Adjacent Sequences Research Articles

PKET-GCN: Prior knowledge enhanced time-varying graph convolution network for traffic flow prediction

Due to prediction on the traffic flow is influenced by the real environment and historical data, the produced traffic graph may include significant uncertainty. The graph convolution operation is widely used in traffic flow prediction with its effective modeling ability on graph structures. However, in this method, it ignores the roles of external factors and historical data from fixed period is used that inevitably will lead to exclusion of detailed dynamic spatial–temporal correlation. To this end, we propose a novel method based on prior knowledge enhanced time-varying graph convolution network (PKET-GCN). First, we characterize factors affecting the traffic flow into dynamic and static features. The dynamic features include data correlation and external interference, while the static features consist of physical distances. Then we design a prior knowledge based module to extract the correlation of nodes and combine it with graph convolution to obtain dynamic spatial features. Next, a time-varying feature extraction module is designed to derive dynamic and long-term temporal features from periodic and adjacent sequences. Finally, the projection module is established to fuse the multiple modules and give the prediction value. The experimental results on five real-world datasets indicate that PKET-GCN is more effective than several existing methods.

Detection of cancer-associated miRNA using a fluorescence switch of AgNC@NA and guanine-rich overhang sequences.

DNA-templated silver nanoclusters (AgNC@DNA) are a novel type of nanomaterial with advantageous optical properties. Only a few atoms in size, the fluorescence of nanoclusters can be tuned using DNA overhangs. In this study, we explored the properties of AgNCs manufactured on a short single-stranded (dC)12 when adjacent G-rich sequences (dGN , with N = 3-15) were added. The 'red' emission of AgNC@dC12 with λMAX = 660 nm dramatically changed upon the addition of a G-rich overhang with NG = 15. The pattern of the emission-excitation matrix (EEM) suggested the emergence of two new emissive states at λMAX = 575 nm and λMAX = 710 nm. The appearance of these peaks provides an effective way to design biosensors capable of detecting specific nucleic acid sequences with low fluorescence backgrounds. We used this property to construct an NA-based switch that brings AgNC and the G overhang near one another, turning 'ON' the new fluorescence peaks only when a specific miRNA sequence is present. Next, we tested this detection switch on miR-371, which is overexpressed in prostate cancer. The results presented provide evidence that this novel fluorescent switch is both sensitive and specific with a limit of detection close to 22 picomoles of the target miR-371 molecule.

Spatio-Temporal Transformer Recommender: Next Location Recommendation with Attention Mechanism by Mining the Spatio-Temporal Relationship between Visited Locations

Location-based social networks (LBSN) allow users to socialize with friends by sharing their daily life experiences online. In particular, a large amount of check-ins data generated by LBSNs capture the visit locations of users and open a new line of research of spatio-temporal big data, i.e., the next point-of-interest (POI) recommendation. At present, while some advanced methods have been proposed for POI recommendation, existing work only leverages the temporal information of two consecutive LBSN check-ins. Specifically, these methods only focus on adjacent visit sequences but ignore non-contiguous visits, while these visits can be important in understanding the spatio-temporal correlation within the trajectory. In order to fully mine this non-contiguous visit information, we propose a multi-layer Spatio-Temporal deep learning attention model for POI recommendation, Spatio-Temporal Transformer Recommender (STTF-Recommender). To incorporate the spatio-temporal patterns, we encode the information in the user’s trajectory as latent representations into their embeddings before feeding them. To mine the spatio-temporal relationship between any two visited locations, we utilize the Transformer aggregation layer. To match the most plausible candidates from all locations, we develop on an attention matcher based on the attention mechanism. The STTF-Recommender was evaluated with two real-world datasets, and the findings showed that STTF improves at least 13.75% in the mean value of the Recall index at different scales compared with the state-of-the-art models.

Identification of Protein-Coding Gene Structure and Protein-Related Genes and Their Splicing Sites in Kidney Stone Disease: A Protein Big Data Analysis.

