Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “integration”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,477 records · Page 82Linked to original sources

Integration of single cell multiomics data by deep transfer hypergraph neural network.

Multi-omics characterization of individual cells offers remarkable potential for analyzing the dynamics and relationships of gene regulatory states across millions of cells. How to integrate multimodal data is an open problem, existing integration methods struggle with accuracy and modality-specific biological variation retention. In this paper, we present scHyper (scalable, interpretable machine learning for single cell integration), a low-code and data-efficient deep transfer model designed for integrating paired and unpaired single-cell multimodal data. We benchmark scHyper against datasets from different multimodal data. ScHyper learns a low-dimensional representation and aligns the covariance matrices of the measured modalities, achieving high accuracy even with large scale atlas-level datasets with low memory and computational time across different cell lines, shedding light on regulatory relationships between different types of omics. Altogether, we show that scHyper is a versatile and robust tool for cell-type label transfer and integration from multimodal single-cell datasets.

Single-Cell Analysis↗

iMap: a database-driven utility to integrate and access the genetic and physical maps of maize.

MOTIVATION: Because of the unique biological features, a bioinformatic platform for the integrated genetic and physical map of maize is required for storing, integrating, accessing and visualizing the underlying data. RESULTS: The goal of the Maize Mapping Project is to develop a fully integrated genetic and physical map for maize. To display this integrated map, we have developed iMap. iMap has three main components: a relational database (iMapDB), a map graphic browser (iMap Viewer) and a search utility (iMap Search). iMapDB is populated with current genetic and physical map data, describing relationships among genetic loci, molecular markers and bacterial artificial chromosome (BAC) contigs. The database also contains integrated information produced by applying a set of anchoring rules to assign BAC contigs to specific locations on the genetic map. The iMap Viewer and iMap Search functions are combined in the user interface to allow viewing and retrieving many types of genetic and physical map data. The iMap Viewer features side-by-side chromosome-based displays of the genetic map and associated BAC contigs. For each genetic locus, information about marker type or contig can be viewed via pop-up windows that feature links to external data resources. Searches can be conducted for genetic locus, probe or sequence accession number; search results include relevant map positions, anchored BAC contigs and links to the graphical display of relevant chromosomes. iMap can be accessed at http://www.maizemap.org AVAILABILITY: The iMap utility package is available for non-commercial use upon request from the authors.

Chromosome Mapping↗

Viral protein R regulates nuclear import of the HIV-1 pre-integration complex.

Replication of human immunodeficiency virus type 1 (HIV-1) in non-dividing cells critically depends on import of the viral pre-integration complex into the nucleus. Genetic evidence suggests that viral protein R (Vpr) and matrix antigen (MA) are directly involved in the import process. An in vitro assay that reconstitutes nuclear import of HIV-1 pre-integration complexes in digitonin-permeabilized cells was used to demonstrate that Vpr is the key regulator of the viral nuclear import process. Mutant HIV-1 pre-integration complexes that lack Vpr failed to be imported in vitro, whereas mutants that lack a functional MA nuclear localization sequence (NLS) were only partially defective. Strikingly, the import defect of the Vpr- mutant was rescued when recombinant Vpr was re-added. In addition, import of Vpr- virus was rescued by adding the cytosol of HeLa cells, where HIV-1 replication had been shown to be Vpr-independent. In a solution binding assay, Vpr associated with karyopherin alpha, a cellular receptor for NLSs. This association increased the affinity of karyopherin alpha for basic-type NLSs, including that of MA, thus explaining the positive effect of Vpr on nuclear import of the HIV-1 pre-integration complex and BSA-NLS conjugates. These results identify the biochemical mechanism of Vpr function in transport of the viral pre-integration complex to, and across, the nuclear membrane.

Biological Transport↗

Building integrated health systems in central and eastern Europe: an analysis of WHO and World Bank views and their relevance to health systems in transition.

