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At least 253 records · Page 14Linked to original sources
PubMed2006

OrthologID: automation of genome-scale ortholog identification within a parsimony framework.

MOTIVATION: The determination of gene orthology is a prerequisite for mining and utilizing the rapidly increasing amount of sequence data for genome-scale phylogenetics and comparative genomic studies. Until now, most researchers use pairwise distance comparisons algorithms, such as BLAST, COG, RBH, RSD and INPARANOID, to determine gene orthology. In contrast, orthology determination within a character-based phylogenetic framework has not been utilized on a genomic scale owing to the lack of efficiency and automation. RESULTS: We have developed OrthologID, a Web application that automates the labor-intensive procedures of gene orthology determination within a character-based phylogenetic framework, thus making character-based orthology determination on a genomic scale possible. In addition to generating gene family trees and determining orthologous gene sets for complete genomes, OrthologID can also identify diagnostic characters that define each orthologous gene set, as well as diagnostic characters that are responsible for classifying query sequences from other genomes into specific orthology groups. The OrthologID database currently includes several complete plant genomes, including Arabidopsis thaliana, Oryza sativa, Populus trichocarpa, as well as a unicellular outgroup, Chlamydomonas reinhardtii. To improve the general utility of OrthologID beyond plant species, we plan to expand our sequence database to include the fully sequenced genomes of prokaryotes and other non-plant eukaryotes. AVAILABILITY: http://nypg.bio.nyu.edu/orthologid/

Algorithms↗
PubMed2025

Isolated lateralized overgrowth and the need for tumor screening: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG).

PURPOSE: To provide diagnostic guidance for individuals with lateralized overgrowth (LO) and implement appropriate screening protocols. LO without a syndromic presentation is considered idiopathic isolated lateralized overgrowth (ILO). METHODS: We performed a literature search of LO syndromes and malignancy risk and reviewed existing guidelines and expert input. RESULTS: We integrated 940 unique articles to form recommendations. We defined LO as significantly larger length and/or girth of aspect(s) of one side of the body compared with its contralateral side. It can be associated with somatic overgrowth syndromes. ILO was previously defined based on clinical features and deemed idiopathic by absence of molecular findings. Much of the tumor risk is likely because of specific LO syndromic causes now identified through improved diagnostic technologies; therefore, the tumor risk in idiopathic ILO is likely lower than previously accepted. CONCLUSION: Mosaicism complicates molecular diagnosis for children with LO. However, conditions such as Beckwith-Wiedemann spectrum and PTEN-related hamartoma tumor syndrome necessitate routine tumor screening. Establishing a specific diagnosis via comprehensive molecular testing on affected tissue will guide screening and management. In cases of idiopathic ILO, location of the overgrowth, estimation of tumor risk, regional practice approaches and family concerns all play roles in determining tumor screening.

Child↗
PubMed2006

The peripheral blood transcriptome dynamically reflects system wide biology: a potential diagnostic tool.

In our genome-wide survey of gene expression in human peripheral blood cells using both an expressed sequence tag (EST) and a microarray hybridization approach, we identified the expression of a large proportion (approximately 80%) of the genes encoded in the human genome. Comparison of the peripheral blood transcriptome with genes expressed in nine different human tissue types revealed that expression of over 80% was shared with any given tissue. We also sought to determine whether those gene transcripts undetected by these methods were also expressed in peripheral blood cells. Using reverse-transcriptase-polymerase chain reaction, we detected additional tissue-specific gene transcripts including beta-myosin heavy chain (heart specific) and insulin (specific to pancreatic islet beta cells), in circulating blood cells. Arguably, the detection of low levels of tissue-specific transcripts could be considered products of "illegitimate" transcription; however, our study also demonstrates that environmental conditions affect the transcriptional regulation of insulin in the peripheral blood. We thus hypothesize that blood cells can act as sentinels of disease and that we could capitalize on this property of blood for the diagnosis/prognosis of disease (the "Sentinel Principle"). Peripheral blood is an ideal surrogate tissue as it is readily obtainable, provides a large biosensor pool in the form of gene transcripts, and response to changes in the macro- and micro-environments is detectable as alterations in the levels of these gene transcripts.