The study of protein-coding gene structure and protein-related genes in kidney stone disease is used for accurate identification of splicing sites and accurate location of gene exon boundaries, which is one of the difficulties and key problems in understanding the genome and discovering new genes. Prediction techniques based on signal characteristics of conserved sequences around splicing sites, such as the weighted array model (WAM), are widely used. On this basis, several other features that can be used for splicing site recognition (such as the base composition of splicing site upstream and downstream sequences, the change of signal and base composition of upstream and downstream sequences with the C + G content of adjacent sequences) were mined further, and a model was developed to describe these features. In this study, a log-linear model that can effectively integrate these features for splicing site recognition was designed, and a SpliceKey programme was developed. The findings reveal that SpliceKey's splicing site identification accuracy is not only much better than the WAM approach, but also better than DGSplice.

Nanopore sequencing for N1-methylpseudouridine in RNA reveals sequence-dependent discrimination of the modified nucleotide triphosphate during transcription.

Direct RNA sequencing with a commercial nanopore platform was used to sequence RNA containing uridine (U), pseudouridine (Ψ)or N1-methylpseudouridine (m1Ψ) in>100 different 5-nucleotide contexts. The base calling data for Ψ or m1Ψ were similar but different from U allowing their detection. Understanding the nanopore signatures for Ψ and m1Ψ enabled a running start T7 RNA polymerase assay to study the selection of UTP versus ΨTP or m1ΨTP competing mixtures in all possible adjacent sequence contexts. A significant sequence context dependency was observed for T7 RNA polymerase with insertion yields for ΨTP versus UTP spanning a range of 20-65%, and m1ΨTP versus UTP producing variable yields that differ by 15-70%. Experiments with SP6 RNA polymerase, as well as chemically-modified triphosphates and DNA templates provide insight to explain the observations. The SP6 polymerase introduced m1ΨTP when competed with UTP with a smaller window of yields (15-30%) across all sequence contexts studied. These results may aid in future efforts that employ RNA polymerases to make therapeutic mRNAs with sub-stoichiometric amounts of m1Ψ.

Abstract A010: Deciphering molecular and cellular differences between black and white colorectal cancers through in-depth transcriptomic analyses

Abstract Background Compared to all other racial groups, black Americans are most likely to be diagnosed with colorectal cancer (CRC) and are most likely to die from the disease. These racial disparities have been largely attributed to social and economic conditions that impact the prevalence of co-morbidities and access to quality health care. However, the molecular and cellular differences in CRC tumors between black and white subjects remain largely uncharacterized. Methods We analyzed paired tumor and adjacent normal RNA sequencing reads collected from 15 black and 18 white subjects at Downstate Medical Center and Stony Brook University Hospital (DSSBU). 273 additional RNA sequencing and clinicopathologic data from The Cancer Genome Atlas (TCGA) were used as a validation cohort. In the TCGA dataset, 54 black subjects were propensity score matched to 108 white subjects by age, sex, tumor location and tumor stage. Differential expression analysis was performed with EdgeR and Wilcoxon rank-sum test, which was recently recommended for human population samples. Gene Ontology (GO) enrichment analysis of DEGs (absolute log 2-fold change > 1, adjust p value < 0.05) was performed using enrichR. Gene set enrichment analysis (GSEA) of hallmark gene sets was applied to the gene list ranked by fold changes. The TPM (transcript per million) data was used to estimate relative cell abundance via xCell. Antitumor immune response likelihood scores were generated via the Estimate Systems Immune Response (EaSIeR) R package. Results EdgeR analysis identified 15 and 80 DEGs in the DSSBU and TCGA datasets, respectively. Two DEGs, CXCL10 and RPPH1 have decreased expression while EEF1A1P13 has higher expression in black samples from both datasets. CXCL10 remained a DEG under the Wilcoxon test in the TCGA dataset and in propensity score matched samples. GO enrichment analysis identified “Chemokine-mediated signaling pathway” as a significantly different biological process between tumor groups with a FDR of 0.043 and 0.0004 in TCGA and DSSBU respectively. GSEA computed a negative enrichment score for IL6 JAK STAT3 signaling, Interferon alpha response, Interferon gamma response, Allograft rejection and Myc targets V1 in the black group from both datasets. xCell analysis of the DSSBU data revealed significant enrichment for endothelial cells, adipocytes and hematopoietic stem cells in black tumor samples, while white samples were significantly enriched for basophils, T helper 2 cells and common lymphoid progenitor cells. No significant differences in cell type enrichment were identified in the TCGA dataset. Predicted immunotherapy response scores were not significantly different between races in both cohorts. Conclusion Our results show differences in genes and pathways associated with inflammation and immune cell recruitment which may impact anti-tumor activity. Our future work will include experimental validation of interesting genes accounting for the differences. Citation Format: Dimitri F. Joseph, Ellen Li, Bin Chen, Joseph F. LaComb, Alexandra Guillaume. Deciphering molecular and cellular differences between black and white colorectal cancers through in-depth transcriptomic analyses [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A010.

