Total Wrist Replacement Outcomes in the Asian Pacific Population - A Single-Centre Result.

Background: Total wrist replacement (TWR) is rarely done in the Asia-Pacific region. The aim of this study is to report the surgical outcomes and experience of TWR in patients with advanced arthritis. Methods: This is a retrospective review of all TWR patients in the Department of Orthopaedics and Traumatology, Prince of Wales Hospital, Hong Kong, which is a university tertiary centre, from January 2004 to March 2023. Recorded demographic parameters include gender, age upon surgery, pathology, types of implants and follow-up period. The surgical outcome parameters include range of motion, grip strength, wrist function assessment, radiological and clinical complications and any related secondary operations. Postoperative X-ray and clinical notes were reviewed. All wrist function assessments were performed by specialised occupational therapists according to protocol. Results: The study included a total of 12 wrists of 10 patients, all Chinese-Asian, with a mean age of 61.4 years at surgery. Larsen grade V arthritis constituted 50% and grade IV 16.7% of the patients, amongst which 33% had volar subluxation. The mean follow-up period was 97.4 months (21-205 months). The mean grip strength was 64.2% of the unaffected side. The mean postoperative Disabilities of Arm, Shoulder and Hand (DASH) score was 41.12% and patient-rated wrist/hand evaluation (PRWE) score 18.0. Complication incidence was 16.67% for loosening, 8.3% for metallosis and 8.3% for infection. One patient required conversion to total wrist arthrodesis due to metallosis. No patient suffered from dislocation, periprosthetic fracture and infection. Conclusions: TWR is an effective and safe alternative to total wrist arthrodesis with comparable outcomes. Our series outcomes are satisfactory and in line with literature. With meticulous soft tissue release and balancing, volar subluxation can also be corrected and may not be a contraindication. Level of Evidence: Level IV (Therapeutic).

Dangers with cementation under low-viscosity state: Cement arterio-venogram and bone cement implantation syndrome.

Cement arterio-venogram is a rare event with cement extrusion into femoral nutrient vessels. In literature it is known to be benign with no significant clinical sequelae. It is postulated that it is due to high cement implantation pressure, that results in optimal cement filling quality. All previously reported cases were female patients, and it is thought to be a female only phenomenon due to the relatively narrow femoral canal leading to higher pressures during cementation. In this case series we report 3 cases different to existing literature. All 3 patients showed a cement arterio-venogram together with bone cement implantation syndrome and hypotension intraoperatively. It was also observed that during implantation the cement was of low viscosity. We postulate low cement viscosity during implantation with pressurization is also a contributing factor to these phenomena. This case series also demonstrates the first 2 male cases, showing this the even can occur in males too. The cement arteriovenogram is located at 41%-42% femur length which is within the 'third sixth' of the length of the femur. Good cementation techniques and prevention is also highlighted in this report.

Cost, safety, and rehabilitation of same-stage, bilateral total knee replacements compared to two-stage total knee replacements.

BACKGROUND: Many patients experience bilateral knee osteoarthritis and require bilateral total knee replacement (TKR). Same-stage, bilateral TKR is proposed to be a cost-effective and safe solution compared to two-stage, but conflicting results in the literature are reported. We aim to compare the costs, safety, and rehabilitation performance of patients in same-stage versus two-stage, bilateral TKR with our centre's perioperative protocol. MATERIALS AND METHODS: We retrospectively reviewed 175 patients (95 same-stage, 80 two-stage) who had undergone bilateral TKR in our centre. Patient selection for same-stage, bilateral TKR was strictly protocol-driven and required fulfilment of all criteria, including age < 75 years, American Society of Anesthesiologists (ASA) grade 1 or 2, body mass index (BMI) < 40, and having non-complex arthritis. All patients followed a standardised pre-operative, intra-operative, and post-operative Enhanced Recovery After Surgery (ERAS) protocol. The cost, safety profiles, and rehabilitation outcomes were compared between the same-stage and two-stage groups. RESULTS: The same-stage, bilateral TKR reduced the length of hospital stays by 5.71 days per patient, decreased the operation time by 27.4 min, saved 3.34 (18.6%) physiotherapy sessions, and 3.78 (51.5%) occupational therapy sessions. The same-stage group experienced a higher haemoglobin drop but no significant difference in transfusion percentage, transfusion volume, complication rate, and readmission rate. The two-stage subgroup with anaesthetic risk, age, and BMI similar to the same-stage group showed the same results. Same-stage, bilateral TKR patients experienced no significant difference in final post-operative pain levels and rehabilitation outcomes as two-stage TKR patients. CONCLUSION: This study showed that same-stage, bilateral TKR can reduce costs, with similar safety profiles and rehabilitation outcomes compared to the two-stage, bilateral TKR.