Blood↗
PubMed2024

Critically unwell infants and children with mitochondrial disorders diagnosed by ultrarapid genomic sequencing.

PURPOSE: To characterize the diagnostic and clinical outcomes of a cohort of critically ill infants and children with suspected mitochondrial disorders (MD) undergoing ultrarapid genomic testing as part of a national program. METHODS: Ultrarapid genomic sequencing was performed in 454 families (genome sequencing: n = 290, exome sequencing +/- mitochondrial DNA sequencing: n = 164). In 91 individuals, MD was considered, prompting analysis using an MD virtual gene panel. These individuals were reviewed retrospectively and scored according to modified Nijmegen Mitochondrial Disease Criteria. RESULTS: A diagnosis was achieved in 47% (43/91) of individuals, 40% (17/43) of whom had an MD. Seven additional individuals in whom an MD was not suspected were diagnosed with an MD after broader analysis. Gene-agnostic analysis led to the discovery of 2 novel disease genes, with pathogenicity validated through targeted functional studies (CRLS1 and MRPL39). Functional studies enabled diagnosis in another 4 individuals. Of the 24 individuals ultimately diagnosed with an MD, 79% had a change in management, which included 53% whose care was redirected to palliation. CONCLUSION: Ultrarapid genetic diagnosis of MD in acutely unwell infants and children is critical for guiding decisions about the need for additional investigations and clinical management.

Humans↗
PubMed2001

[Secretion and dynamics of herpes simplex virus in tear and saliva of patients with Bell's palsy].

Herpes simplex virus (HSV) involvement has been clarified as the cause of Bell's palsy by molecular biological techniques. To clarify the direct relationship between virus reactivation and paralysis development, both detection of the virus genome by DNA-diagnostic and quantitative analysis of its time-course change are needed. Using polimerase chain reaction (PCR) method and microplate-hybridization combined, we detected the virus genome in small amount of specimens from patients with Bell's palsy, quantified its number of copies, and examined time-course changes. We attempted to type of HSV in positive specimens. Subjects were 16 patients with Bell's palsy positive for serum anti-HSV IgG antibody (enzyme immunoassay) who visited the outpatient clinic of Department of Otorhinolaryngology, Itabashi Hospital, Nihon University School of Medicine, within 14 days after onset without having any treatment. Tears and saliva from the parotid gland and the submaxillary gland were separately collected from the affected side and healthy side twice or more. A total of 244 specimens was subjected to DNA extraction, PCR, and microplate-hybridization, and HSV DNA was detected in 38 specimens (11.8%) from 5 patients (31%). From sampling time, the highest detection (28.5%) was obtained within 2 weeks after onset. Detection at 3 weeks and later (2.8%) was significantly lower (p < 0.05). DNA was also found on the healthy side, but in comparison between sides, detection on the healthy side (18.9%) was significantly lower than that on the affected side (83.8%) (p < 0.01). In quantitative determination of the virus genome, the amount (number of copies) was large on the affected side and largest early after onset regardless of the clinical course. Positive specimens underwent HSV-typing, and HSV-1 was found in all of them, suggesting that HSV-1 reactivation is a cause of Bell's palsy.

Adolescent↗
PubMed2002

Genome scale comparison of Mycobacterium avium subsp. paratuberculosis with Mycobacterium avium subsp. avium reveals potential diagnostic sequences.

The genetic similarity between Mycobacterium avium subsp. paratuberculosis and other mycobacterial species has confounded the development of M. avium subsp. paratuberculosis-specific diagnostic reagents. Random shotgun sequencing of the M. avium subsp. paratuberculosis genome in our laboratories has shown >98% sequence identity with Mycobacterium avium subsp. avium in some regions. However, an in silico comparison of the largest annotated M. avium subsp. paratuberculosis contigs, totaling 2,658,271 bp, with the unfinished M. avium subsp. avium genome has revealed 27 predicted M. avium subsp. paratuberculosis coding sequences that do not align with M. avium subsp. avium sequences. BLASTP analysis of the 27 predicted coding sequences (genes) shows that 24 do not match sequences in public sequence databases, such as GenBank. These novel sequences were examined by PCR amplification with genomic DNA from eight mycobacterial species and ten independent isolates of M. avium subsp. paratuberculosis. From these analyses, 21 genes were found to be present in all M. avium subsp. paratuberculosis isolates and absent from all other mycobacterial species tested. One region of the M. avium subsp. paratuberculosis genome contains a cluster of eight genes, arranged in tandem, that is absent in other mycobacterial species. This region spans 4.4 kb and is separated from other predicted coding regions by 1,408 bp upstream and 1,092 bp downstream. The gene upstream of this eight-gene cluster has strong similarity to mycobacteriophage integrase sequences. The GC content of this 4.4-kb region is 66%, which is similar to the rest of the genome, indicating that this region was not horizontally acquired recently. Southern hybridization analysis confirmed that this gene cluster is present only in M. avium subsp. paratuberculosis. Collectively, these studies suggest that a genomics approach will help in identifying novel M. avium subsp. paratuberculosis genes as candidate diagnostic sequences.