Application of metabolic GM (1,1,th,p) power model in fresh e-commerce prediction

Aiming at the prediction problem of fresh e-commerce industry, this paper attempts to combine the metabolic theory with the improved GM (1,1) power model. The article introduces the traditional GM (1,1) power model to enhance the adaptability of the model to the data series, and at the same time, a new parameter is introduced when constructing the background value, the background value is represented as a linear function of adjacent sequence points, and the form and solution method of the two specific models are given, with the goal of minimizing the average relative error, and the power exponential and new parameters are co-optimized by genetic algorithm. The optimal modeling dimension is determined through model testing, and on this basis, the metabolic GM (1,1,th,p) power model is established, and the model is applied to the prediction of the transaction scale of the fresh e-commerce industry. The results show that the improved GM (1,1) power model can significantly improve the fitting accuracy compared with the original model, and the metabolic GM(1,1,th,p) power model has good performance in the prediction problem of fresh e-commerce.

Accurate and lightweight MRI super-resolution via multi-scale bidirectional fusion attention network.

High-resolution magnetic resonance (MR) imaging has attracted much attention due to its contribution to clinical diagnoses and treatment. However, because of the interference of noise and the limitation of imaging equipment, it is expensive to generate a satisfactory image. Super-resolution (SR) is a technique that enhances an imaging system's resolution, which is effective and cost-efficient for MR imaging. In recent years, deep learning-based SR methods have made remarkable progress on natural images but not on medical images. Most existing medical images SR algorithms focus on the spatial information of a single image but ignore the temporal correlation between medical images sequence. We proposed two novel architectures for single medical image and sequential medical images, respectively. The multi-scale back-projection network (MSBPN) is constructed of several different scale back-projection units which consist of iterative up- and down-sampling layers. The multi-scale machine extracts different scale spatial information and strengthens the information fusion for a single image. Based on MSBPN, we proposed an accurate and lightweight Multi-Scale Bidirectional Fusion Attention Network(MSBFAN) that combines temporal information iteratively. That supplementary temporal information is extracted from the adjacent image sequence of the target image. The MSBFAN can effectively learn both the spatio-temporal dependencies and the iterative refinement process with only a lightweight number of parameters. Experimental results demonstrate that our MSBPN and MSBFAN are outperforming current SR methods in terms of reconstruction accuracy and parameter quantity of the model.

A novel self-adaptive fractional grey Euler model with dynamic accumulation order and its application in energy production prediction of China

In the fractional grey model, the new information priority principle has always been pursued by researchers. However, it does not mean that new information is the most important, because in reality, there are always some special moments, and the information they represent will profoundly affect the future development. That is, the most important data may be in the middle of the sequence, not the latest data. Therefore, this paper proposes a periodic variable order accumulated generating operation, which can switch the priority of new and old information with time. In terms of model structure, this paper presents a new variable coefficient whitening equation with self-adaptive structure. That is, a new fractional order grey Euler model with dynamic accumulation order (DOFGM(1,1)) is proposed in this paper. The new model combines the adjacent sequence operator, therefore the newly generated sequence is less random. By adjusting the model parameters, the structure of the model can be changed, so that the model has the features of selecting the adaptive structure. By comparison, the differential evolution algorithm is selected to optimize the hyperparameters of the model. In particular, the robustness of the model is validated by introducing perturbations to the raw data to imitate errors generated during data collection. Finally, three actual cases of China's hydropower generation, China's natural gas production and China's total primary energy production are predicted; the prediction result shows that the new model has higher prediction accuracy than the other six models. The results indicate that the proposed model benefits from its adaptive structure and produces reliable predictions. According to these prediction results, relevant suggestions on the development of China's energy are provided to decision makers.

