Method for Quantum Denoisers Using Convolutional Neural Network.

In many applications of quantum information science, high-dimensional entanglement is needed. Quantum teleportation is used for transferring information from one place to another using Einstein-Podolsk-Rosen pairs (EPR) and two classical bits of communication in a channel. Since we cannot produce multiple copies of an unknown state for amplification, we will generate multiple EPR pairs. However, after the distribution of the EPR pairs, they will have decreased fidelity with the ideal EPR state. So, to maintain the quantum states and maximize the quantification of the entanglement without losing the strength of the states, we propose to denoise the channel for a few types of noise. We created a random noise source and filtered out the irrelevant information without affecting the relevant information encoded in the quantum states. The proposed model is used for successful denoising of GHZ states from spin flips and bit flip errors. Much of the research work is not carried out by using machine-language-based neural networks for noise-reduction in quantum channels. In this paper, we propose a denoiser called quantum denoiser CNQD, which uses a feedforward convolution neural network model. We tuned our model with highly entangled GHZ states with zero phases and phase between [0, ∏] mixed with different kinds of noise. Finally, the proposed model can be used for optimal quantum communication via noisy quantum channels using GHZ states.

Novel Paju Apodemus paramyxovirus 1 and 2, harbored by Apodemus agrarius in the Republic of Korea.

Paramyxoviruses harbored by multiple natural reservoirs pose a potential threat to public health. Jeilongvirus has been proposed as a novel paramyxovirus genus found in rodents, bats, and cats. Paramyxovirus RNA was detected in 108/824 (13.1%) Apodemus agrarius captured at 14 trapping sites in the Republic of Korea. We first present two genetically distinct novel paramyxoviruses, Paju Apodemus paramyxovirus 1 (PAPV-1) and 2 (PAPV-2). The disparity between PAPV-1 (19,716 nucleotides) and -2 (17,475 nucleotides) revealed the presence of the SH gene and length of the G gene in the genome organization. The phylogeny of PAPV-1 and -2 belonged to distinct genetic lineages of Jeilongvirus, respectively, even though these viruses were originated from A. agrarius. PAPV-1 infected human epithelial and endothelial cells, facilitating the induction of type I/III interferons, interferon-stimulated genes, and pro-inflammatory cytokines. Therefore, this study provides insights into the molecular epidemiology, genetic diversity, and virus-host interactions of novel rodent-borne paramyxoviruses.

A case of vocal polyps improved with herbal medicine: A case report.

Vocal polyps are benign vocal cord lesions, which mainly manifest as a hoarse voice. Laryngeal microsurgery is the most common treatment. However, because of anxiety regarding invasive treatment, it is necessary to have a non-invasive treatment option. A 43 year old female patient who is a teacher visited a Korean medical hospital for persistent hoarseness with a vocal polyp. After taking herbal medicine for hoarseness (Kyung-Hee-cheong-um-whan) and pharyngitis (cheong-in-li-gyok-tang and cheong-in-ryu-que-whan) for almost 10 weeks, the vocal polyp was reduced and symptoms improved. Herbal prescription for pharyngitis and hoarseness can be applied to vocal polyps as non-invasive treatment.

Comparing the effects of manual acupuncture, electroacupuncture, and transcutaneous electrical nerve stimulation on chronic tinnitus: a randomized controlled trial.