Animals↗
PubMed2026

RESCUE: An end-to-end multi-agent LLM system for proactive rare-disease patient screening in the EHR.

BACKGROUND: Rare diseases affect a significant portion of the global population, yet patients often endure a lengthy diagnostic odyssey, frequently missing the opportunity for timely diagnoses with exome or genome sequencing (ES/GS). Existing informatics tools often rely on pre-identified patients or rigid, institution-specific rule sets, failing to address the broader operational question of clinical utility and feasibility. METHODS: We introduce RESCUE (Rare Disease Detection and Escalation Support via a Learning Health System), an end-to-end, multi-agent LLM-powered workflow designed for proactive rare-disease diagnosis across the entire electronic health record (EHR). RESCUE utilizes a team of specialized agents including Ontology, Modeling, Screening, and Review, to automate the screening process to identify candidates for diagnostic testing based on their clinical features. The Ontology Agent classifies clinical data into a four-tier genetic-evidence taxonomy; the Modeling Agent builds a positive-unlabeled (PU) XGBoost classifier to identify potential cases; the Screening Agent applies these models across the EHR population; and the Review Agent evaluates candidates by sampling clinical notes to ensure medical necessity and operational feasibility for genomic testing. RESULTS: Using electronic medical record data from a pediatric hospital, our retrospective evaluation on a holdout set (n=12,591) demonstrates strong discrimination between patients who received diagnostic genomic testing and those who did not (AUC 0.808). Of nearly 500,000 patients in the institutional base, 175,842 met inclusion criteria for screening; among these, RESCUE-flagged candidates were 7.4-fold more likely to receive subsequent genomic assessments compared to controls. Blinded manual chart reviews confirmed that RESCUE identifies previously missed, medically appropriate patients for ES/GS with 80% precision, while simultaneously accounting for prior testing history. CONCLUSIONS: By decoupling expert roles into modular agents, RESCUE offers a flexible, scalable, and adaptable framework for screening patients for rare-disease diagnostic genomic testing. This approach overcomes the limitations of traditional rule-based methods and provides a reproducible, agentic pathway to reduce diagnostic delays and improve patient care at an institutional scale.

Journal Article↗
PubMed2026

Molecular DNA enrichment methods for parasite genomic sequencing in clinical samples: a systematic review.

Parasitic diseases such as malaria, Chagas disease, leishmaniases, and helminthiases are major causes of sickness and death in low- and middle-income countries. The high genetic diversity of these pathogens affects virulence, immune evasion, and diagnostic accuracy. Although Whole Genome Sequencing (WGS) is a powerful tool for tracking genetic variants and drug resistance, low parasitemia and the predominance of host DNA limit its application to clinical samples. This study systematically reviewed molecular strategies to improve the recovery of parasite DNA from clinical samples, following PRISMA 2020 guidelines and registered in PROSPERO. Searches of PubMed, Scopus, Web of Science, and LILACS up to December 2025 identified 20 eligible studies, most of which focused on protozoa, particularly Plasmodium spp. The main approaches included hybridization capture, selective whole-genome amplification, host DNA depletion, and in silico enrichment via adaptive sampling. Overall, no single method is suitable for all parasites analyzed; the optimal approach depends on the pathogen, sample type, and research objective. The review emphasizes that parasite DNA enrichment is essential for enabling WGS in clinical settings, underscoring the need for protocol standardization and cost-effectiveness analyses to support public health genomic surveillance.