ODP547 Familial Carney Complex: Follow Up of a Family With Negative PRKAR1A Genetic Screening

Abstract Background Carney's complex (CNC) is a rare genetic multiple neoplasia syndrome, with involvement in several systems, among them, acromegaly is a possible condition, according to the literature, seen in about 10% of cases. PPRKAR1A is the most known gene evolved. The genetic origin of 59% of patients with CNC has not yet been elucidated. ClinicalCases A 17-year-old malewithtall stature, withstigmaofgigantism, GH 9.89 ng/ml and IGF-1 1.5 times higher reference value, MRI with pituitary adenoma of 0.7cm. After resection transfenoidal endoscopic (TSE) thepathology of the tumor revealed a pure GH pituitary adenoma. Echocardiogram showed cardiac myxomas. For that reason, a Carney complex was established. In the search for other alterations present in the syndrome, a nodule was found in the right testicle, which after nodulectomy shown a Leydig Cell Tumor. After these findings, we invited all family members to perform screening to identify possible involvement of the CNC. Two brothers, including a twin, and their mother also had stigma of acromegaly, all with pituitary adenoma and laboratorial diagnostic. The two menunderwentTSE surgery reassuring GH secretion by the tumor. The elderly brother had aggressive microcalcilfications in bilateral testicles. After bilateral orchiectomy was diagnosed witha large cell calcifying sertoli cell tumor. The twin brother also had cardiac mixomas and macrocalcifications in testicle but without signs of malignancy. The mother had athyroid ultrasound showing a multinodular goiter and breast lesions also with no signs of malignancy. She also had a pituitary microadenoma,butrefused the surgery and is currently using thesomatostatinanalog. CNC is a multiple neoplasia syndromeusually characteriszed by lentiginosis, multiple neoplasias and signs of endocrine overactivity, particularly Primary Pigmented Nodular Adrenal Disease (PPNAD) and myxomas. It is a rare condition and its prevalence remains unknown. A patogenic allelic variant (PAV) of PRKAR1A is found in 37% of patients with sporadic CNC and more than 70% of patients with familial CNC. To this date, at least 130 different mutations have been described in more than 400 families around the world, distributed across the ten coding exons (PRKAR1A has 11 exons, but exon 1 is non-coding and rarely mutated) and in the adjacent intronic sequences. In 2014, a germline triplication of the exon of PRKACB gene has been identified in pacient who did not harbour a PRKAR1A mutation. In our case, a search of PAV was realized by exome NGS and CG-Array but we found no evidence of variant that can explain the occurence of CNC. Conclusion We describe the follow-up of a family with CNC without PAV identified so far. Presentation: No date and time listed

Gluing blood into gel by electrostatic interaction using a water-soluble polymer as an embolic agent

Liquid embolic agents are widely used for the endovascular embolization of vascular conditions. However, embolization based on phase transition is limited by the adhesion of the microcatheter to the embolic agent, use of an organic solvent, unintentional catheter retention, and other complications. By mimicking thrombus formation, a water-soluble polymer that rapidly glues blood into a gel without triggering coagulation was developed. The polymer, which consists of cationic and aromatic residues with adjacent sequences, shows electrostatic adhesion with negatively charged blood substances in a physiological environment, while common polycations cannot. Aqueous polymer solutions are injectable through clinical microcatheters and needles. The formed blood gel neither adhered to the catheter nor blocked the port. Postoperative computed tomography imaging showed that the polymer can block the rat femoral artery invivo and remain at the injection site without nontarget embolization. This study provides an alternative for the development of waterborne embolic agents.

Speech Errors in the Production of Initial Consonant Clusters: The Roles of Frequency and Sonority.