BACKGROUND: The aim of this study was to investigate the superiority of the effects of manual acupuncture (MA), electroacupuncture (EA), or transcutaneous electrical nerve stimulation (TENS) on chronic consecutive tinnitus. METHODS: Forty-five patients with chronic consecutive tinnitus were allocated into an MA, an EA, or a TENS group at a 1:1:1 ratio. The corresponding patients were treated with MA, EA, or TENS twice a week for 10 sessions (5 weeks). The primary outcome was a change in the tinnitus handicap inventory (THI), and the secondary outcomes were loudness and annoyance of tinnitus, pure-tone audiometry (PTA), and the speech discrimination test. The outcome measures were obtained at baseline, visit 5 (week 3), visit 10 (week 5), and visit 11 (follow-up 4 weeks). RESULTS: Of the 45 participants, 37 (82.22%) completed the study. There was no difference in the THI score change among the groups at any point. However, the number of participants who had reduced scores of more than 10 points was higher in the EA group than in the TENS or MA groups (p = 0.037, Fisher's exact test). There was no significant difference in the loudness and annoyance of tinnitus, PTA, and speech discrimination test findings among the groups. CONCLUSION: Among the MA, EA, and TENS groups, there was no significant difference in the effects on the treatment of chronic consecutive tinnitus. However, EA could respond to more patients. TRIAL REGISTRATION: Registered on October 21, 2016 (KCT0002117 by CRIS).

Cancer classification of single-cell gene expression data by neural network.

MOTIVATION: Cancer classification based on gene expression profiles has provided insight on the causes of cancer and cancer treatment. Recently, machine learning-based approaches have been attempted in downstream cancer analysis to address the large differences in gene expression values, as determined by single-cell RNA sequencing (scRNA-seq). RESULTS: We designed cancer classifiers that can identify 21 types of cancers and normal tissues based on bulk RNA-seq as well as scRNA-seq data. Training was performed with 7398 cancer samples and 640 normal samples from 21 tumors and normal tissues in TCGA based on the 300 most significant genes expressed in each cancer. Then, we compared neural network (NN), support vector machine (SVM), k-nearest neighbors (kNN) and random forest (RF) methods. The NN performed consistently better than other methods. We further applied our approach to scRNA-seq transformed by kNN smoothing and found that our model successfully classified cancer types and normal samples. AVAILABILITY AND IMPLEMENTATION: Cancer classification by neural network. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Commensal microbiota drive the functional diversification of colon macrophages.

Mononuclear phagocytes are a heterogeneous population of leukocytes essential for immune homeostasis that develop tissue-specific functions due to unique transcriptional programs driven by local microenvironmental cues. Single cell RNA sequencing (scRNA-seq) of colonic myeloid cells from specific pathogen free (SPF) and germ-free (GF) C57BL/6 mice revealed extensive heterogeneity of both colon macrophages (MPs) and dendritic cells (DCs). Modeling of developmental pathways combined with inference of gene regulatory networks indicate two major trajectories from common CCR2+ precursors resulting in colon MP populations with unique transcription factors and downstream target genes. Compared to SPF mice, GF mice had decreased numbers of total colon MPs, as well as selective proportional decreases of two major CD11c+CD206intCD121b+ and CD11c-CD206hiCD121b- colon MP populations, whereas DC numbers and proportions were not different. Importantly, these two major colon MP populations were clearly distinct from other colon MP populations regarding their gene expression profile, localization within the lamina propria (LP) and ability to phagocytose macromolecules from the blood. These data uncover the diversity of intestinal myeloid cell populations at the molecular level and highlight the importance of microbiota on the unique developmental as well as anatomical and functional fates of colon MPs.

HNRNPH1-dependent splicing of a fusion oncogene reveals a targetable RNA G-quadruplex interaction.

