cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.12851864
title: Position of Deltaproteobacteria Cas12e nuclease cleavage sites depends on spacer length of guide RNA

description: Cas12e proteins (formerly CasX) form a distinct subtype of Class II type V CRISPR-Cas effectors. Recently, it was shown that DpbCas12e from <i>Deltaproteobacteria</i> and PlmCas12e from <i>Planctomycetes</i> can introduce programmable double-stranded breaks in mammalian genomes. Thus, along with Cas9 and Cas12a Class II effectors, Cas12e could be harnessed for genome editing and engineering. The location of cleavage points in DNA targets is important for application of Cas nucleases in biotechnology. DpbCas12e was reported to produce extensive 5ʹ-overhangs at cleaved targets, which can make it superior for some applications. Here, we used high throughput sequencing to precisely map the DNA cut site positions of DpbCas12e on several DNA targets. In contrast to previous observations, our results demonstrate that DNA cleavage pattern of Cas12e is very similar to that of Cas12a: DpbCas12e predominantly cleaves DNA after nucleotide position 17–19 downstream of PAM in the non-target DNA strand, and after the 22<sup>nd</sup> position of target strand, producing 3–5 nucleotide-long 5ʹ-overhangs. We also show that reduction of spacer sgRNA sequence from 20nt to 16nt shifts Cas12e cleavage positions on the non-target DNA strand closer to the PAM, producing longer 6–8nt 5ʹ-overhangs. Overall, these findings advance the understanding of Cas12e endonucleases and may be useful for developing of DpbCas12e-based biotechnology instruments.
DOI: 10.6084/m9.figshare.12851849
title: Competitive learning suggests circulating miRNA profiles for cancers decades prior to diagnosis

description: MicroRNAs are regulators of gene expressionand may be key markers in liquid biopsy.Early diagnosis is an effective means to increase patients’ overall survival. We generated genome-wide miRNA profiles from serum of patients and controls from the population-based Janus Serum Bank (JSB) and analysed them by bioinformatics and artificial intelligence approaches. JSB contains sera from 318,628 originally healthy persons, more than 96,000 of whom developed cancer. We selected 210 serum samples from patients with lung, colon or breast cancer at three time points prior to diagnosis (up to 32 years prior to diagnosis with median 5 years interval between TPs), one time-point after diagnosis and from individually matched controls. The controls were matched on age and year of all pre-diagnostic sampling time-points for the corresponding case. Using ANOVA we report 70 significantly deregulated markers (adjusted p-value&lt;0.05). The driver for the significance was the diagnostic time point (miR-575, miR-6821-5p, miR-630 with adjusted p-values&lt;10<sup>−10</sup>). Further, 91miRNAs were differently expressed in pre-diagnostic samples as compared to controls (nominal p
DOI: 10.6084/m9.figshare.12851897.v1
title: Comparative analysis of long noncoding RNAs in long-lived mammals provides insights into natural cancer-resistance

description: Mouse and rats are staple model organisms that have been traditionally used for oncological studies; however, their short lifespan and highly prone to cancers limit their utilizationsin understanding the mechanisms of cancer resistance. In recent years, several studies of the non-standard long-lived mammalian species like naked mole rat (NMR) have provided new insights of mechanisms in natural anti-cancer. How long-lived species genetically maintain longevity and cancer-resistance remains largely elusive. To better understand the underlying anti-cancer mechanisms in long-lived mammals, we genome widely identified long noncoding RNA (lncRNA) transcripts of two longevous mammals, bowhead whale (BW, <i>Balaena mysticetus</i>) and Brandt’s bat (BB, <i>Myotis brandtii</i>) and featured their sequence traits, expression patterns, and their correlations with cancer-resistance. Similar with naked mole rat (NMR, <i>Heterocephalus glaber</i>), the most long-lived rodent, BW and BB lncRNAs show low sequence conservation and dynamic expressions among tissues and physiological stages. By utilizing k-mers clustering, 75–136 of BW, BB and NMR lncRNAs were found in close relation (Pearson’s <i>r</i> ≥0.9, p r &gt; 0.8 or <i>r</i> <b>Abbreviations:</b> BW: bowhead whale; BB: Brandt’s bat; NMR: naked mole rat; LLM: long-lived mammal; HTS: human tumour-suppressors; PTS: potential tumour suppressor; ARD: ageing related diseases; HAR-Lncs: lncRNAs that related with human ageing diseases; Kmer-lncs: lncRNAs in long-lived mammal species that corelated (Pearson’s<i>r</i> ≥0.9, p &lt; 0.01) with the 10 HAR-Lncs by k-mers clustering; All-lncs: all the lncRNAs in long-lived mammal species; SDE-lncs: significant differentially expressed lncRNAs
DOI: 10.6084/m9.figshare.12851934
title: Novel, abundant Drosha isoforms are deficient in miRNA processing in cancer cells