One of the central questions in speech production research is to what degree certain structures have an inherent difficulty and to what degree repeated encounter and practice make them easier to process. The goal of this article was to determine the extent to which frequency and sonority distance of consonant clusters predict production difficulties. We used a tongue twister paradigm to elicit speech errors on syllable-initial German consonant clusters and investigated the relative influences of cluster frequency and sonority distance between the consonants of a cluster on production accuracy. Native speakers of German produced pairs of monosyllabic pseudowords beginning with consonant clusters at a high speech rate. Error rates decreased with increasing frequency of the consonant clusters. A high sonority distance, on the other hand, did not facilitate a cluster's production, but speech errors led to optimized sonority structure for a subgroup of clusters. In addition, the combination of consonant clusters in a stimulus pair has a great impact on production accuracy. These results suggest that both frequency of use and sonority distance codetermine production ease, as well as syntagmatic competition between adjacent sound sequences.

Prime editing optimized RTT permits the correction of the c.8713C>T mutation in DMD gene

Duchenne muscular dystrophy is a severe debilitating genetic disease caused by different mutations in the DMD gene leading to the absence of dystrophin protein under the sarcolemma. We used CRISPR-Cas9 prime editing technology for correction of the c.8713C>T mutation in the DMD gene and tested different variations of reverse transcription template (RTT) sequences. We increased by 3.8-fold the editing percentage of the target nucleotide located at+13. A modification of the protospacer adjacent motif sequence (located at+6) and a silent mutation (located at+9) were also simultaneously added to the target sequence modification. We observed significant differences in editing efficiency in interconversion of different nucleotides and the distance between the target, the nicking site, and the additional mutations. We achieved 22% modifications in myoblasts of a DMD patient, which led to dystrophin expression detected by western blot in the myotubes that they formed. RTT optimization permitted us to improve the prime editing of a point mutation located at+13 nucleotides from the nick site to restore dystrophin protein.

Hybrid Vigor: Importance of Hybrid λ Phages in Early Insights in Molecular Biology.

Laboratory-generated hybrids between phage λ and related phages played a seminal role in establishment of the λ model system, which, in turn, served to develop many of the foundational concepts of molecular biology, including gene structure and control. Important λ hybrids with phages 21 and 434 were the earliest of such phages. To understand the biology of these hybrids in full detail, we determined the complete genome sequences of phages 21 and 434. Although both genomes are canonical members of the λ-like phage family, they both carry unsuspected bacterial virulence gene types not previously described in this group of phages. In addition, we determined the sequences of the hybrid phages λ imm21, λ imm434, and λ h434 imm21. These sequences show that the replacements of λ DNA by nonhomologous segments of 21 or 434 DNA occurred through homologous recombination in adjacent sequences that are nearly identical in the parental phages. These five genome sequences correct a number of errors in published sequence fragments of the 21 and 434 genomes, and they point out nine nucleotide differences from Sanger's original λ sequence that are likely present in most extant λ strains in laboratory use today. We discuss the historical importance of these hybrid phages in the development of fundamental tenets of molecular biology and in some of the earliest gene cloning vectors. The 434 and 21 genomes reinforce the conclusion that the genomes of essentially all natural λ-like phages are mosaics of sequence modules from a pool of exchangeable segments.

Tracking of progressing human DNA polymerase δ holoenzymes reveals distributions of DNA lesion bypass activities.

During DNA replication, DNA lesions in lagging strand templates are initially encountered by DNA polymerase δ (pol δ) holoenzymes comprised of pol δ and the PCNA processivity sliding clamp. These encounters are thought to stall replication of an afflicted template before the lesion, activating DNA damage tolerance (DDT) pathways that replicate the lesion and adjacent DNA sequence, allowing pol δ to resume. However, qualitative studies observed that human pol δ can replicate various DNA lesions, albeit with unknown proficiencies, which raises issues regarding the role of DDT in replicating DNA lesions. To address these issues, we re-constituted human lagging strand replication to quantitatively characterize initial encounters of pol δ holoenzymes with DNA lesions. The results indicate pol δ holoenzymes support dNTP incorporation opposite and beyond multiple lesions and the extent of these activities depends on the lesion and pol δ proofreading. Furthermore, after encountering a given DNA lesion, subsequent dissociation of pol δ is distributed around the lesion and a portion does not dissociate. The distributions of these events are dependent on the lesion and pol δ proofreading. Collectively, these results reveal complexity and heterogeneity in the replication of lagging strand DNA lesions, significantly advancing our understanding of human DDT.