The primary oncogenic event in ∼85% of Ewing sarcomas is a chromosomal translocation that generates a fusion oncogene encoding an aberrant transcription factor. The exact genomic breakpoints within the translocated genes, EWSR1 and FLI1, vary; however, in EWSR1, breakpoints typically occur within introns 7 or 8. We previously found that in Ewing sarcoma cells harboring EWSR1 intron 8 breakpoints, the RNA-binding protein HNRNPH1 facilitates a splicing event that excludes EWSR1 exon 8 from the EWS-FLI1 pre-mRNA to generate an in-frame mRNA. Here, we show that the processing of distinct EWS-FLI1 pre-mRNAs by HNRNPH1, but not other homologous family members, resembles alternative splicing of transcript variants of EWSR1 We demonstrate that HNRNPH1 recruitment is driven by guanine-rich sequences within EWSR1 exon 8 that have the potential to fold into RNA G-quadruplex structures. Critically, we demonstrate that an RNA mimetic of one of these G-quadruplexes modulates HNRNPH1 binding and induces a decrease in the growth of an EWSR1 exon 8 fusion-positive Ewing sarcoma cell line. Finally, we show that EWSR1 exon 8 fusion-positive cell lines are more sensitive to treatment with the pan-quadruplex binding molecule, pyridostatin (PDS), than EWSR1 exon 8 fusion-negative lines. Also, the treatment of EWSR1 exon 8 fusion-positive cells with PDS decreases EWS-FLI1 transcriptional activity, reversing the transcriptional deregulation driven by EWS-FLI1. Our findings illustrate that modulation of the alternative splicing of EWS-FLI1 pre-mRNA is a novel strategy for future therapeutics against the EWSR1 exon 8 containing fusion oncogenes present in a third of Ewing sarcoma.

Delayed recovery of pediatric sudden sensorineural hearing loss treated with acupuncture: A case report.

RATIONALE: The rate of spontaneous recovery of sudden sensorineural hearing loss (SSNHL) has been reported to be as high as 32% to 65%. Although the majority of spontaneous recoveries occur within 2 weeks, treatment of refractory SSNHL failing conventional therapy is difficult. In particular, it is more difficult to treat children-who have a worse prognosis than adults-with SSNHL refractory to conventional therapy. No studies reported delayed recovery of pediatric SSNHL later than 3 months after onset, or delayed recovery treated with acupuncture. PATIENT CONCERNS: A 15-year-old girl experienced hearing loss after acquiring a cold. DIAGNOSIS: She did not undergo audiometry and only took medicine for a common cold after diagnosis by an internal medicine doctor. Ninety-three days after onset, she visited an otorhinolaryngology clinic and was diagnosed with SSNHL. Seven rounds of intratympanic steroid (ITS) treatment were performed 93 to 135 days after onset; audiogram at 149 days did not demonstrate improvement. INTERVENTIONS: Two-hundred sixty-six days after onset, she visited to TKM hospital and was admitted for 21 days and received outpatient treatment for 1 month after discharge. She was treated acupuncture, transcutaneous electrical nerve stimulation, and moxibustion. OUTCOMES: She experienced improvement in experienced improvement in pure tone average, speech recognition threshold, and word recognition scores after acupuncture treatment. Delayed ITS treatment at 93 to 135 days after onset did not improve the patient's hearing loss. However, slight recovery was achieved at the conclusion of treatment. LESSONS: Acupuncture may be a therapeutic option for individuals who do not experience improvement after the use of steroids or miss early treatment.

Murine pre-B-cell ALL induces T-cell dysfunction not fully reversed by introduction of a chimeric antigen receptor.

Adoptive transfer of patient-derived T cells modified to express chimeric antigen receptors (CARTs) has demonstrated dramatic success in relapsed/refractory pre-B-cell acute lymphoblastic leukemia (ALL), but response and durability of remission requires exponential CART expansion and persistence. Tumors are known to affect T-cell function, but this has not been well studied in ALL and in the context of chimeric antigen receptor (CAR) expression. Using TCF3/PBX1 and MLL-AF4-driven murine ALL models, we assessed the impact of progressive ALL on T-cell function in vivo. Vaccines protect against TCF3/PBX1.3 but were ineffective when administered after leukemia injection, suggesting immunosuppression induced early during ALL progression. T cells from leukemia-bearing mice exhibited increased expression of inhibitory receptors, including PD1, Tim3, and LAG3, and were dysfunctional following adoptive transfer in a model of T-cell receptor (TCR)-dependent leukemia clearance. Although expression of inhibitory receptors has been linked to TCR signaling, pre-B-cell ALL induced inhibitory receptor expression, at least in part, in a TCR-independent manner. Finally, introduction of a CAR into T cells generated from leukemia-bearing mice failed to fully reverse poor in vivo function.