description: MicroRNAs (miRNAs) are a class of small noncoding RNAs about 22-nucleotide (nt) in length that collectively regulate more than 60% of coding genes. Aberrant miRNA expression is associated with numerous diseases, including cancer. miRNA biogenesis is licenced by the ribonuclease (RNase) III enzyme Drosha, the regulation of which is critical in determining miRNA levels. We and others have previously revealed that alternative splicing regulates the subcellular localization of Drosha. To further investigate the alternative splicing landscape of Drosha transcripts, we performed PacBio sequencing in different human cell lines. We identified two novel isoforms resulting from partial intron-retention in the region encoding the Drosha catalytic domain. One isoform (AS27a) generates a truncated protein that is unstable in cells. The other (AS32a) produces a full-length Drosha with a 14 amino acid insertion in the RIIID domain. By taking advantage of Drosha knockout cells in combination with a previously established reporter assay, we demonstrated that Drosha-AS32a lacks cleavage activity. Furthermore, neither Drosha-27a nor Drosha-32a were able to rescue miRNA expression in the Drosha knockout cells. Interestingly, both isoforms were abundantly detected in a wide range of cancer cell lines (up to 15% of all Drosha isoforms). Analysis of the RNA-seq data from over 1000 breast cancer patient samples revealed that the AS32a is relatively more abundant in tumours than in normal tissue, suggesting that AS32a may play a role in cancer development.
DOI: 10.6084/m9.figshare.12851934.v1
title: Novel, abundant Drosha isoforms are deficient in miRNA processing in cancer cells

description: MicroRNAs (miRNAs) are a class of small noncoding RNAs about 22-nucleotide (nt) in length that collectively regulate more than 60% of coding genes. Aberrant miRNA expression is associated with numerous diseases, including cancer. miRNA biogenesis is licenced by the ribonuclease (RNase) III enzyme Drosha, the regulation of which is critical in determining miRNA levels. We and others have previously revealed that alternative splicing regulates the subcellular localization of Drosha. To further investigate the alternative splicing landscape of Drosha transcripts, we performed PacBio sequencing in different human cell lines. We identified two novel isoforms resulting from partial intron-retention in the region encoding the Drosha catalytic domain. One isoform (AS27a) generates a truncated protein that is unstable in cells. The other (AS32a) produces a full-length Drosha with a 14 amino acid insertion in the RIIID domain. By taking advantage of Drosha knockout cells in combination with a previously established reporter assay, we demonstrated that Drosha-AS32a lacks cleavage activity. Furthermore, neither Drosha-27a nor Drosha-32a were able to rescue miRNA expression in the Drosha knockout cells. Interestingly, both isoforms were abundantly detected in a wide range of cancer cell lines (up to 15% of all Drosha isoforms). Analysis of the RNA-seq data from over 1000 breast cancer patient samples revealed that the AS32a is relatively more abundant in tumours than in normal tissue, suggesting that AS32a may play a role in cancer development.
DOI: 10.6084/m9.figshare.12851897
title: Comparative analysis of long noncoding RNAs in long-lived mammals provides insights into natural cancer-resistance