Development of genome-wide polygenic risk scores for lipid traits and clinical applications for dyslipidemia, subclinical atherosclerosis, and diabetes cardiovascular complications among East Asians.

BACKGROUND: The clinical utility of personal genomic information in identifying individuals at increased risks for dyslipidemia and cardiovascular diseases remains unclear. METHODS: We used data from Biobank Japan (n = 70,657-128,305) and developed novel East Asian-specific genome-wide polygenic risk scores (PRSs) for four lipid traits. We validated (n = 4271) and subsequently tested associations of these scores with 3-year lipid changes in adolescents (n = 620), carotid intima-media thickness (cIMT) in adult women (n = 781), dyslipidemia (n = 7723), and coronary heart disease (CHD) (n = 2374 cases and 6246 controls) in type 2 diabetes (T2D) patients. RESULTS: Our PRSs aggregating 84-549 genetic variants (0.251 < correlation coefficients (r) < 0.272) had comparably stronger association with lipid variations than the typical PRSs derived based on the genome-wide significant variants (0.089 < r < 0.240). Our PRSs were robustly associated with their corresponding lipid levels (7.5 × 10- 103 < P < 1.3 × 10- 75) and 3-year lipid changes (1.4 × 10- 6 < P < 0.0130) which started to emerge in childhood and adolescence. With the adjustments for principal components (PCs), sex, age, and body mass index, there was an elevation of 5.3% in TC (ß ± SE = 0.052 ± 0.002), 11.7% in TG (ß ± SE = 0.111 ± 0.006), 5.8% in HDL-C (ß ± SE = 0.057 ± 0.003), and 8.4% in LDL-C (ß ± SE = 0.081 ± 0.004) per one standard deviation increase in the corresponding PRS. However, their predictive power was attenuated in T2D patients (0.183 < r < 0.231). When we included each PRS (for TC, TG, and LDL-C) in addition to the clinical factors and PCs, the AUC for dyslipidemia was significantly increased by 0.032-0.057 in the general population (7.5 × 10- 3 < P < 0.0400) and 0.029-0.069 in T2D patients (2.1 × 10- 10 < P < 0.0428). Moreover, the quintile of TC-related PRS was moderately associated with cIMT in adult women (ß ± SE = 0.011 ± 0.005, Ptrend = 0.0182). Independent of conventional risk factors, the quintile of PRSs for TC [OR (95% CI) = 1.07 (1.03-1.11)], TG [OR (95% CI) = 1.05 (1.01-1.09)], and LDL-C [OR (95% CI) = 1.05 (1.01-1.09)] were significantly associated with increased risk of CHD in T2D patients (4.8 × 10- 4 < P < 0.0197). Further adjustment for baseline lipid drug use notably attenuated the CHD association. CONCLUSIONS: The PRSs derived and validated here highlight the potential for early genomic screening and personalized risk assessment for cardiovascular disease.

Dek Modulates Global Intron Retention during Muscle Stem Cells Quiescence Exit.

Adult stem cells are essential for tissue regeneration. However, the mechanisms underlying the activation of quiescent adult stem cells remain elusive. Using skeletal muscle stem cells, also called satellite cells (SCs), we demonstrate prevalent intron retention (IR) in the transcriptome of quiescent SCs (QSCs). Intron-retained transcripts found in QSCs are essential for fundamental functions including RNA splicing, protein translation, cell-cycle entry, and lineage specification. Further analysis reveals that phosphorylated Dek protein modulates IR during SC quiescence exit. While Dek protein is absent in QSCs, Dek overexpression in vivo results in a global decrease of IR, quiescence dysregulation, premature differentiation of QSCs, and undermined muscle regeneration. Moreover, IR analysis on hundreds of public RNA-seq data show that IR is conserved among quiescent adult stem cells. Altogether, we illustrate IR as a conserved post-transcriptional regulation mechanism that plays an important role during stem cell quiescence exit.

High-Dimensional Single-Cell Cartography Reveals Novel Skeletal Muscle-Resident Cell Populations.