In situ transcriptome characteristics are lost following culture adaptation of adult cardiac stem cells.

Regenerative therapeutic approaches for myocardial diseases often involve delivery of stem cells expanded ex vivo. Prior studies indicate that cell culture conditions affect functional and phenotypic characteristics, but relationship(s) of cultured cells derived from freshly isolated populations and the heterogeneity of the cultured population remain poorly defined. Functional and phenotypic characteristics of ex vivo expanded cells will determine outcomes of interventional treatment for disease, necessitating characterization of the impact that ex vivo expansion has upon isolated stem cell populations. Single-cell RNA-Seq profiling (scRNA-Seq) was performed to determine consequences of culture expansion upon adult cardiac progenitor cells (CPCs) as well as relationships with other cell populations. Bioinformatic analyses demonstrate that identity marker genes expressed in freshly isolated cells become undetectable in cultured CPCs while low level expression emerges for thousands of other genes. Transcriptional profile of CPCs exhibited greater degree of similarity throughout the cultured population relative to freshly isolated cells. Findings were validated by comparative analyses using scRNA-Seq datasets of various cell types generated by multiple scRNA-Seq technology. Increased transcriptome diversity and decreased population heterogeneity in the cultured cell population may help account for reported outcomes associated with experimental and clinical use of CPCs for treatment of myocardial injury.

Optimizing acupuncture treatment for dry eye syndrome: a systematic review.

BACKGROUND: In a former meta-analysis review, acupuncture was considered a potentially effective treatment for dry eye syndrome (DES), but there were heterogeneities among the outcomes. We updated the meta-analysis and conducted subgroup analysis to reduce the heterogeneity and suggest the most effective acupuncture method based on clinical trials. METHODS: We searched for randomized controlled trials (RCTs) in 10 databases (MEDLINE, EMBASE, CENTAL, AMED, SCOPUS, CNKI, Wangfang database, Oriental Medicine Advanced Searching Integrated System (OASIS), Koreamed, J-stage) and searched by hand to compare the effects of acupuncture and artificial tears (AT). We also conducted subgroup analysis by (1) method of intervention (acupuncture only or acupuncture plus AT), (2) intervention frequency (less than 3 times a week or more than 3 times a week), (3) period of treatment (less than 4 weeks or more than 4 weeks), and (4) acupoints (BL1, BL2, ST1, ST2, TE23, Ex-HN5). The Bucher method was used for subgroup comparisons. RESULTS: Nineteen studies with 1126 patients were included. Significant improvements on the Schirmer test (weighted mean difference[WMD], 2.14; 95% confidence interval[CI], 0.93 to 3.34; p = 0.0005) and break up time (BUT) (WMD, 0.98; 95% CI, 0.79 to 1.18; p < 0.00001) were reported. In the subgroup analysis, acupuncture plus AT treatment had a weaker effect in BUT but a stronger effect on the Schirmer test and a better overall effect than acupuncture alone. For treatment duration, treatment longer than 1 month was more effective than shorter treatment. With regard to treatment frequency, treatment less than three times a week was more effective than more frequent treatment. In the acupoint analysis, acupuncture treatment including the BL2 and ST1 acupoints was less effective than treatment that did not include them. None of those factors reduced the heterogeneity. CONCLUSIONS: Acupuncture was more effective than AT in treating DES but showed high heterogeneity. Intervention differences did not influence the heterogeneity.

The full transcription map of mouse papillomavirus type 1 (MmuPV1) in mouse wart tissues.