description: Mouse and rats are staple model organisms that have been traditionally used for oncological studies; however, their short lifespan and highly prone to cancers limit their utilizationsin understanding the mechanisms of cancer resistance. In recent years, several studies of the non-standard long-lived mammalian species like naked mole rat (NMR) have provided new insights of mechanisms in natural anti-cancer. How long-lived species genetically maintain longevity and cancer-resistance remains largely elusive. To better understand the underlying anti-cancer mechanisms in long-lived mammals, we genome widely identified long noncoding RNA (lncRNA) transcripts of two longevous mammals, bowhead whale (BW, <i>Balaena mysticetus</i>) and Brandt’s bat (BB, <i>Myotis brandtii</i>) and featured their sequence traits, expression patterns, and their correlations with cancer-resistance. Similar with naked mole rat (NMR, <i>Heterocephalus glaber</i>), the most long-lived rodent, BW and BB lncRNAs show low sequence conservation and dynamic expressions among tissues and physiological stages. By utilizing k-mers clustering, 75–136 of BW, BB and NMR lncRNAs were found in close relation (Pearson’s <i>r</i> ≥0.9, p r &gt; 0.8 or <i>r</i> <b>Abbreviations:</b> BW: bowhead whale; BB: Brandt’s bat; NMR: naked mole rat; LLM: long-lived mammal; HTS: human tumour-suppressors; PTS: potential tumour suppressor; ARD: ageing related diseases; HAR-Lncs: lncRNAs that related with human ageing diseases; Kmer-lncs: lncRNAs in long-lived mammal species that corelated (Pearson’s<i>r</i> ≥0.9, p &lt; 0.01) with the 10 HAR-Lncs by k-mers clustering; All-lncs: all the lncRNAs in long-lived mammal species; SDE-lncs: significant differentially expressed lncRNAs
DOI: 10.5880/sfb806.66
title: Hydroclimate changes in eastern Africa over the past 200,000 years may have influenced early human dispersal

description: Reconstructions of climatic and environmental conditions can contribute to current debates about the factors that influenced early human dispersal within and beyond Africa. Here we analyse a 200,000-year multi-proxy paleoclimate record from Chew Bahir, a tectonic lake basin in the southern Ethiopian rift. Our record reveals two modes of climate change, both associated temporally and regionally with a specific type of human behaviour. The first is a long-term trend towards greater aridity between 200,000 and 60,000 years ago, modulated by precession-driven wet-dry cycles. Here, more favourable wetter environmental conditions may have facilitated long-range human expansion into new territory, while less favourable dry periods may have led to spatial constriction and isolation of local human populations. The second mode of climate change observed since 60,000 years ago mimics millennial to centennial-scale Dansgaard-Oeschger cycles and Heinrich events. We hypothesize that human populations may have responded to these shorter climate fluctuations with local dispersal between montane and lowland habitats.
DOI: 10.6084/m9.figshare.10084625
title: Root-associated fungal community reflects host spatial co-occurrence patterns in a subtropical forest

description: OTU tables, representative OTUs, and custom R codes that were used to explore the host-dependent differentiation of the root-associated fungal communities for 39 plant species in a subtropical forest.
DOI: 10.6084/m9.figshare.10084625.v5
title: Root-associated fungal community reflects host spatial co-occurrence patterns in a subtropical forest

description: OTU tables, representative OTUs, and custom R codes that were used to explore the host-dependent differentiation of the root-associated fungal communities for 39 plant species in a subtropical forest.
DOI: 10.6084/m9.figshare.10084625.v4
title: Root-associated fungal community as a host-dependent feature reflects plant spatial co-occurrence patterns in a subtropical forest

description: OTU tables, representative OTUs, and custom R codes that were used to explore the host-dependent differentiation of the root-associated fungal communities for 39 plant species in a subtropical forest.
DOI: 10.6084/m9.figshare.12851879.v1
title: Targeted RNA sequencing enhances gene expression profiling of ultra-low input samples

description: RNA-seq is the standard method for profiling gene expression in many biological systems. Due to the wide dynamic range and complex nature of the transcriptome, RNA-seq provides an incomplete characterization, especially of lowly expressed genes and transcripts. Targeted RNA sequencing (RNA CaptureSeq) focuses sequencing on genes of interest, providing exquisite sensitivity for transcript detection and quantification. However, uses of CaptureSeq have focused on bulk samples and its performance on very small populations of cells is unknown. Here we show CaptureSeq greatly enhances transcriptomic profiling of target genes in ultra-low-input samples and provides equivalent performance to that on bulk samples. We validate the performance of CaptureSeq using multiple probe sets on samples of iPSC-derived cortical neurons. We demonstrate up to 275-fold enrichment for target genes, the detection of 10% additional genes and a greater than 5-fold increase in identified gene isoforms. Analysis of spike-in controls demonstrated CaptureSeq improved both detection sensitivity and expression quantification. Comparison to the CORTECON database of cerebral cortex development revealed CaptureSeq enhanced the identification of sample differentiation stage. CaptureSeq provides sensitive, reliable and quantitative expression measurements on hundreds-to-thousands of target genes from ultra-low-input samples and has the potential to greatly enhance transcriptomic profiling when samples are limiting.
DOI: 10.6084/m9.figshare.12851888.v1
title: Linking the association between circRNAs and Alzheimer’s disease progression by multi-tissue circular RNA characterization

