1169 results for "NHMRC+youth+mental+health+evaluation+2010..2025+Australia"

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• NHLBI TOPMed: SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS)

  Subpopulations and Intermediate Outcome Measures in COPD Study Description Subpopulations and intermediate outcome measures in COPD study (SPIROMICS) supports the prospective collection and analysis of phenotypic, biomarker, genetic, genomic, and clinical data from subjects with COPD for the purpose of identifying subpopulations and intermediate outcome measures. It is funded by the National Heart, Lung, and Blood Institute and is coordinated by the University of North Carolina at Chapel Hill. Molecular fingerprinting and extensive subject phenotyping will be performed to identify disease subpopulations and to identify and validate surrogate markers of disease severity, which will be useful as intermediate outcome measures for future clinical trials. Secondary aims are to clarify the natural history of COPD, to develop bioinformatic resources that will enable the utilization and sharing of data in studies of COPD and related diseases, and to create a collection of clinical, biomarker, radiographic, and genetic data that can be used by external investigators for other studies of COPD. Participating Institutions: Research participants for SPIROMICS will be enrolled, phenotyped, and followed at twelve SPIROMICS Clinical Centers: Columbia University, Temple University, Johns Hopkins University, Wake Forest University, University of Michigan, University of Illinois at Chicago, University of Iowa, University of Utah, National Jewish Health, University of California at San Francisco, and University of California at Los Angeles. The University of North Carolina at Chapel Hill serves as the Genomics and Informatics Center. The Radiology Reading Center is based at the University of Iowa. The PFT Reading Center is based at the University of California at Los Angeles. Study Design: SPIROMICS is a prospective cohort study that enrolled approximately 2,981 participants at twelve clinical centers over five years. Participants are distributed across four enrollment strata (i.e., Never-smokers, Smokers without COPD, Mild/Moderate COPD, and Severe COPD). Study Visits: Participants have up to four in-person visits (Baseline and Annual Clinic Visits at years 1, 2, 3 after Baseline). Study questionnaires and spirometry are completed at all main study visits. Blood and urine samples are collected at visits 1, 2, and 4. Sputum samples are collected at Visit 1. The CT scans are completed and Baseline and Visit 2. Participants also receive quarterly follow-up calls to assess health status and determine if an exacerbation has occurred. Substudies Bronchoscopy and Immunophenotyping Substudy The Bronchoscopy Substudy will enroll 50 subjects per site, for a total of 300 participants. These participants will be recruited across all four study strata. This substudy includes two study visits. During the first visit, sputum samples are collected for Immunophenotyping analysis at the Immunophenotyping Core Lab based at the University of Michigan. Participants then return for a second visit during which samples are collected via bronchoscopy, including bronchoalveolar lavage, epithelial brushings and bronchial biopsies. Immunophenotyping analysis is also conducted on BAL and blood collected during the bronchoscopy study visit. Repeatability Substudy The entire baseline clinic visit was repeated on 98 volunteers to determine reliability of measurement procedures. All baseline study-related procedures and questionnaires, including the CT scan, were re-administered and new samples of blood, urine, saliva, and sputum were collected. Field center staff processed these biospecimen samples according to the same protocol. Exacerbation Substudy The Exacerbation Substudy is a prospective, longitudinal observational study of up to 400 participants, which will allow the assessment of participant-driven health care utilization (HCU) events and symptom-defined exacerbation events over time. HCU-driven events are defined by change in medical treatment in response to a perceived COPD Exacerbation. Symptom-based events will be defined by using EXACT-PRO (EXacerbations of Chronic Pulmonary Disease Tool - Patient Reported Outcome), a daily symptom diary developed to measure the frequency, severity, and duration of exacerbations in clinical trials. All participants are provided with a PDA on which to complete the diary. Participants reporting a possible COPD exacerbation will be brought into the study clinic for a study visit to collect biological specimens and questionnaire data. The overall objectives of the Exacerbation Substudy are to: Obtain clinical data and specimens on SPIROMICS participants before and during an acute COPD exacerbation defined by Health care utilization triggered by the subject, or Symptomatic change (triggered by an EXACT defined threshold) Describe symptomatic changes occurring around HCU and symptom-defined (EXACT) events and their relationship to clinical and specimen data, Characterize the non-exacerbation "stable" state in COPD using the EXACT, including: Symptom variability (EXACT), Clinical data and specimen parameters during a stable state (baseline), The relationship between clinical and specimen data and symptom severity and variability. Explore the characteristics of stable patients, defined as those who do not experience HCU or symptom-defined (EXACT) events during the sub-study period, using baseline clinical data and specimens, and compare these characteristics with patients who experience HCU and/or symptom-defined events. Examine the relationship between HCU and symptom-defined exacerbation frequency during the first one-year period of follow-up for exacerbations and health outcomes, including 12-month change in lung function and COPD health status, and longer-term morbidity and mortality, with the latter derived from long-term data from the larger SPIROMICS study.