Adaptive sampling↗
PubMed2025

First clinical diagnosis of FAME3 via commercial Long-Read sequencing reveals mosaic repeat expansion in MARCHF6 gene.

Familial Adult Myoclonic Epilepsy type 3 (FAME3) is a rare autosomal dominant disorder characterized by cortical tremor and epilepsy, caused by a noncoding pentanucleotide repeat expansion (TTTTA/TTTCA)n in the MARCHF6 gene. Conventional genetic testing often fails to detect this expansion due to its repetitive structure and intronic location. We evaluated a 61-year-old woman with refractory myoclonic and generalized tonic-clonic seizures, whose prior genetic testing-including exome and genome sequencing-was non-diagnostic. Using PacBio HiFi long-read whole-genome sequencing and the tandem repeat genotyping tool TRGT, we identified a pathogenic MARCHF6 intronic expansion. The proband harbored one allele with 15 TTTTA repeats and a second allele with a compound expansion of 661 TTTTA and 12 TTTCA repeats. Three affected relatives shared similarly expanded alleles, but with increasing repeat size in the latter generations. Importantly, analysis using TRGT-instability revealed repeat mosaicism in all affected individuals, reflected by variability in motif counts across individual sequencing reads. This somatic heterogeneity may contribute to the phenotypic penetrance, variable expressivity and pleiotropism seen in FAME3 disease expression. To our knowledge, this is the first clinical diagnosis of FAME3 using a commercially available long-read sequencing platform, underscoring its diagnostic utility in resolving complex repeat expansion disorders and uncovering biologically relevant mosaicism.

Humans↗
PubMed2005

A comparative amplification of five different genomic regions on Coxsackie A and B viruses. Implications in clinical diagnostics.

Modern molecular approaches in Human Enterovirus detection rely on the designing of generic and often degenerate primers in order to amplify specific sequences within the enterovirus genome. In the present study a comparative application of primer sets targeting 5'UTR, the VP1 region, the 3D region as well as a long genomic fragment including the 3'end of VP1, the full length of 2A and 2B, and the 5' moiety of the 2C-coding region was attempted, in order to evaluate their specificity and suitability. The best amplification results from the investigation of 21 CAV reference strains, all six CBV reference strains and 44 clinical strains varying in origin and time of isolation, arose using primer sets 292-222 and UC53-UG52. Based on the above results we conclude that some of the published protocols need to be improved so as to fulfill the demands of an accurate detection and typing of Coxsackie A and B viruses. Contrarily, two of the protocols applied were proved to be more accurate in terms of specificity and general applicability, suggesting that RT-PCR followed by a simple RFLP assay in the case of primer pair UC53-UG52 or by sequencing and sequence analysis in the case of primer set 292-222 should constitute alternative means of modern typing and diagnostics against conventional immunological classification methods.

5' Untranslated Regions↗
PubMed2026

Characterization of endogenous pararetroviruses in yam (Dioscorea spp.) genomes revealed four pararetrovirus groups, including a dioscovirus-like lineage: implications for diagnostics and yam germplasm exchange.

Yams (Dioscorea spp.) are an important vegetatively propagated food security crop grown for their starchy tubers. Yams are susceptible to several viruses, and their genomes harbor a diverse array of endogenous pararetroviral sequences (EPRVs), which complicate diagnostics and germplasm exchange because of their similarity to episomal viruses. To better characterize EPRV diversity, we analyzed 86 publicly available whole-genome sequences from five Dioscorea species (D. rotundata, D. alata, D. praehensilis, D. abyssinica, and D. dumetorum). Assembled genomes were screened for endogenous pararetrovirus sequences (EPRVs) using the CAULIFINDER pipeline, targeting conserved RT/RNase H domains of the Caulimoviridae family. Our analyses revealed four major EPRV groups in D. rotundata: Yendovirus, Badnavirus, Yam Endovirus 1, and a Dioscovirus-like lineage. While most insertions were fragmented, we found full-length putative viral genomes corresponding to the Yam Badnavirus and Dioscovirus-like clades. These findings expand knowledge of yam EPRV diversity, contribute to the development of improved diagnostic tools to differentiate endogenous and episomal forms, and promote a science-based, risk-proportionate approach to yam phytosanitation that facilitates global germplasm exchange while maintaining biosecurity.