description: Alzheimer’s disease (AD) has devastating consequences for patients during its slow, progressive course. It is important to understand the pathology of AD onset. Recently, circular RNAs (circRNAs) have been found to participate in many human diseases including cancers and neurodegenerative conditions. In this study, we mined the published dataset on the AMP-AD Knowledge Portal from the Mount Sinai Brain Bank (MSBB) to describe the circRNA profiles at different AD stages in brain samples from four brain regions: anterior prefrontal cortex, superior temporal lobe, parahippocampal gyrus and inferior frontal gyrus. In total, we found 147 circRNAs to be differentially expressed (DE) for different AD severity levels in the four regions. We also characterized the mRNA-circRNA co-expression network and annotated the potential function of circRNAs based on the co-expressed modules. Based on our results, we found that the most circRNA-regulated region in AD patients with severe symptoms was the parahippocampal gyrus. The strongest negatively AD severity-correlated module in the parahippocampal gyrus was enriched in cognitive disability and pathological-associated pathways such as synapse organization and regulation of membrane potential. Finally, a regression model based on the expression pattern of DE circRNAs in the module could help to distinguish the disease severity of patients, further supporting a role for circRNAs in AD pathology. In conclusion, our findings indicate that circRNAs in parahippocampal gyrus are possible biomarkers and regulators of AD as well as potential therapeutic targets.
DOI: 10.6084/m9.figshare.12851879
title: Targeted RNA sequencing enhances gene expression profiling of ultra-low input samples

description: RNA-seq is the standard method for profiling gene expression in many biological systems. Due to the wide dynamic range and complex nature of the transcriptome, RNA-seq provides an incomplete characterization, especially of lowly expressed genes and transcripts. Targeted RNA sequencing (RNA CaptureSeq) focuses sequencing on genes of interest, providing exquisite sensitivity for transcript detection and quantification. However, uses of CaptureSeq have focused on bulk samples and its performance on very small populations of cells is unknown. Here we show CaptureSeq greatly enhances transcriptomic profiling of target genes in ultra-low-input samples and provides equivalent performance to that on bulk samples. We validate the performance of CaptureSeq using multiple probe sets on samples of iPSC-derived cortical neurons. We demonstrate up to 275-fold enrichment for target genes, the detection of 10% additional genes and a greater than 5-fold increase in identified gene isoforms. Analysis of spike-in controls demonstrated CaptureSeq improved both detection sensitivity and expression quantification. Comparison to the CORTECON database of cerebral cortex development revealed CaptureSeq enhanced the identification of sample differentiation stage. CaptureSeq provides sensitive, reliable and quantitative expression measurements on hundreds-to-thousands of target genes from ultra-low-input samples and has the potential to greatly enhance transcriptomic profiling when samples are limiting.
DOI: 10.6084/m9.figshare.12851888
title: Linking the association between circRNAs and Alzheimer’s disease progression by multi-tissue circular RNA characterization

description: Alzheimer’s disease (AD) has devastating consequences for patients during its slow, progressive course. It is important to understand the pathology of AD onset. Recently, circular RNAs (circRNAs) have been found to participate in many human diseases including cancers and neurodegenerative conditions. In this study, we mined the published dataset on the AMP-AD Knowledge Portal from the Mount Sinai Brain Bank (MSBB) to describe the circRNA profiles at different AD stages in brain samples from four brain regions: anterior prefrontal cortex, superior temporal lobe, parahippocampal gyrus and inferior frontal gyrus. In total, we found 147 circRNAs to be differentially expressed (DE) for different AD severity levels in the four regions. We also characterized the mRNA-circRNA co-expression network and annotated the potential function of circRNAs based on the co-expressed modules. Based on our results, we found that the most circRNA-regulated region in AD patients with severe symptoms was the parahippocampal gyrus. The strongest negatively AD severity-correlated module in the parahippocampal gyrus was enriched in cognitive disability and pathological-associated pathways such as synapse organization and regulation of membrane potential. Finally, a regression model based on the expression pattern of DE circRNAs in the module could help to distinguish the disease severity of patients, further supporting a role for circRNAs in AD pathology. In conclusion, our findings indicate that circRNAs in parahippocampal gyrus are possible biomarkers and regulators of AD as well as potential therapeutic targets.
DOI: 10.5281/zenodo.4744544
title: The Influence of Dune Aspect Ratio, Beach Width and Storm Characteristics on Dune Erosion for Managed and Unmanaged Beaches Data