  Study phs001927

• Clinical and Genetic Evaluation of Individuals with Undiagnosed Disorders through the Undiagnosed Diseases Network (UDN)

  The National Human Genome Research Institute and the NIH Clinical Center established the intramural Undiagnosed Diseases Program (UDP) in 2008 to make progress in uncovering, understanding, and treating rare disorders. Based on the success of the UDP, the NIH Common Fund established the Undiagnosed Diseases Network (UDN) in FY 2013 (Phase I, 9/16/2015-8/31/2018) to achieve this type of cross-disciplinary approach to disease diagnosis in academic medical centers around the United States. The NIH Common Fund expanded the network in 2018 (Phase II, 9/1/2018-6/20/2023) to increase the availability of diagnostic services, foster opportunities for collaboration between laboratory and clinical investigators, provide resulting data and protocols to the broader community, and assess development of a sustainable national resource after Common Fund support ends. The UDN transitioned from Common Fund in 2023. The National Institute of Neurological Disorders and Stroke (NINDS) will oversee the Network in Phase III, which launched in July 2023, with help from 17 different NIH Institutes and Centers along with the NIH Office of the Director. With help from patients, family members, patient advocacy groups, a Data Management and Coordinating Center (DMCC), several Clinical Sites, and other stakeholders, the NIH envisions the UDN evolving into a larger, diverse, and self-sustained network that fosters scientific discovery and provides expert diagnostic services for undiagnosed patients across the nation. The overarching goals of the UDN in Phase III include: Continuing the proven success of the UDN in improving the clinical evaluation of difficult-to-diagnose patients using a collaborative team approach and investigating and validating promising new diagnostic technologies. Facilitating research into the etiology of undiagnosed diseases by collecting and sharing standardized, high-quality clinical and laboratory data including genotyping, phenotyping, and documentation of environmental exposures. Promoting a broader integrated and collaborative community across multiple Clinical Sites and among laboratory and clinical investigators prepared to investigate the genetic, pathophysiologic, cell biologic, and molecular mechanisms underpinning these difficult-to-diagnose conditions.

  Study phs001232

• Lung Cancer Genetic Study Among Asian Never Smokers

  The Lung Cancer Genetic Study Among Asian Never Smokers includes data from four population-based studies conducted among Asian women: the Shanghai Women's Health Study (SWHS), the Hwasun Cancer Epidemiology Study (HCES1 and HCES2), the Female Lung Cancer Consortium in Asia (FLCCA, including sFLCA), and the Guangzhou Lung Cancer Study (GLCS). Shanghai Women's Health Study (SWHS): The SWHS is a population-based prospective cohort study of approximately 75,000 adult women who were recruited between 1997 and 2000. The cohort has been followed by a combination of record linkage and active follow-ups. Lung cancer patients identified in the SWHS and non-cases were included in the current study.Hwasun Cancer Epidemiology Study-Lung Cancer (HCES1 and HCES2): The HCES is a hospital-based case-control study whose goal is to identify factors of the cancer development and clinical progression in a Korean population. Included in this project were 299 female lung cancer cases from HCES2, who were diagnosed between April 2004 and February 2013 at Chonnam National University Hwasun Hospital, a cancer specified hospital in Jeollanam-do province, South Korea. Controls were randomly selected from women with no previous cancer diagnosis at enrollment in the Namwon Study and the Dong-gu study, ongoing community-based cohort studies in South Korea. A total of 1,103 controls (273 from HCES1 and 830 from HCES2) were genotyped by MEGA. Guangzhou Lung Cancer Study (GLCS): The GLCS is a case-control study including never-smoking women lung cancer cases and controls from Guangzhou, China.In this study, the DNA samples of 1,195 subjects from SWHS and GLCS were genotyped using whole exome sequencing (WES), and the DNA samples of 7,174 subjects from SWHS, HCES1, HCES2, FLCCA, and sFLCA were genotyped using the Multi-Ethnic Global Array (MEGA).