Adult tissue repair and regeneration require stem-progenitor cells that can self-renew and generate differentiated progeny. Skeletal muscle regenerative capacity relies on muscle satellite cells (MuSCs) and their interplay with different cell types within the niche. However, our understanding of skeletal muscle tissue cellular composition is limited. Here, using a combined approach of single-cell RNA sequencing and mass cytometry, we precisely mapped 10 different mononuclear cell types in adult mouse muscle. We also characterized gene signatures and determined key discriminating markers of each cell type. We identified two previously understudied cell populations in the interstitial compartment. One expresses the transcription factor scleraxis and generated tenocytes in vitro. The second expresses markers of smooth muscle and mesenchymal cells (SMMCs) and, while distinct from MuSCs, exhibited myogenic potential and promoted MuSC engraftment following transplantation. The blueprint presented here yields crucial insights into muscle-resident cell-type identities and can be exploited to study muscle diseases.

Large-Scale Expansion of Human iPSC-Derived Skeletal Muscle Cells for Disease Modeling and Cell-Based Therapeutic Strategies.

Although skeletal muscle cells can be generated from human induced pluripotent stem cells (iPSCs), transgene-free protocols include only limited options for their purification and expansion. In this study, we found that fluorescence-activated cell sorting-purified myogenic progenitors generated from healthy controls and Pompe disease iPSCs can be robustly expanded as much as 5 × 1011-fold. At all steps during expansion, cells could be cryopreserved or differentiated into myotubes with a high fusion index. In vitro, cells were amenable to maturation into striated and contractile myofibers. Insertion of acid α-glucosidase cDNA into the AAVS1 locus in iPSCs using CRISPR/Cas9 prevented glycogen accumulation in myotubes generated from a patient with classic infantile Pompe disease. In vivo, the expression of human-specific nuclear and sarcolemmar antigens indicated that myogenic progenitors engraft into murine muscle to form human myofibers. This protocol is useful for modeling of skeletal muscle disorders and for using patient-derived, gene-corrected cells to develop cell-based strategies.

Chlamydia trachomatis Strain Types Have Diversified Regionally and Globally with Evidence for Recombination across Geographic Divides.

Chlamydia trachomatis (Ct) is the leading cause of bacterial sexually transmitted diseases worldwide. The Ct Multi Locus Sequence Typing (MLST) scheme is effective in differentiating strain types (ST), deciphering transmission patterns and treatment failure, and identifying recombinant strains. Here, we analyzed 323 reference and clinical samples, including 58 samples from Russia, an area that has not previously been represented in Ct typing schemes, to expand our knowledge of the global diversification of Ct STs. The 323 samples resolved into 84 unique STs, a 3.23 higher typing resolution compared to the gold standard single locus ompA genotyping. Our MLST scheme showed a high discriminatory index, D, of 0.98 (95% CI 0.97-0.99) confirming the validity of this method for typing. Phylogenetic analyses revealed distinct branches for the phenotypic diseases of lymphogranuloma venereum, urethritis and cervicitis, and a sub-branch for ocular trachoma. Consistent with these findings, single nucleotide polymorphisms were identified that significantly correlated with each phenotype. While the overall number of unique STs per region was comparable across geographies, the number of STs was greater for Russia with a significantly higher ST/sample ratio of 0.45 (95% CI: 0.35-0.53) compared to Europe or the Americas (p < 0.009), which may reflect a higher level of sexual mixing with the introduction of STs from other regions and/or reassortment of alleles. Four STs were found to be significantly associated with a particular geographic region. ST23 [p = 0.032 (95% CI: 1-23)], ST34 [p = 0.019 (95% CI: 1.1-25)]; and ST19 [p = 0.001 (95% CI: 1.7-34.7)] were significantly associated with Netherlands compared to Russia or the Americas, while ST 30 [p = 0.031 (95% CI: 1.1-17.8)] was significantly associated with the Americas. ST19 was significantly associated with Netherlands and Russia compared with the Americans [p = 0.001 (95% CI: 1.7-34.7) and p = 0.006 (95% CI: 1.5-34.6), respectively]. Additionally, recombinant strains were ubiquitous in the data set [106 (32.8%)], although Europe had a significantly higher number than Russia or the Americas (p < 0.04), the majority of which were from Amsterdam [43 (87.8%) of 49)]. The higher number of recombinants in Europe indicates selective pressure and/or adaptive diversification that will require additional studies to elucidate.