BACKGROUND: Two questions are addressed. i) What are the views on health and health systems as expressed in the World Development Report 2000/2001 of the WB and the World Health Report 2000 and Health 21 of the World Health Organization, and how compatible are those views? ii) To what extent will compliance of CEEC and NIS with the WHO and WB recommendations result in health systems that produce maximum health for all by adequately addressing the needs of their populations? METHOD: The reports prepared by the World Bank and the World Health Organization were assessed against the theoretical framework of a needs-based public health approach. RESULTS: It is observed that the WHO and WB approaches are currently converging, although there remain differences in their respective focuses. The main merit of the WHO approach is its focus on performance and the systems approach towards health (care). The merit of the WB view is the integrated approach to health, education and poverty. It is argued that CEEC and NIS need to anticipate an ageing population and growing numbers of chronically ill. This calls for integrated health care systems and more integrated funding and payment systems. CONCLUSION: The recommendations provided in the WHR and the WDR with regard to integrated care and integrated financing remain rather abstract. Advisors of CEEC and NIS on health care reform and Western assistance projects should focus more on future needs, in order to avoid building health systems that consistently lag behind the needs of their populations.

Delivery of Health Care, Integrated↗

Simplifying multiplex genome engineering in Saccharomyces cerevisiae with intron-mediated Random Assembly and INtegration (RAIN).

Engineering of multistep enzymatic pathways often involves extensive optimization of heterologous gene expression levels and requires cloning of promoter and open reading frames (ORFs) to generate expression cassettes. We present work on a nascent method for multiplex genome engineering in Saccharomyces cerevisiae that negates the requirement for cloning of expression cassettes. Our system, Random Assembly and INtegration (RAIN), uses intron-mediated homologous recombination (HR) for random in vivo assembly of exogenous promoter and ORF libraries, which are combined and cotransformed in a one-pot method. The libraries include consensus homology arms which target long terminal repeat regions of the Ty1 retrotransposon, providing over a hundred possible integration loci. In this way, our developmental system aims to negate the need for in vitro combinatorial cloning of promoters and ORFs to generate expression cassettes, simplifying in vitro DNA preparation before multiplex genome engineering. This paper presents findings from a series of experiments to demonstrate a proof of concept for the RAIN system. These include: the first reported use of intron-mediated assembly of promoters and ORFs for expression of a functional gene product; up to three markerless genomic integrations; and up to five integrations with antibiotic selection. We also present a number of innovations to improve integration efficiency during multiplex engineering in S. cerevisiae including: SGS1 gene knockout; disruption of heteroduplex rejection; modified Cas9 expression architecture; and overexpression of HR genes RAD52, MRE11, and RAD59. To demonstrate how our system can be used for single transformation phenotype engineering of multiple strains, we also transformed a library of methylotrophy associated genes to generate four new strains that were able to grow on a solid minimal medium with methanol as the sole additional carbon source. Our findings contribute to the ongoing efforts to improve multiplex genome engineering tools in S. cerevisiae, and provide the foundations for further development of a novel toolbox for generating useful genetic diversity for metabolic pathway engineering.

Saccharomyces cerevisiae↗

A multimegabase cluster of snRNA and tRNA genes on chromosome 1p36 harbours an adenovirus/SV40 hybrid virus integration site.

Adenovirus type 12 (Ad12) induces gaps at chromosomal bands 1p36, 1q21, 1q42-43 and 17q21 after infection of human embryonic kidney cells. Three of these bands harbour small nuclear RNA genes or pseudogenes, but the study of a possible relationship has been hampered by the lytic character of adenovirus infection. A non-lytic Ad5/SV40 hybrid virus preferentially integrates at 1p36 and the integration site has been cloned. Chromosomal band 1p36 encodes genes for small nuclear RNA U1 (RNU-1) and for the tRNAs of glutamic acid (TRE) and asparagine (TRN). Each of these genes is encoded by 15-30 copies. We studied the organization of these genes and of the viral integration site by pulsed field gel electrophoresis (PFGE) and analysis of yeast artificial chromosomes (YACs). We show that RNU-1, TRE and TRN genes are scattered over a region of probably more than 2 Mb with intergenic distances of up to 125 kb. The Ad5/SV40 integration site maps to identical chromosomal NotI fragments as RNU-1 and TRE. Fine mapping of a YAC shows that the integration site is within 40-70 kb of genes for RNU-1, TRN and TRE.