Mouse papillomavirus type 1 (MmuPV1) provides, for the first time, the opportunity to study infection and pathogenesis of papillomaviruses in the context of laboratory mice. In this report, we define the transcriptome of MmuPV1 genome present in papillomas arising in experimentally infected mice using a combination of RNA-seq, PacBio Iso-seq, 5' RACE, 3' RACE, primer-walking RT-PCR, RNase protection, Northern blot and in situ hybridization analyses. We demonstrate that the MmuPV1 genome is transcribed unidirectionally from five major promoters (P) or transcription start sites (TSS) and polyadenylates its transcripts at two major polyadenylation (pA) sites. We designate the P7503, P360 and P859 as "early" promoters because they give rise to transcripts mostly utilizing the polyadenylation signal at nt 3844 and therefore can only encode early genes, and P7107 and P533 as "late" promoters because they give rise to transcripts utilizing polyadenylation signals at either nt 3844 or nt 7047, the latter being able to encode late, capsid proteins. MmuPV1 genome contains five splice donor sites and three acceptor sites that produce thirty-six RNA isoforms deduced to express seven predicted early gene products (E6, E7, E1, E1^M1, E1^M2, E2 and E8^E2) and three predicted late gene products (E1^E4, L2 and L1). The majority of the viral early transcripts are spliced once from nt 757 to 3139, while viral late transcripts, which are predicted to encode L1, are spliced twice, first from nt 7243 to either nt 3139 (P7107) or nt 757 to 3139 (P533) and second from nt 3431 to nt 5372. Thirteen of these viral transcripts were detectable by Northern blot analysis, with the P533-derived late E1^E4 transcripts being the most abundant. The late transcripts could be detected in highly differentiated keratinocytes of MmuPV1-infected tissues as early as ten days after MmuPV1 inoculation and correlated with detection of L1 protein and viral DNA amplification. In mature warts, detection of L1 was also found in more poorly differentiated cells, as previously reported. Subclinical infections were also observed. The comprehensive transcription map of MmuPV1 generated in this study provides further evidence that MmuPV1 is similar to high-risk cutaneous beta human papillomaviruses. The knowledge revealed will facilitate the use of MmuPV1 as an animal virus model for understanding of human papillomavirus gene expression, pathogenesis and immunology.

The work-relatedness at a case of acute lymphoblastic leukemia in a radiation oncologist.

BACKGROUND: Clinicians who perform radiation therapy (RT) are exposed to radiation, which may negatively affect their health. The present study reports a case of acute lymphoblastic leukemia in a healthcare provider who was exposed to radiation at work; we also present a literature review of this topic. CASE PRESENTATION: A 45-year-old patient, who had been a radiation oncologist and had been exposed to radiation while performing brachytherapy 10 years ago, complained of chest pain and was suspected of having leukemia based on the results of a blood test in an outpatient clinic. He was diagnosed with acute lymphoblastic leukemia, and subsequently underwent chemotherapy. However, the case died during treatment. Through epidemiological investigation, it was found that the case's cumulative exposure dose based on personal exposure and spatial dose measured during the work period was in the range of 6.08-12.15 mSv. CONCLUSIONS: Based on the following considerations, acute lymphoblastic leukemia was highly correlated with the level of radiation to which the case was exposed while performing brachytherapy on patients with cancer. Firstly, the latent period of acute lymphoblastic leukemia in the case closely matched the latency time reported in previous published studies (5-10 years). In addition, numerous studies have reported significantly higher relative risks of cancer among clinicians who perform RT compared with the general population. The case was also atypically exposed to radiation through his hands, despite wearing protective equipment. Lastly, the case's coworkers were also found to have been exposed to high levels of radiation. Investigation into the influence of radiation exposure through atypical routes during RT on the health of clinicians is recommended.

A comparative study on the effects of systemic manual acupuncture, periauricular electroacupuncture, and digital electroacupuncture to treat tinnitus: A randomized, paralleled, open-labeled exploratory trial.