  Study phs002366

• The Human Phenotype Project (HPP) is a large-scale deep-phenotype prospective longitudinal and ethnically diverse cohort

  The Human Phenotype Project (HPP) is a large-scale deep-phenotype prospective longitudinal and ethnically diverse cohort and biobank that we established. To date, approximately 28,000 participants have enrolled in the study, with over 13,000 having completed their initial visit. The project is aimed at identifying novel molecular signatures with diagnostic, prognostic and therapeutic value, and at developing AI-based predictive models for disease onset and progression. A unique feature of the HPP is its deep and longitudinal profiling that includes medical history, lifestyle and nutritional habits, vital signs, anthropometrics, blood tests, continuous glucose and sleep monitoring, imaging modalities and molecular profiling of the transcriptome, genetics, gut, vaginal and oral microbiome, metabolome and immune system. For several of these modalities, the HPP is the first or largest cohort of its kind. Our analyses of this data provide novel insights into the variation of phenotypes with age and ethnicity, highlighting the importance of having ethnically diverse cohorts and the need for establishing age-dependent norms. We demonstrate how the HPP can be used to unravel personalized molecular signatures of disease by comparison to patient-specific and disease-specific matched healthy controls. Leveraging the extensive dietary and lifestyle HPP data, we systematically identify associations between lifestyle factors and health outcomes. Finally, we present a multi-modal foundation AI model that is trained using self-supervised learning on diet and CGM data and outperforms existing methods in predicting future onset of disease. We extend this AI framework to integrate all data modalities of each subject as a continuous sequence of diverse medical events, creating a digital twin that can simulate interventions and predict health trajectories and outcomes.

  Study EGAS00001008040

• Longitudinal cfDNA methylome and fragmentome profiles in health

  This dataset contains 432 plasma cfDNA samples from healthy individuals, comprising a diurnal cohort of 16 participants and a cross-sectional cohort of 144 participants. Samples underwent capture-based target enrichment using a custom probe set covering 4,991 genomic regions, followed by targeted enzymatic methyl-sequencing on Illumina instruments in 150 bp paired-end mode. The dataset consists of raw FASTQ files generated from the sequencing runs, accompanied by a metadata file containing individual demographic details and sampling information.

  Dataset EGAD50000001721

• May 2019 data update (fastq) for reference epigenomes generated at Centre for Epigenome Mapping Technologies, Genome Sciences Center, B.C. Cancer Agency as part of the International Human Epigenome Consortium.

  May 2019 data update (fastq) for reference epigenomes generated at Centre for Epigenome Mapping Technologies (Canadian Epigenetics, Environment and Health Research Consortium), Genome Sciences Center, B.C. Cancer Agency, Vancouver, Canada as part of the International Human Epigenome Consortium.

  Dataset EGAD00001005060

• August 2020 data update (fastq) for reference epigenomes generated at Centre for Epigenome Mapping Technologies, Genome Sciences Center, B.C. Cancer Agency as part of the International Human Epigenome Consortium.

  August 2020 data update (fastq) for reference epigenomes generated at Centre for Epigenome Mapping Technologies (Canadian Epigenetics, Environment and Health Research Consortium), Genome Sciences Center, B.C. Cancer Agency, Vancouver, Canada as part of the International Human Epigenome Consortium.

  Dataset EGAD00001006383

• August 2019 data update (fastq) for reference epigenomes generated at Centre for Epigenome Mapping Technologies, Genome Sciences Center, B.C. Cancer Agency as part of the International Human Epigenome Consortium.

  August 2019 data update (fastq) for reference epigenomes generated at Centre for Epigenome Mapping Technologies (Canadian Epigenetics, Environment and Health Research Consortium), Genome Sciences Center, B.C. Cancer Agency, Vancouver, Canada as part of the International Human Epigenome Consortium.

  Dataset EGAD00001005335

• Udated data for October 2017 data release for reference epigenomes generated at Centre for Epigenome Mapping Technologies, Genome Sciences Center, B.C. Cancer Agency as part of the International Human Epigenome Consortium.

  October 2017 data update (bam/fastq) for reference epigenomes generated at Centre for Epigenome Mapping Technologies (Canadian Epigenetics, Environment and Health Research Consortium), Genome Sciences Center, B.C. Cancer Agency, Vancouver, Canada as part of the International Human Epigenome Consortium.

