is a complex neurological disorder without effective treatment. One factor in its development is c-Jun N-terminal kinases (JNKs), a type of protein related to brain function. JNK3, found mainly in the brain, contributes to AD by promoting brain abnormalities. Current research aims to create new JNK3 inhibitors for AD treatment using a virtual screening method. A database of compounds was filtered, and five potential compounds were identified with better scores than a reference. These compounds underwent simulations and energy calculations, showing stability and potential as JNK3 inhibitors.

dryad36/100

CRISPR/Cas9 screen for essential endolysosomal genes under free choline limitation

Lysosomes degrade macromolecules and recycle their nutrient content to support cell function and survival. Yet, the machineries involved in lysosomal recycling of many nutrients remain to be discovered, with a notable example being choline, an essential metabolite liberated via phospholipid degradation. Here, we engineered metabolic dependency on lysosome-derived choline in pancreatic cancer cells to perform an endolysosome-focused CRISPR-Cas9 screen for genes mediating lysosomal choline recycling. We identified the orphan lysosomal transmembrane protein SPNS1 as critical for cell survival under choline limitation. SPNS1 loss leads to intralysosomal accumulation of lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE). Mechanistically, we reveal that SPNS1 is a proton gradient-dependent transporter of LPC species from the lysosome for their re-esterification into phosphatidylcholine in the cytosol. Finally, we establish that LPC efflux by SPNS1 is required for cell survival under choline limitation. Collectively, our work defines a lysosomal phospholipid salvage pathway that is essential under nutrient limitation, and more broadly, provides a robust platform to deorphan lysosomal gene function.

opencc-zeroSep 2023View details →

opencc-by-4.0Oct 2023View details →

Images of plants at harvest timepoint of Mini5SynCom Screen and Validation Experiments

pictures of plants at harvest timepoint (14 days post infection) of all experiments and data shown in publication titled "Identifying microbiota community patterns important for plant protection using machine learning in synthetic community experiments" by B. Emmenegger, J. Massoni, C.M. Pestalozzi, M. Bortfeld-Miller, B.A. Maier and J.A. Vorholt. The picture name is unique to be able to link to data presented in supplemental data 1.

opencc-by-4.0Oct 2023View details →

Data supporting 'The Response of Midlatitude Surface Temperature Persistence to Arctic Sea-Ice Loss' by Neil T Lewis, William J M Seviour, Hannah E Roberts-Straw, and James A Screen.

Data supporting Lewis et al., 2023. The Response of Midlatitude Surface Temperature Persistence to Arctic Sea-Ice Loss. Submitted to Geophysical Research Letters.All model output is contained within the folder data/. All data is in NetCDF format.The folder data/PAMIP/ contains output from coupled AOGCMs that contributed piArcSIC and futArcSIC timeslice runs to PAMIP. The AOGCMS present are: HadGEM3-GC31-MM, IPSL-CM6A-LR, CESM2-WACCM6, and CESM-WACCM-SC. For each model + run, two data files are included. One contains the autocorrelation of surface temperature, at 5, 10, and 15 day lags. The second contains the frequency and duration of persistent extremes (as defined in Lewis et al., 2023).Additional output is included in data/PAMIP/ from extended pdSIC-ext and futArcSIC-ext experiments run using CNRM-CM6-1. For each run, a file containing the autocorrelation of surface temperature (as above) is included.The folder data/CMIP/ contains output from CMIP6 historical/SSP585 runs using three of the models listed above: HadGEM3-GC31-MM, IPSL-CM6A-LR, and CESM2-WACCM6. For each model, 'pre-industrial' and 'future' output is available. Output in these files was computed from 30-year time-periods, subsampled from the historical/SSP585 runs, selected so that the 30-year average sea-ice area matched that in the corresponding PAMIP runs above. For each model and time period, two data files are included. One contains the autocorrelation of surface temperature, at 5, 10, and 15 day lags. The second contains the frequency and duration of persistent extremes (as defined in Lewis et al., 2023).Output is also included in data/CMIP/ from CNRM-CM6-1 'present day' and 'future' time periods, selected to match the sea-ice area in the CNRM -ext PAMIP runs. For this model, output files contain the autocorrelation of surface temperaure.

restrictedIPD-UNDECIDEDFeb 2026View details →

Administration Method of Cognitive Screening in Older Individuals With Hearing Loss

ClinicalTrials.gov study NCT03402932. IPD Sharing: UNDECIDED. Countries: 1. Publications: 4.

closedIPD-NOFeb 2026View details →

A Minimally-Invasive Sponge on a String Device for Screening for Barrett's Esophagus

ClinicalTrials.gov study NCT02560623. IPD Sharing: NO. Countries: 1. Publications: 3.

restrictedIPD-UNDECIDEDFeb 2026View details →

Molecular Breast Imaging as a Screening Tool for Women With Dense Breasts

ClinicalTrials.gov study NCT00620373. IPD Sharing: Not stated. Countries: 1. Publications: 1.

controlledIPD-YESFeb 2026View details →

Mackenzie's Mission: The Australian Reproductive Carrier Screening Project

ClinicalTrials.gov study NCT04157595. IPD Sharing: YES. Countries: 1. Publications: 1.