Adenoviruses, Human↗

MoMuLV proviral integrations identified by Sup-F selection in tumors from infected myc/pim bitransgenic mice correlate with activation of the gfi-1 gene.

Infecting mice with a mutant Moloney murine leukemia virus which contains the bacterial suppressor tRNA supF in its LTR allows rapid cloning of proviral integration sites from genomic tumour DNA. In a previous study Emu pim-1/Emu L-myc bitransgenic mice had been inoculated neonatally with MoMuLV supF virus. The retroviral infection led to acceleration of lymphomagenesis indicating the proviral activation of further oncogenes cooperating with myc and pim-1 in tumour development. Using a functional supF screen for analysis of genomic mouse tumour DNA libraries which had been constructed in the phage vector EMBL3A, a common proviral integration site on mouse chromosome 5 was cloned and found to be identical to the proviral integration site evi-5 which has recently been identified in an AKXD T-cell lymphoma and which is located 18 kb upstream of the gfi-1 gene. Tumours bearing evi-5 integrations showed an enhanced gfi-1 expression level suggesting that gfi-1 is the target gene for insertions at the evi-5 locus. Together with three other previously described Moloney integration clusters all responsible for enhanced gfi-1 expression the number of tumours from infected double transgenic Emu L-myc/Emu pim-1 transgenic mice with retrovirally activated gfi-1 added up to 53% underscoring the role of GFI-1 as an effective collaborator for MYC and PIM-1 in the process of lymphomagenesis.

Animals↗

ArrayXPath II: mapping and visualizing microarray gene-expression data with biomedical ontologies and integrated biological pathway resources using Scalable Vector Graphics.

SUMMARY: ArrayXPath (http://www.snubi.org/software/ArrayXPath/) is a web-based service for mapping and visualizing microarray gene-expression data with integrated biological pathway resources using Scalable Vector Graphics (SVG). Deciphering the crosstalk among pathways and integrating biomedical ontologies and knowledge bases may help biological interpretation of microarray data. ArrayXPath is empowered by integrating gene-pathway, disease-pathway, drug-pathway and pathway-pathway correlations with integrated Gene Ontology, Medical Subject Headings and OMIM Morbid Map-based annotations. We applied Fisher's exact test and relative risk to evaluate the statistical significance of the correlations. ArrayXPath produces Javascript-enabled SVGs for web-enabled interactive visualization of gene-expression profiles integrated with gene-pathway-disease interactions enriched by biomedical ontologies.

Cluster Analysis↗

Review of integrated mental health and substance abuse treatment for patients with dual disorders.

Patients with severe mental disorders such as schizophrenia and co-occurring substance use disorders traditionally received treatments for their two disorders from two different sets of clinicians in parallel treatment systems. Dissatisfaction with this clinical tradition led to the development of integrated treatment models in which the same clinicians or teams of clinicians provide substance abuse treatment and mental health treatment in a coordinated fashion. We reviewed 36 research studies on the effectiveness of integrated treatment for dually diagnosed patients. Studies of adding dual-disorders groups to traditional services, studies of intensive integrated treatments in controlled settings, and studies of demonstration projects have thus far yielded disappointing results. On the other hand, 10 recent studies of comprehensive, integrated outpatient treatment programs provide encouraging evidence of the programs' potential to engage dually diagnosed patients in services and to help them reduce substance abuse and attain remission. Outcomes related to hospital use, psychiatric symptoms, and other domains are less consistent. Several program features appear to be associated with effectiveness: assertive outreach, case management, and a longitudinal, stage-wise, motivational approach to substance abuse treatment. Given the magnitude and severity of the problem of dual disorders, more controlled research on integrated treatment is needed.