  Dataset EGAD00001003906

• January 2018 data update (bam/fastq) for reference epigenomes generated at Centre for Epigenome Mapping Technologies, Genome Sciences Center, B.C. Cancer Agency as part of the International Human Epigenome Consortium.

  January 2018 data update (bam/fastq) for reference epigenomes generated at Centre for Epigenome Mapping Technologies (Canadian Epigenetics, Environment and Health Research Consortium), Genome Sciences Center, B.C. Cancer Agency, Vancouver, Canada as part of the International Human Epigenome Consortium.

  Dataset EGAD00001003962

• June 2017 data update (bam/fastq) for reference epigenomes generated at Centre for Epigenome Mapping Technologies, Genome Sciences Center, B.C. Cancer Agency as part of the International Human Epigenome Consortium.

  June 2017 data update (bam/fastq) for reference epigenomes generated at Centre for Epigenome Mapping Technologies (Canadian Epigenetics, Environment and Health Research Consortium), Genome Sciences Center, B.C. Cancer Agency, Vancouver, Canada as part of the International Human Epigenome Consortium.

  Dataset EGAD00001003414

• September 2016 data update (bam/fastq/vcf) for reference epigenomes generated at Centre for Epigenome Mapping Technologies, Genome Sciences Center, B.C. Cancer Agency as part of the International Human Epigenome Consortium.

  September 2016 data update (bam/fastq/vcf) for reference epigenomes generated at Centre for Epigenome Mapping Technologies (Canadian Epigenetics, Environment and Health Research Consortium), Genome Sciences Center, B.C. Cancer Agency, Vancouver, Canada as part of the International Human Epigenome Consortium.

  Dataset EGAD00001002724

• March 2016 update of Whole genome bisulfite sequencing assay data (bams) for reference epigenomes generated at Centre for Epigenome Mapping Technologies, Genome Sciences Center, B.C. Cancer Agency as part of the International Human Epigenome Consortium.

  March 2016 update of Whole genome bisulfite sequencing assay data (bams) for reference epigenomes generated at Centre for Epigenome Mapping Technologies (Canadian Epigenetics, Environment and Health Research Consortium), Genome Sciences Center, B.C. Cancer Agency, Vancouver, Canada as part of the International Human Epigenome Consortium.

  Dataset EGAD00001001987

• Collaborative Study of Genes, Nutrients and Metabolites (CSGNM)

  While many genetic and metabolic studies focus on understanding disease states, this genome wide association study (GWAS) was designed to understand the influence of genetic variants on circulating metabolites and factors in normal, healthy individuals. Over 2500 healthy, ethnically Irish college students attending Trinity College Dublin completed a health and diet questionnaire and provided a non-fasting blood sample to be used for genetic and metabolic analysis. The questionnaire was designed to collect information on age, sex, height, weight, medical conditions, smoking, dietary habits, and consumption of alcohol, fortified foods, and supplements. Extracted DNA was genotyped using the Illumina HumanOmni1-Quad Beadchip. Metabolites were measured using a number of methods and focused on those relevant to the folate/vitamin B12 pathway.

  Study phs000789

• Pharmacogenomics of Metformin Dose Response in T2DM Patients

  Type 2 Diabetes Mellitus (T2DM) is a chronic and sometimes debilitating disease that affects millions of adults in the USA. Metformin is commonly prescribed for T2DM; yet some T2DM patients do not tolerate it or respond well. This pharmacogenomics study will examine response, as both change in T2DM patients' weight and hemoglobin A1c (HbA1c) levels, to different doses of metformin, by extracting this data from the electronic health record (EHR), for T2DM subjects taking metformin found by prescription orders in the EHR, and identified as cases with the EHR phenotype algorithm published by Kho et. al. in 2012 (PMID: 22101970 as part of the eMERGE (electronic Medical Records and Genomics; dbGaP phs000237, phs000297, phs000360, phs000368, phs000888, and phs000948) project.

  Study phs000984

• Synchronous patterning of hiPSC-derived CNS progenitors generates comprehensive axial spinal cord organoids (CASCOs) containing diverse motor neuron population

  Advancements in human induced pluripotent stem cell (hiPSC) culture have enabled the generation of spinal cord organoids (SCOs), though achieving distinct axial identities in spinal motor neurons (spMNs) along the rostro-caudal (RC) axis remains a challenge. By optimizing the timing and sequence of patterning factors, we developed a mixed stem cell model of rostral neural stem cells (NSCs) and caudal neuromesodermal progenitors (NMPs) to generate SCOs with enhanced spMN heterogeneity, including a wide range of axial identities and benchmarked this against commonly used protocols. Our approach, termed CASO (Comprehensive Axial Spinal Organoids), also incorporates endothelial networks and skeletal muscle to improve organoid complexity and health, offering a novel method to study spMN axial specification and model neurodegenerative diseases.