OMBlast: alignment tool for optical mapping using a seed-and-extend approach.

Background: Optical mapping is a technique for capturing fluorescent signal patterns of long DNA molecules (in the range of 0.1­1 Mbp). Recently, it has been complementing the widely used short-read sequencing technology by assisting with scaffolding and detecting large and complex structural variations (SVs). Here, we introduce a fast, robust and accurate tool called OMBlast for aligning optical maps, the set of signal locations on the molecules generated from optical mapping. Our method is based on the seed-and-extend approach from sequence alignment, with modifications specific to optical mapping. Results: Experiments with both synthetic and our real data demonstrate that OMBlast has higher accuracy and faster mapping speed than existing alignment methods. Our tool also shows significant improvement when aligning data with SVs. Availability and Implementation: OMBlast is implemented for Java 1.7 and is released under a GPL license. OMBlast can be downloaded from https://github.com/aldenleung/OMBlast and run directly on machines equipped with a Java virtual machine. Contact: kevinyip@cse.cuhk.edu.hk and tf.chan@cuhk.edu.hk Supplementary Information: Supplementary data are available at Bioinformatics online.

Novel Chlamydia trachomatis strains in heterosexual sex partners, Indianapolis, Indiana, USA.

Chlamydia trachomatis causes a high number of sexually transmitted infections worldwide, but reproducible and precise strain typing to link partners is lacking. We evaluated multilocus sequence typing (MLST) for this purpose by detecting sequence types (STs) concordant for the ompA genotype, a single-locus typing standard. We tested samples collected during April 2000-October 2003 from members of established heterosexual partnerships (dyads) in the Indianapolis, Indiana, USA, area who self-reported being coital partners within the previous 30 days. C. trachomatis DNA from 28 dyads was tested by MLST; sequences were aligned and analyzed for ST and phylogenetic relationships. MLST detected 9 C. trachomatis STs, 4 unique to Indianapolis; STs were identical within each dyad. Thirteen unique strains were identified; 9 (32%) dyads harbored novel recombinant strains that phylogenetically clustered with strains comprising the recombinants. The high rate of novel C. trachomatis recombinants identified supports the use of MLST for transmission and strain diversity studies among at-risk populations.

ViralFusionSeq: accurately discover viral integration events and reconstruct fusion transcripts at single-base resolution.

SUMMARY: Insertional mutagenesis from virus infection is an important pathogenic risk for the development of cancer. Despite the advent of high-throughput sequencing, discovery of viral integration sites and expressed viral fusion events are still limited. Here, we present ViralFusionSeq (VFS), which combines soft-clipping information, read-pair analysis and targeted de novo assembly to discover and annotate viral-human fusions. VFS was used in an RNA-Seq experiment, simulated DNA-Seq experiment and re-analysis of published DNA-Seq datasets. Our experiments demonstrated that VFS is both sensitive and highly accurate. AVAILABILITY: VFS is distributed under GPL version 3 at http://hkbic.cuhk.edu.hk/software/viralfusionseq

In vitro recombinants of antibiotic-resistant Chlamydia trachomatis strains have statistically more breakpoints than clinical recombinants for the same sequenced loci and exhibit selection at unexpected loci.

Lateral gene transfer (LGT) is essential for generating between-strain genomic recombinants of Chlamydia trachomatis to facilitate the organism's evolution. Because there is no reliable laboratory-based gene transfer system for C. trachomatis, in vitro generation of recombinants from antibiotic-resistant strains is being used to study LGT. However, selection pressures imposed on in vitro recombinants likely affect statistical properties of recombination relative to naturally occurring clinical recombinants, including prevalence at particular loci. We examined multiple loci for 16 in vitro-derived recombinants of ofloxacin- and rifampin-resistant L(1) and D strains, respectively, grown with both antibiotics, and compared these with the same sequenced loci among 11 clinical recombinants. Breakpoints and recombination frequency were examined using phylogenetics, bioinformatics, and statistics. In vitro and clinical isolates clustered perfectly into two groups, without misclassification, using Ward's minimum variance based on breakpoint data. As expected, gyrA (confers ofloxacin resistance) and rpoB (confers rifampin resistance) had significantly more breakpoints among in vitro recombinants than among clinical recombinants (P < 0.0001 and P = 0.02, respectively, using the Wilcoxon rank sum test). Unexpectedly, trpA also had significantly more breakpoints for in vitro recombinants (P < 0.0001). There was also significant selection at other loci. The strongest bias was for ompA in strain D (P = 3.3 × 10(-8)). Our results indicate that the in vitro model differs statistically from natural recombination events. Additional genomic studies are needed to determine the factors responsible for the observed selection biases at unexpected loci and whether these are important for LGT to inform approaches for genetically manipulating C. trachomatis.