Dioscorea↗
PubMed2002

Characterization of the intragenomic spread of the human endogenous retrovirus family HERV-W.

This study examines the intragenomic spread of the human endogenous retrovirus family HERV-W from insertions present within the draft sequence of the human genome. Identification of shared diagnostic differences and phylogenetic analyses revealed the existence of three main subfamilies. The average divergence between sequences for each of the subfamilies suggests that most of the HERV-W elements were inserted within the genome during a short period of evolutionary time. Each one of the subfamilies consists of two types of insertions, the expected proviral sequences and other sequences resembling the structure of processed retrogenes. These HERV-W retrosequences extend from the R region of the 5' long-terminal repeat (LTR) to the R region of the 3' LTR (as viral genomic RNAs), end in poly(A) 3' tails, and are flanked by direct repeats longer than the proviral integrations. Furthermore, several of the HERV-W retrosequences are 5'-truncated at different sites. I suggest the involvement of the L1 machinery in these integrations and discuss the characteristic features of the evolutionary history of HERV-W, with emphasis on the putative impact of HERV-W retrosequence integrations on the mammalian genome.

Base Sequence↗
PubMed2005

Diagnostic value of fluorescence in situ hybridization for the detection of genomic aberrations in older patients with acute myeloid leukemia.

BACKGROUND AND OBJECTIVES: Karyotype is one of the most important prognostic factors in acute myeloid leukemia (AML). DESIGN AND METHODS: To assess the diagnostic value of molecular cytogenetics in AML patients older than 60 years, we compared the results of chromosome banding with those of fluorescence in situ hybridization (FISH) applying a comprehensive DNA-probe set for the detection of the most relevant AML-associated chromosome aberrations in a prospective series of 283 patients registered for the multicenter treatment trial AML HD98-B. RESULTS: Four cases of inv(16)/t(16;16) and 2 cases of t(11q23) were only detected by FISH. Molecular cytogenetic analysis was also more sensitive for the detection of genomic imbalances, in particular 7q-, +11q, 17p-, and 20q-, but virtually all cases of aneuploidy or deletions that were missed on banding analysis were identified in patients without assessable metaphases, in patients with normal karyotypes but poor chromosome morphology, in patients with a leukemia-specific balanced rearrangement, or in patients with complex karyotypes. INTERPRETATION AND CONCLUSIONS: Our results support the use of FISH as a complementary method for the detection of inv(16)/t(16;16) and t(11q23) in all older AML patients eligible for intensive therapy. Molecular cytogenetics should also be considered in cases with insufficient yields of metaphase cells, poor chromosome morphology, or both. Routine screening for chromosomal imbalances by FISH does not improve cytogenetic risk assessment in patients with adequate pretreatment karyotype information.

Aged↗
PubMed1994

cDNA cloning of c33-c antigen gene derived from NS3 region of Chinese HCV genome, expression in Escherichia coli and development of HCV EIA second-generation diagnostic kit.

A cDNA fragment of about 860 bp corresponding to the c33-c gene in the non-structural region 3 (NS3) of HCV genome was obtained from one plasma derived from a Chinese HCV carrier who came from Tai' an of Shandong Province, China by the application of reverse transcription (RT) and polymerase chain reaction (PCR) techniques. After the sequence of the cDNA fragment was determined and compared with the equivalent region of the HCV-I (HCV-US) and HCV-II (HCV-BK) genomes, the nucleotide/amino acid sequence homologies were found to be 79.2%/91.3%/ and 91.3%/93.9%, respectively. The prokaryotic expression vector pBV220 was employed for the overproduction of c33-c native recombinant protein in E. coli cells. The expression products were detected by enzyme-linked immunosorbent assay (ELISA) and Western blotting with antisera of chronic hepatitis C patients, and a molecular weight 31 kD of c33-c viral protein was shown to account for 14% of the total cellular soluble proteins. This product was extracted from the bacterial lysate by lysozyme, Triton X-100 and urea treatment, and purified through ion exchange chromatography. The purified c33-c protein combined with a branch peptide MAP-C-19 representing immunodominant epitopes on the nucleocapsid region of HCV genome was used to develop a Chinese HCV EIA 2nd-generation diagnostic kit for the detection of anti-HCV antibodies. Its specificity, sensitivity and reproducibility were all in keeping with the indexes of the national standard for the quality control of the HCV diagnostic kit. The agreement rate between our kit and Abbott company's HCV EIA second-generation diagnostic kit was 99.33%, and the identified rate of positive anti-HCV of our kit was 2% more than that of the Abbott company's kit.