BACKGROUND: Many previous studies of electroacupuncture used combined therapy of electroacupuncture and systemic manual acupuncture, so it was uncertain which treatment was effective. This study evaluated and compared the effects of systemic manual acupuncture, periauricular electroacupuncture and distal electroacupuncture for treating patients with tinnitus. METHODS: A randomized, parallel, open-labeled exploratory trial was conducted. Subjects aged 20-75 years who had suffered from idiopathic tinnitus for > 2 weeks were recruited from May 2013 to April 2014. The subjects were divided into three groups by systemic manual acupuncture group (MA), periauricular electroacupuncture group (PE), and distal electroacupuncture group (DE). The groups were selected by random drawing. Nine acupoints (TE 17, TE21, SI19, GB2, GB8, ST36, ST37, TE3 and TE9), two periauricular acupoints (TE17 and TE21), and four distal acupoints (TE3, TE9, ST36, and ST37) were selected. The treatment sessions were performed twice weekly for a total of eight sessions over 4 weeks. Outcomes were the tinnitus handicap inventory (THI) score and the loud and uncomfortable visual analogue scales (VAS). Demographic and clinical characteristics of all participants were compared between the groups upon admission using one-way analysis of variance (ANOVA). One-way ANOVA was used to evaluate the THI, VAS loud, and VAS uncomfortable scores. The least significant difference test was used as a post-hoc test. RESULTS: Thirty-nine subjects were eligible and their data were analyzed. No difference in THI and VAS loudness scores was observed in between groups. The VAS uncomfortable scores decreased significantly in MA and DE compared with those in PE. Within the group, all three treatments showed some effect on THI, VAS loudness scores and VAS uncomfortable scores after treatment except DE in THI. CONCLUSIONS: There was no statistically significant difference between systemic manual acupuncture, periauricular electroacupuncture and distal electroacupuncture in tinnitus. However, all three treatments had some effect on tinnitus within the group before and after treatment. Systemic manual acupuncture and distal electroacupuncture have some effect on VAS uncomfortable. TRIAL REGISTRATION: KCT0001991 by CRIS (Clinical Research Information Service), 2016-8-1, retrospectively registered.

O-GlcNAcase Is an RNA Polymerase II Elongation Factor Coupled to Pausing Factors SPT5 and TIF1ß.

We describe here the identification and functional characterization of the enzyme O-GlcNAcase (OGA) as an RNA polymerase II elongation factor. Using in vitro transcription elongation assays, we show that OGA activity is required for elongation in a crude nuclear extract system, whereas in a purified system devoid of OGA the addition of rOGA inhibited elongation. Furthermore, OGA is physically associated with the known RNA polymerase II (pol II) pausing/elongation factors SPT5 and TRIM28-KAP1-TIF1ß, and a purified OGA-SPT5-TIF1ß complex has elongation properties. Lastly, ChIP-seq experiments show that OGA maps to the transcriptional start site/5' ends of genes, showing considerable overlap with RNA pol II, SPT5, TRIM28-KAP1-TIF1ß, and O-GlcNAc itself. These data all point to OGA as a component of the RNA pol II elongation machinery regulating elongation genome-wide. Our results add a novel and unexpected dimension to the regulation of elongation by the insertion of O-GlcNAc cycling into the pol II elongation regulatory dynamics.

Purification, sequencing and evaluation of a divergent phytase from Penicillium oxalicum KCTC6440.

A fungal strain producing high levels of phytase was purified to homogeneity from Penicillium oxalicum KCTC6440 (PhyA). The molecular mass of the purified PhyA was 65 kDa and optimal activity occurred at 55°C. The enzyme was stable in a pH range of 4.5-6.5, with an optimum performance at pH 5.5. The Km value for the substrate sodium phytate was 0.48 mM with a Vmax of 672 U/mg. The enzyme was inhibited by Ca(2+), Cu(2+), and Zn(2+), and slightly enhanced by EDTA. The PhyA efficiently released phosphate from feedstuffs such as soybean, rich bran and corn meal. The PhyA gene was cloned in two steps of degenerate PCR and inverse PCR and found to comprise 1501 bp and encode 461 amino acid residues. The enzyme was found to have only 13 amino acids differing to the known PhyA from other Penicillium sp., but has distinct enzyme characteristics. Computational analysis showed that PhyA possessed more positively charged residues in the active sites compared to other PhyA molecules, which may explain the broader pH spectrum.