Species-specific chromatin landscape determines how transposable elements shape genome evolution.

Transposable elements (TEs) are selfish genetic parasites that increase their copy number at the expense of host fitness. The 'success', or genome-wide abundance, of TEs differs widely between species. Deciphering the causes for this large variety in TE abundance has remained a central question in evolutionary genomics. We previously proposed that species-specific TE abundance could be driven by the inadvertent consequences of host-direct epigenetic silencing of TEs-the spreading of repressive epigenetic marks from silenced TEs into adjacent sequences. Here, we compared this TE-mediated local enrichment of repressive marks, or 'the epigenetic effect of TEs', in six species in the Drosophila melanogaster subgroup to dissect step-by-step the role of such effect in determining genomic TE abundance. We found that TE-mediated local enrichment of repressive marks is prevalent and substantially varies across and even within species. While this TE-mediated effect alters the epigenetic states of adjacent genes, we surprisingly discovered that the transcription of neighboring genes could reciprocally impact this spreading. Importantly, our multi-species analysis provides the power and appropriate phylogenetic resolution to connect species-specific host chromatin regulation, TE-mediated epigenetic effects, the strength of natural selection against TEs, and genomic TE abundance unique to individual species. Our findings point toward the importance of host chromatin landscapes in shaping genome evolution through the epigenetic effects of a selfish genetic parasite.

CRISPR/Cas Genome Editing—Can It Become a Game Changer in Future Fisheries Sector?

Fisheries and aquaculture are the fastest-growing food-producing sector and rapidly becoming an important element for the global food security since they are the primary source of seafood and high animal protein in the human diet. Genome editing offers new possibilities such as the clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein (Cas9) technology, which has the potential to accelerate the sustainable genetic improvement in fisheries and aquaculture. The CRISPR/Cas9 system has four key components, namely, target DNA, Cas9, the protospacer adjacent motif sequence, and the guide RNA or single-guide RNA. CRISPR/Cas is cheaper, easier, and more precise than the other genome editing technologies and can be used as a new breeding technology in fisheries and aquaculture to solve the far-reaching challenges. The attributes like high fecundity, external fertilization, short generation interval, the established method of breeding, and the larval rearing of most aquaculture species have advantages for CRISPR/Cas9 genome editing applications. CRISPR/Cas9 has recently been applied to the traits valued in some aquaculture species (almost >20 species), targeting the main traits of traditional genetic improvement initiatives like growth, disease resistance, reproduction, sterility, and pigmentation. Genome editing can fast forward the breeding process with precision where changes occur in the targeted genes. The probability of desired changes occurring and passing the trait in the next generation is high, so it takes 1-3 generations to establish a breed. Moreover, CRISPR/Cas genome editing rapidly introduces favorable changes by disrupting genes with targeted minor changes, in contrast to transgenesis, which introduces foreign genes into the host genome and thereby alleviates major public concerns on safety. Although the CRISPR/Cas technology has a tremendous potential, there are several technical challenges and regulatory and public issues concerning the applications in fisheries and the aquaculture breeding sector. Nonetheless, the exciting point in the CRISPR/Cas9 genome editing is that two CRISPR-edited fish, namely, red sea bream and tiger puffer developed by the Kyoto-based startup got approval and are now on the market for sale, and another fish, FLT-01 Nile tilapia developed by the AquaBounty, is not classified under genetically modified organism regulatory. However, there is still a way to go before it revolutionizes and becomes viable in commercial aquaculture as the new breeding technology for aquaculture-important traits and species.

A Map of 3' DNA Transduction Variants Mediated by Non-LTR Retroelements on 3202 Human Genomes.