description: Data associated with "The Influence of Dune Aspect Ratio, Beach Width and Storm Characteristics on Dune Erosion for Managed and Unmanaged Beaches"
DOI: 10.5281/zenodo.4059884
title: The Influence of Dune Aspect Ratio, Beach Width and Storm Characteristics on Dune Erosion for Managed and Unmanaged Beaches Data

description: Data associated with "The Influence of Dune Aspect Ratio, Beach Width and Storm Characteristics on Dune Erosion for Managed and Unmanaged Beaches"
DOI: 10.5281/zenodo.4744548
title: Actenoides lindsayi SPAdes preassembly

description: .
DOI: 10.5281/zenodo.4744547
title: Actenoides lindsayi SPAdes preassembly

description: .
DOI: 10.5281/zenodo.4744557
title: Actinopyga echinites SPAdes preassembly

description: .
DOI: 10.5281/zenodo.4744556
title: Actinopyga echinites SPAdes preassembly

description: .
DOI: 10.7277/4e31-e757
title: Dataset Test

description: Test version 3 with location data update
DOI: 10.5281/zenodo.4744561
title: Adela reaumurella SPAdes preassembly

description: .
DOI: 10.5281/zenodo.4744560
title: Adela reaumurella SPAdes preassembly

description: .
DOI: 10.6084/m9.figshare.11855313
title: Analysis of Ras-effector interaction competition in large intestine and colorectal cancer context

description: Cancer is the second leading cause of death globally, and colorectal cancer (CRC) is among the five most common cancers. The small GTPase KRAS is an oncogene that is mutated in ~30% of all CRCs. Pharmacological treatments of CRC are currently unsatisfactory, but much hope rests on network-centric approaches to drug development and cancer treatment. These approaches, however, require a better understanding of how networks downstream of Ras oncoproteins are connected in a particular tissue context – here colon and CRC. Previously we have shown that competition for binding to a ‘hub’ protein, such as Ras, can induce a rewiring of signal transduction networks. In this study, we analysed 56 established and predicted effectors that contain a structural domain with the potential ability to bind to Ras oncoproteins and their link to pathways coordinating intestinal homoeostasis and barrier function. Using protein concentrations in colon tissue and Ras-effector binding affinities, a computational network model was generated that predicted how effectors differentially and competitively bind to Ras in colon context. The model also predicted both qualitative and quantitative changes in Ras-effector complex formations with increased levels of active Ras – to simulate its upregulation in cancer – simply as an emergent property of competition for the same binding interface on the surface of Ras. We also considered how the number of Ras-effector complexes at the membrane can be increased by additional domains present in some effectors that are recruited to the membrane in response to specific conditions (inputs/stimuli/growth factors) in colon context and CRC.
DOI: 10.6084/m9.figshare.11855313.v1
title: Analysis of Ras-effector interaction competition in large intestine and colorectal cancer context

description: Cancer is the second leading cause of death globally, and colorectal cancer (CRC) is among the five most common cancers. The small GTPase KRAS is an oncogene that is mutated in ~30% of all CRCs. Pharmacological treatments of CRC are currently unsatisfactory, but much hope rests on network-centric approaches to drug development and cancer treatment. These approaches, however, require a better understanding of how networks downstream of Ras oncoproteins are connected in a particular tissue context – here colon and CRC. Previously we have shown that competition for binding to a ‘hub’ protein, such as Ras, can induce a rewiring of signal transduction networks. In this study, we analysed 56 established and predicted effectors that contain a structural domain with the potential ability to bind to Ras oncoproteins and their link to pathways coordinating intestinal homoeostasis and barrier function. Using protein concentrations in colon tissue and Ras-effector binding affinities, a computational network model was generated that predicted how effectors differentially and competitively bind to Ras in colon context. The model also predicted both qualitative and quantitative changes in Ras-effector complex formations with increased levels of active Ras – to simulate its upregulation in cancer – simply as an emergent property of competition for the same binding interface on the surface of Ras. We also considered how the number of Ras-effector complexes at the membrane can be increased by additional domains present in some effectors that are recruited to the membrane in response to specific conditions (inputs/stimuli/growth factors) in colon context and CRC.