Case Management↗

Characteristics of residential community integration programs for adults with brain injury.

OBJECTIVES: To gather data on some quantifiable characteristics of residential community integration programs available to adults with brain injury. PARTICIPANTS: Directors, assistant directors, or coordinators of community integration programs for people with brain injury. MEASUREMENT TOOLS: The Community Integration Program Questionnaire (CIPQ). DESIGN: Nationwide telephone survey of 30 residential community integration programs between June 2002 and June 2003. RESULTS: There was tremendous variability in the areas of staffing, client, and programmatic characteristics. Staff-to-client ratio varied from 0.77 to 3.3. Lengths of stay ranged from 0.13 to 288 months. Times from injury to admission varied from 0.2 to 180 months. CONCLUSIONS: The considerable variability in characteristics of residential community integration programs for adults with brain injury presents significant challenges to researchers seeking to identify vital program components and to consumers attempting to compare programs.

Adult↗

Mixing it up: integrating evidence-based medicine and patient care.

OBJECTIVE: To teach internal medicine residents to use evidence-based medicine (EBM) in their interactions with patients by creating curricula that integrate EBM into clinical topics in internal medicine. DESCRIPTION: The last several years have brought the wide-spread inclusion of EBM in internal medicine training programs in the United States. However, EBM is often taught as an independent topic and is poorly integrated into the clinical teaching of trainees. Most EBM education occurs in a journal-club format, focusing on question development, searching, and critical appraisal. The challenge of discussing the evidence with patients is rarely addressed. We set out to integrate EBM teaching into new curricula in women's health, addiction medicine, and topics in anticoagulation. During the first of two ambulatory blocks of the year, residents participate in an EBM seminar series in which they present cases, generate questions, and critically appraise the evidence. Second-year residents present articles on therapy or diagnosis and third-year residents present articles on diagnosis, meta-analysis, or decision and economic analysis. Both the women's health curriculum and the anticoagulation curriculum are presented during the second ambulatory block of the year as four half-day small-group seminars. The women's health curriculum is presented to the second-year residents and the anticoagulation curriculum is presented to the third-year residents. Both curricula are case-based and emphasize essential skills in patient care, including interview techniques, sensitivity to psychosocial issues, and skills in evidence-based patient care. Teaching EBM is not identified to the residents as a goal of these curricula; instead EBM, psychosocial medicine, and communication skills are woven into the content material and taught in the context of the broader subject matter. Learners are expected to integrate these concepts into actual practice. The curricula utilize clinical vignettes and role-plays to link EBM concepts such as number needed to treat or decision analysis to real-patient decisions. Residents are also asked to apply the evidence in their own patient encounters for further discussion at later sessions. Simpler concepts of therapy and diagnosis are covered during the second year in women's health and the more complex concepts of meta-analysis; decision analysis, and economic analysis are covered during the third year in anti-coagulation. DISCUSSION: The women's health curriculum was introduced in the spring of 2000; the anticoagulation curriculum was introduced in the spring of 2001. Both have been well received and seem to have impacted the ability of our housestaff to incorporate EBM into patient care. Currently under development in this series is a curriculum in addiction medicine for interns that will use a similar approach to provide an overview of EBM topics and their integration into the flow of patient care. We feel that these educational programs have helped EBM to bridge the gap between the classroom and the exam room.

Delivery of Health Care, Integrated↗

The effects of managed care on physician and clinical integration in hospitals.