Simple SummaryDuring the transcription of non-LTR retroelements, such as LINEs and SVAs, the transcriptional termination signal at the 3′ end might be ignored by RNA polymerase. As a result, the transcription terminates at another downstream signal, creating a chimeric transcriptional readthrough. Termed 3′ DNA transduction, this process copies the 3′ flanking region along with the retroelement sequence to a new genomic locus, which influences the structure of the genome and occasionally possesses a functional impact. To discover putative non-LTR retroelement-driven 3′ DNA transductions, we analyzed the new dataset (n = 3202) of the 1000 Genomes Project. Our results indicate that 3′ transduction derived by non-LTR retroelements is a relatively common phenomenon in the human genome and that their discovery needs to be more appreciated in genome projects.As one of the major structural constituents, mobile elements comprise more than half of the human genome, among which Alu, L1, and SVA elements are still active and continue to generate new offspring. One of the major characteristics of L1 and SVA elements is their ability to co-mobilize adjacent downstream sequences to new loci in a process called 3′ DNA transduction. Transductions influence the structure and content of the genome in different ways, such as increasing genome variation, exon shuffling, and gene duplication. Moreover, given their mutagenicity capability, 3′ transductions are often involved in tumorigenesis or in the development of some diseases. In this study, we analyzed 3202 genomes sequenced at high coverage by the New York Genome Center to catalog and characterize putative 3′ transduced segments mediated by L1s and SVAs. Here, we present a genome-wide map of inter/intrachromosomal 3′ transduction variants, including their genomic and functional location, length, progenitor location, and allelic frequency across 26 populations. In total, we identified 7103 polymorphic L1s and 3040 polymorphic SVAs. Of these, 268 and 162 variants were annotated as high-confidence L1 and SVA 3′ transductions, respectively, with lengths that ranged from 7 to 997 nucleotides. We found specific loci within chromosomes X, 6, 7, and 6_GL000253v2_alt as master L1s and SVAs that had yielded more transductions, among others. Together, our results demonstrate the dynamic nature of transduction events within the genome and among individuals and their contribution to the structural variations of the human genome.

Characterization of CRISPR-Cas systems in Bifidobacterium breve.

The clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein (Cas) system is an important adaptive immune system for bacteria to resist foreign DNA infection, which has been widely used in genotyping and gene editing. To provide a theoretical basis for the application of the CRISPR-Cas system in Bifidobacterium breve , the occurrence and diversity of CRISPR-Cas systems were analysed in 150 B. breve strains. Specifically, 47 % (71/150) of B. breve genomes possessed the CRISPR-Cas system, and type I-C CRISPR-Cas system was the most widely distributed among those strains. The spacer sequences present in B. breve can be used as a genotyping marker. Additionally, the phage assembly-related proteins were important targets of the type I-C CRISPR-Cas system in B. breve , and the protospacer adjacent motif sequences were further characterized in B. breve type I-C system as 5′-TTC-3′. All these results might provide a molecular basis for the development of endogenous genome editing tools in B. breve .

Genome-wide screening for genes involved in the epigenetic basis of fragile X syndrome.

SummaryFragile X syndrome (FXS), the most prevalent heritable form of intellectual disability, is caused by the transcriptional silencing of the FMR1 gene. The epigenetic factors responsible for FMR1 inactivation are largely unknown. Here, we initially demonstrated the feasibility of FMR1 reactivation by targeting a single epigenetic factor, DNMT1. Next, we established a model system for FMR1 silencing using a construct containing the FXS-related mutation upstream to a reporter gene. This construct was methylated in vitro and introduced into a genome-wide loss-of-function (LOF) library established in haploid human pluripotent stem cells (PSCs), allowing the identification of genes whose functional loss reversed the methylation-induced silencing of the FMR1 reporter. Selected candidate genes were further analyzed in haploid- and FXS-patient-derived PSCs, highlighting the epigenetic and metabolic pathways involved in FMR1 regulation. Our work sheds light on the mechanisms responsible for CGG-expansion-mediated FMR1 inactivation and offers novel targets for therapeutic FMR1 reactivation.