Biosignals analysis for kidney function effect analysis of fennel aromatherapy.

Human effort in order to enjoy a healthy life is diverse. IT technology to these analyzes, the results of development efforts, it has been applied. Therefore, I use the care and maintenance diagnostic health management and prevention than treatment. In particular, the aromatherapy treatment easy to use without the side effects there is no irritation, are widely used in modern society. In this paper, we measured the aroma effect by applying a biosignal analysis techniques; an experiment was performed to analyze. In particular, we design methods and processes of research based on the theory aroma that affect renal function. Therefore, in this paper, measuring the biosignals and after fennel aromatherapy treatment prior to the enforcement of the mutual comparison, through the analysis, studies were carried out to analyze the effect of fennel aromatherapy therapy on kidney function.

The effect of organisational system on self-rated depression in a panel of male municipal firefighters.

OBJECTIVES: The present study evaluated the effects of job stress, including organisational system to self-rated depression through a panel study of male municipal firefighters in the Republic of Korea. METHODS: A panel of 186 municipal firefighters reported self-rated depressive symptoms according to the Beck Depression Inventory (BDI). The effects of job stress were evaluated using the Korea Occupational Stress Scale, taken one year earlier and classified by the median value. Panel members were classified into Depression or Control groups according to BDI scores, with a cut-off level of 'over mild depression' in a follow-up survey. RESULTS: The Depression group included 17 (9.1%) workers. Firefighters who scored high on occupational system had an 8.3 times greater risk of being assigned to the Depression group than those who had not (adjusted odds ratio [OR] = 8.03, 95% confidence interval (CI) = [1.73-37.22]). In contrast, job stress from a 'difficult physical environment' revealed negative risks related to being classified in the Depression group (AOR = 0.20, 95% CI = [0.04-0.92]). CONCLUSIONS: Although the healthy worker effect may be involved, job stress based on perceptions of organisational system was a strong risk factor for depression. A comprehensive approach should be considered that encompasses social issues when assessing or mental health in high-risk groups, as well as the practical issue of physiochemical hazards.

ECOD: an evolutionary classification of protein domains.

Understanding the evolution of a protein, including both close and distant relationships, often reveals insight into its structure and function. Fast and easy access to such up-to-date information facilitates research. We have developed a hierarchical evolutionary classification of all proteins with experimentally determined spatial structures, and presented it as an interactive and updatable online database. ECOD (Evolutionary Classification of protein Domains) is distinct from other structural classifications in that it groups domains primarily by evolutionary relationships (homology), rather than topology (or "fold"). This distinction highlights cases of homology between domains of differing topology to aid in understanding of protein structure evolution. ECOD uniquely emphasizes distantly related homologs that are difficult to detect, and thus catalogs the largest number of evolutionary links among structural domain classifications. Placing distant homologs together underscores the ancestral similarities of these proteins and draws attention to the most important regions of sequence and structure, as well as conserved functional sites. ECOD also recognizes closer sequence-based relationships between protein domains. Currently, approximately 100,000 protein structures are classified in ECOD into 9,000 sequence families clustered into close to 2,000 evolutionary groups. The classification is assisted by an automated pipeline that quickly and consistently classifies weekly releases of PDB structures and allows for continual updates. This synchronization with PDB uniquely distinguishes ECOD among all protein classifications. Finally, we present several case studies of homologous proteins not recorded in other classifications, illustrating the potential of how ECOD can be used to further biological and evolutionary studies.