Amino Acid Sequence↗
PubMed2005

Fine mapping of a schizophrenia susceptibility locus at chromosome 6q23: increased evidence for linkage and reduced linkage interval.

We previously reported an autosomal scan for schizophrenia susceptibility loci in a systematically recruited sample of Arab Israeli families. The scan detected significant evidence for linkage at chromosome 6q23 with a nonparametric LOD score (NPL) of 4.60 (P=0.000004) and a multipoint parametric LOD score of 4.16. In order to refine this finding we typed 42 additional microsatellite markers on chromosome 6q between D6S1570 (99.01 cM from the pter) and D6S281 (190.14 from the pter) in the same sample (average intermarker distance approximately 1.7 cM). In the 23 cM region between D6S1715 and D6S311, markers were more closely spaced ( approximately 1.1 cM). Multipoint nonparametric and parametric and single point linkage analyses were performed. The peak NPL rose to 4.98 (P=0.00000058) at D6S1626 (136.97 cM), immediately adjacent to D6S292 (NPL 4.98, P=0.00000068), the marker that gave the highest NPL in the original genome scan, under the broad diagnostic category. The putative susceptibility region (NPL-1) was reduced from 12.0 to 4.96 cM. The peak multipoint parametric LOD score was 4.63 at D6S1626 under a dominant genetic model, core diagnostic category and the LOD-1 interval was 2.10 cM. The maximum single point LOD score (3.55, theta=0.01) was also at D6S1626 (dominant model, core diagnostic category). Increased evidence for linkage in the same sample as in the original genome scan and consistent localization of the linkage peak add further support for the presence of a schizophrenia susceptibility locus at chromosome 6q23. Moreover, the markedly reduced linkage interval greatly improves prospects for identifying a schizophrenia susceptibility gene within the implicated region.

Arabs↗
PubMed2026

Emergence of Fusarium oxysporum f. sp. fragariae in the Eastern United States.

Historically, Fusarium oxysporum f. sp. fragariae (Fof), the causal agent of Fusarium wilt in strawberry, has been a major problem for strawberry production in California but has been largely absent in the rest of the United States. During the growing seasons of 2023 to 2025, independent detections of Fof were made on strawberry plants exhibiting symptoms of Fusarium wilt in the eastern U.S. states of Florida, North Carolina, New York, Connecticut, and Virginia. Sixteen isolates were obtained from symptomatic plants across this region, and a subset (n = 14) were confirmed to be Fof by pathogenicity testing, morphological characterization, PCR diagnostics, and whole-genome sequencing. Specifically, these tests demonstrated that all tested isolates were virulent on susceptible (fw1) strawberry cultivars but not on resistant (FW1) cultivars, classifying them as race 1. Although all isolates tested positive with the more recently developed Fof-specific PCR assay by Burkhardt et al. (2019), many (43.75%) failed detection with the commonly used Suga et al. (2013) assay. Comparative genomics revealed that these isolates represent at least three distinct phylogenetic clades (Y1, Y2, and the putative Y10), suggesting multiple independent introductions rather than a single dissemination event. The genetic diversity of the eastern U.S. Fof populations and their likely origin from nursery stock highlight the need for more robust diagnostics, certified clean planting stock, and region-specific resistance trials to manage Fusarium wilt beyond California.

Fusarium↗
PubMed2005

Use of genome information for the study of the pathogenesis of fungal infections and the development of diagnostic tools.

One of the most exciting advances in Mycology is the application of genomic approaches. The advent of genomics, together with post-genomic studies, promises to revolutionize the studies on the pathogenesis of fungal infections. Approaches include comparative genomics to identify sequences that contribute to infection and disease and functional genomics and proteomics to analyze global patterns of gene and protein expression involved in fungal pathogenesis.

DNA, Fungal↗