OBJECTIVE: To empirically estimate the effects that managed care has had on physician and clinical integration in urban hospitals. DATA SOURCES: The 1993 Hospital-Physician Relationship Survey conducted for the Prospective Payment Assessment Commission, augmented with data from a variety of secondary sources. The entire 1,495 responding hospitals were used to construct measures of integration; 591 responding hospitals in urban areas were used for the managed care analysis. STUDY DESIGN: Factor analysis was used to reduce 23 integration variables into 5 physician and 3 clinical integration factors. Two-stage least-squares regression techniques were used to estimate the effects of endogenous managed care. Models were estimated for all urban hospitals and for hospital subsets based upon ownership, multi-hospital system status, and teaching. PRINCIPAL FINDINGS: Other things equal, physician involvement in hospital management and governance increased with managed care involvement; to a lesser degree, the use of physician organization arrangements and other joint ventures also increased. Practice management and support services were lower in hospitals with high managed care activity. Larger hospitals, investor owned, system, and non-teaching hospitals had larger managed care revenues. Managed care revenues were lower in more concentrated hospital markets. CONCLUSIONS: The relationship between managed care and physician and clinical integration is relatively modest. Much of the realignment under managed care has been limited to certain types of efforts. Those efforts can best be described as foundation-building rather than comprehensive or fundamental.

Data Collection↗

Family perspectives on integrated child health information systems.

The perspectives of families, and especially parents of children with special health care needs, need to be better understood by the government agencies, health care providers, associations, and information systems vendors that are integrating child health information systems. To date, research on children with special health care needs has not included the perspectives of parents on integrated child health information systems. Interviews were conducted with a limited number of parents of children with special health care needs and a young adult with special health care needs about their perspectives on integrated health information systems needs. The interviews revealed common themes: (1) parents have experienced the benefits of information technology for health care purposes, (2) parents believe integrated health information systems could help to coordinate their children's health care, (3) parents believe information technology can help improve accuracy and timeliness of information, (4) parents of children with special health care needs believe their children's health information should be available to those who need it, but safeguards must be in place, (5) parents believe health information systems can improve health care, but it is not the highest priority health care issue for them, and (6) parents believe that their involvement in issues related to children with special health care needs, including information technology, is critical. Parents of children with special health care needs hold strong opinions about their children's health care, including health information systems. Parents need to be central to discussions about development of integrated child health information systems if we are to develop information systems that serve the needs of children with special health care needs and their families.

Adolescent↗

Key elements for successful integrated health information systems: lessons from the States.

The Genetic Services Branch, Maternal and Child Health Bureau of the Health Services and Resources Administration has provided funding to state health departments to integrate their newborn dried blood-spot screening programs with other early child health information systems since 1999. In 2001, All Kids Count conducted site visits to these grantees to identify and describe best practices in planning, developing, and implementing their integration projects. The site visits were organized around 9 key elements considered critical to the success of an information systems integration project: leadership, project governance, project management, stakeholder involvement, organizational and technical strategy, technical support and coordination, financial support and management, policy support and evaluation. Best practices for each of the key elements and 5 lessons learned were documented in Integration of Newborn Screening and Genetic Service Systems with Other Maternal & Child Health Systems: A Sourcebook for Planning and Development. The lessons learned are overarching conclusions that agencies should consider when planning and implementing integrated information systems. This article briefly describes the key elements, their best practices as implemented by states, and the lessons learned.

Child↗

Utilization and cost impact of integrating substance abuse treatment and primary care.

OBJECTIVE: To examine the impact of integrating medical and substance abuse treatment on health care utilization and cost. RESEARCH DESIGN: Randomized clinical trial assigning patients to one of two treatment modalities: an Integrated Care model where primary health care is provided along with substance abuse treatment within the unit and an Independent Care model where medical care is provided in the HMO's primary care clinics independently from substance abuse treatment. SUBJECTS: Adult patients entering treatment at the outpatient Chemical Dependency Recovery Program in Kaiser Sacramento. MEASURES: Medical utilization and cost for 12 months pretreatment and 12 months after treatment entry. RESULTS: For the full, randomized cohort, there were no statistically significant differences between the two treatment groups over time. However, among the subset of patients with substance abuse related medical conditions (SAMC), Integrated Care patients had significant decreases in hospitalization rates (P = 0.04), inpatient days (P = 0.05) and ER use (P = 0.02). Total medical costs per member-month declined from 431.12 US dollars to 200.03 US dollars (P = 0.02). Among SAMC Independent Care patients, there was a downward trend in inpatient days (P = 0.08) and ER costs (P = 0.05) but no statistically significant decrease in total medical cost. CONCLUSIONS: (Non)findings for the full sample suggest that integrating substance abuse treatment with primary care, may not be necessary or appropriate for all patients. However, it may be beneficial to refer patients with substance abuse related medical conditions to a provider also trained in addiction medicine. There appear to be large cost impacts of providing integrated care for such patients.