Transformations for the compression of FASTQ quality scores of next-generation sequencing data.

MOTIVATION: The growth of next-generation sequencing means that more effective and efficient archiving methods are needed to store the generated data for public dissemination and in anticipation of more mature analytical methods later. This article examines methods for compressing the quality score component of the data to partly address this problem. RESULTS: We compare several compression policies for quality scores, in terms of both compression effectiveness and overall efficiency. The policies employ lossy and lossless transformations with one of several coding schemes. Experiments show that both lossy and lossless transformations are useful, and that simple coding methods, which consume less computing resources, are highly competitive, especially when random access to reads is needed. AVAILABILITY AND IMPLEMENTATION: Our C++ implementation, released under the Lesser General Public License, is available for download at http://www.cb.k.u-tokyo.ac.jp/asailab/members/rwan. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Hypervirulent Chlamydia trachomatis clinical strain is a recombinant between lymphogranuloma venereum (L(2)) and D lineages.

UNLABELLED: Chlamydia trachomatis is an obligate intracellular bacterium that causes a diversity of severe and debilitating diseases worldwide. Sporadic and ongoing outbreaks of lymphogranuloma venereum (LGV) strains among men who have sex with men (MSM) support the need for research on virulence factors associated with these organisms. Previous analyses have been limited to single genes or genomes of laboratory-adapted reference strain L(2)/434 and outbreak strain L(2)b/UCH-1/proctitis. We characterized an unusual LGV strain, termed L(2)c, isolated from an MSM with severe hemorrhagic proctitis. L(2)c developed nonfusing, grape-like inclusions and a cytotoxic phenotype in culture, unlike the LGV strains described to date. Deep genome sequencing revealed that L(2)c was a recombinant of L(2) and D strains with conserved clustered regions of genetic exchange, including a 78-kb region and a partial, yet functional, toxin gene that was lost with prolonged culture. Indels (insertions/deletions) were discovered in an ftsK gene promoter and in the tarp and hctB genes, which encode key proteins involved in replication, inclusion formation, and histone H1-like protein activity, respectively. Analyses suggest that these indels affect gene and/or protein function, supporting the in vitro and disease phenotypes. While recombination has been known to occur for C. trachomatis based on gene sequence analyses, we provide the first whole-genome evidence for recombination between a virulent, invasive LGV strain and a noninvasive common urogenital strain. Given the lack of a genetic system for producing stable C. trachomatis mutants, identifying naturally occurring recombinants can clarify gene function and provide opportunities for discovering avenues for genomic manipulation. IMPORTANCE: Lymphogranuloma venereum (LGV) is a prevalent and debilitating sexually transmitted disease in developing countries, although there are significant ongoing outbreaks in Australia, Europe, and the United States among men who have sex with men (MSM). Relatively little is known about LGV virulence factors, and only two LGV genomes have been sequenced to date. We isolated an LGV strain from an MSM with severe hemorrhagic proctitis that was morphologically unique in tissue culture compared with other LGV strains. Bioinformatic and statistical analyses identified the strain as a recombinant of L(2) and D strains with highly conserved clustered regions of genetic exchange. The unique culture morphology and, more importantly, disease phenotype could be traced to the genes involved in recombination. The findings have implications for bacterial species evolution and, in the case of ongoing LGV outbreaks, suggest that recombination is a mechanism for strain emergence that results in significant disease pathology.

Adaptive seeds tame genomic sequence comparison.

The main way of analyzing biological sequences is by comparing and aligning them to each other. It remains difficult, however, to compare modern multi-billionbase DNA data sets. The difficulty is caused by the nonuniform (oligo)nucleotide composition of these sequences, rather than their size per se. To solve this problem, we modified the standard seed-and-extend approach (e.g., BLAST) to use adaptive seeds. Adaptive seeds are matches that are chosen based on their rareness, instead of using fixed-length matches. This method guarantees that the number of matches, and thus the running time, increases linearly, instead of quadratically, with sequence length. LAST, our open source implementation of adaptive seeds, enables fast and sensitive comparison of large sequences with arbitrarily nonuniform composition.