Adult↗

Comparison between in situ hybridization and real-time PCR technique as a means of detecting the integrated form of human papillomavirus 16 in cervical neoplasia.

Integration of the human papillomavirus (HPV) genome is thought to be one of the causes of cancer progression. However, there is controversy concerning the physical status of HPV 16 in premalignant cervical lesions, and there have been no reports on the concordance between detection of the integrated form of HPV16 by real-time PCR and by in situ hybridization. We investigated specimens of cervical intraepithelial neoplasia (CIN) and invasive carcinomas for the physical status of HPV 16 by real-time PCR and in situ hybridization. The presence of the integrated form was detected by both real-time PCR and in situ hybridization in zero of four cases of CIN1, three of six cases of CIN2, nine of 27 cases of CIN3, and two of six cases of invasive carcinomas. Integrated HPV 16 was present in some premalignant lesions but was not always present in carcinomas. The concordance rate between the two methods for the detection of the presence of the integrated form was 37 of 43 (86%) cases. Real-time PCR and in situ hybridization were found to be complementary and convenient techniques for determining the physical status of the HPV genome. We conclude that a combination of both methods is a more reliable means of assessing the physical status of the HPV genome in cervical neoplasia.

Carcinoma↗

Distinct patterns of alteration of myc genes associated with integration of human papillomavirus type 16 or type 45 DNA in two genital tumours.

We previously described two genital carcinomas (IC2, IC4) containing human papillomavirus type 16 (HPV-16)- or HPV-18-related sequences integrated in chromosomal bands containing the c-myc (8q24) or N-myc (2p24) gene, respectively. The c-myc gene was rearranged and amplified in IC2 cells without evidence of overexpression. The N-myc gene was amplified and highly transcribed in IC4 cells. Here, the sequence of an 8039 bp IC4 DNA fragment containing the integrated viral sequences and the cellular junctions is reported. A 3948 bp segment of the genome of HPV-45 encompassing the upstream regulatory region and the E6 and E7 ORFs was integrated into the untranslated part of N-myc exon 3, upstream of the N-myc polyadenylation signal. Both N-myc and HPV-45 sequences were amplified 10- to 20-fold. The 3' ends of the major N-myc transcript were mapped upstream of the 5' junction. A minor N-myc/HPV-45 fusion transcript was also identified, as well as two abundant transcripts from the HPV-45 E6-E7 region. Large amounts of N-myc protein were detected in IC4 cells. A major alteration of c-myc sequences in IC2 cells involved the insertion of a non-coding sequence into the second intron and their co-amplification with the third exon, without any evidence for the integration of HPV-16 sequences within or close to the gene. Different patterns of myc gene alterations may thus be associated with integration of HPV DNA in genital tumours, including the activation of the protooncogene via a mechanism of insertional mutagenesis and/or gene amplification.

Amino Acid Sequence↗

Using XML technology for the ontology-based semantic integration of life science databases.

Several hundred internet accessible life science databases with constantly growing contents and varying areas of specialization are publicly available via the internet. Database integration, consequently, is a fundamental prerequisite to be able to answer complex biological questions. Due to the presence of syntactic, schematic, and semantic heterogeneities, large scale database integration at present takes considerable efforts. As there is a growing apprehension of extensible markup language (XML) as a means for data exchange in the life sciences, this article focuses on the impact of XML technology on database integration in this area. In detail, a general architecture for ontology-driven data integration based on XML technology is introduced, which overcomes some of the traditional problems in this area. As a proof of concept, a prototypical implementation of this architecture based on a native XML database and an expert system shell is described for the realization of a real world integration scenario.

Algorithms↗