Incorporating sequence quality data into alignment improves DNA read mapping.

New DNA sequencing technologies have achieved breakthroughs in throughput, at the expense of higher error rates. The primary way of interpreting biological sequences is via alignment, but standard alignment methods assume the sequences are accurate. Here, we describe how to incorporate the per-base error probabilities reported by sequencers into alignment. Unlike existing tools for DNA read mapping, our method models both sequencer errors and real sequence differences. This approach consistently improves mapping accuracy, even when the rate of real sequence difference is only 0.2%. Furthermore, when mapping Drosophila melanogaster reads to the Drosophila simulans genome, it increased the amount of correctly mapped reads from 49 to 66%. This approach enables more effective use of DNA reads from organisms that lack reference genomes, are extinct or are highly polymorphic.

HAMSTER: visualizing microarray experiments as a set of minimum spanning trees.

BACKGROUND: Visualization tools allow researchers to obtain a global view of the interrelationships between the probes or experiments of a gene expression (e.g. microarray) data set. Some existing methods include hierarchical clustering and k-means. In recent years, others have proposed applying minimum spanning trees (MST) for microarray clustering. Although MST-based clustering is formally equivalent to the dendrograms produced by hierarchical clustering under certain conditions; visually they can be quite different. METHODS: HAMSTER (Helpful Abstraction using Minimum Spanning Trees for Expression Relations) is an open source system for generating a set of MSTs from the experiments of a microarray data set. While previous works have generated a single MST from a data set for data clustering, we recursively merge experiments and repeat this process to obtain a set of MSTs for data visualization. Depending on the parameters chosen, each tree is analogous to a snapshot of one step of the hierarchical clustering process. We scored and ranked these trees using one of three proposed schemes. HAMSTER is implemented in C++ and makes use of Graphviz for laying out each MST. RESULTS: We report on the running time of HAMSTER and demonstrate using data sets from the NCBI Gene Expression Omnibus (GEO) that the images created by HAMSTER offer insights that differ from the dendrograms of hierarchical clustering. In addition to the C++ program which is available as open source, we also provided a web-based version (HAMSTER+) which allows users to apply our system through a web browser without any computer programming knowledge. CONCLUSION: Researchers may find it helpful to include HAMSTER in their microarray analysis workflow as it can offer insights that differ from hierarchical clustering. We believe that HAMSTER would be useful for certain types of gradient data sets (e.g time-series data) and data that indicate relationships between cells/tissues. Both the source and the web server variant of HAMSTER are available from http://hamster.cbrc.jp/.

Predicting phenotype and emerging strains among Chlamydia trachomatis infections.

Chlamydia trachomatis is a global cause of blinding trachoma and sexually transmitted infections (STIs). We used comparative genomics of the family Chlamydiaceae to select conserved housekeeping genes for C. trachomatis multilocus sequencing, characterizing 19 reference and 68 clinical isolates from 6 continental/subcontinental regions. There were 44 sequence types (ST). Identical STs for STI isolates were recovered from different regions, whereas STs for trachoma isolates were restricted by continent. Twenty-nine of 52 alleles had nonuniform distributions of frequencies across regions (p<0.001). Phylogenetic analysis showed 3 disease clusters: invasive lymphogranuloma venereum strains, globally prevalent noninvasive STI strains (ompA genotypes D/Da, E, and F), and nonprevalent STI strains with a trachoma subcluster. Recombinant strains were observed among STI clusters. Single nucleotide polymorphisms (SNPs) were predictive of disease specificity. Multilocus and SNP typing can now be used to detect diverse and emerging C. trachomatis strains for epidemiologic and evolutionary studies of trachoma and STI populations worldwide.

A framework for determining outlying microarray experiments.

Microarrays are high-throughput technologies whose data are known to be noisy. In this work, we propose a graph-based method which first identifies the extent to which a single microarray experiment is noisy and then applies an error function to clean individual expression levels. These two steps are unified within a framework based on a graph representation of a separate data set from some repository. We demonstrate the utility of our method by comparing our results against statistical methods by applying both techniques to simulated microarray data. Our results are encouraging and indicate one potential use of microarray data from past experiments.