  Study EGAS50000000891

• The acute effects of morning bright light on the human white adipose tissue transcriptome: exploratory post hoc analysis

  The circadian rhythm of the central brain clock in the suprachiasmatic nucleus (SCN) is synchronized by light. White adipose tissue (WAT) is one of the metabolic endocrine organs containing a molecular clock, and it is synchronized by the SCN; excess WAT is a risk factor for health issues including type 2 diabetes mellitus (DM2). We hypothesized that bright-light exposure would affect the human WAT transcriptome. Therefore, we analyzed WAT biopsies from two previously performed randomized cross-over trials (trial 1: lean healthy men, and trial 2: men with obesity and DM2). RNA sequencing results showed major group differences between men with obesity and DM2 and lean healthy men, as well as a differential effect of bright light exposure.

  Study EGAS50000001206

• Spatial map of microglia states across CNS diseases

  Microglia are the key immune cells involved in virtually all diseases of the central nervous system (CNS). Here, we generated a novel large-scale single-cell RNA-sequencing-derived taxonomy through the analysis of > 1 million CNS cells enriched for myeloid cells across > 15 different pathologies and conditions. Disease-associated human microglia, together with CNS-associated macrophages and monocytes, were differentiated iteratively into 27 superclusters and 192 clusters. This top-down approach, in combination with targeted and genome-wide subcellular spatial transcriptomics, enabled us to examine and compare the spatial interactome of the identified superclusters and clusters within and across pathologies. Our data provide new insights into the spatial dynamics of the endogenous CNS immune system during development, health and disease in humans.

  Study EGAS50000001289

• H3Africa - An integrated approach to the identification of genetic determinants of susceptibility to trypanosomiasis

  The over-arching aim of this network is to improve the health of people living in some of the poorest countries in the world that carry a disproportionate burden of infectious diseases. Despite their importance, the study of many tropical diseases has lagged behind that of diseases of developed countries. This network will redress the balance by performing high quality research into two neglected tropical diseases, human African Trypanosomiasis (HAT) and schistosomiasis. Our aim is to investigate the genetic determinants of the human reservoirs of HAT and schistosomiasis, filling an important knowledge gap, while extending and strengthening the underpinning infrastructure to deliver these scientific objectives in particular by developing the next generation of African geneticists.

  Study EGAS00001007173

• Natural History, Pathogenesis and Outcome of Melorheostosis

  Melorheostosis is a rare osteosclerotic disease resulting in exuberant excessive bone growth with a characteristic radiographic appearance often described as "dripping candle wax". As a result of these bony formations, patients report mild to moderate pain that interferes with their routine activities. It is usually diagnosed on radiographs but bone biopsy may be performed to exclude other osteosclerotic diseases and/or osteosarcoma. Deformities, limb-length discrepancy, muscle atrophy, neurological deficit have been reported as complications. A subset of patients have somatic mutations in MAP2K1. The cause of this disease is not known in all patients, the natural history poorly described and there is no clearly-defined systemic therapy. We propose a prospective observational study to investigate the natural history and pathogenesis of the disease. Subjects will undergo standardized initial evaluation and medically indicated testing. Skin biopsies may be performed to test for known mutations related to melorheostosis, and if negative affected bone and/or skin may be sent for genetic testing for acquired somatic mutations in genes that control bone homeostasis. Enrolled subjects will be followed every two to three years for assessment of disease progression and receive clinically indicated testing and treatment. The study of this rare bone disease offers the potential to generate new insights, provide answers as well as generate new questions into the biology of the skeletal and mineral metabolism.

  Study phs001976

• Clinical Study of Intermittent Positive Pressure Breathing (IPPB-BioLINCC)

  Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions. Objectives: To evaluate the efficacy of long-term intermittent positive pressure breathing (IPPB) treatment when used as an adjunct to the overall care of ambulatory outpatients with chronic obstructive pulmonary disease. The evaluation compared the use of IPPB with use of a powered nebulizer.Participants: A total of 3218 participants were enrolled.Design: Multicenter randomized controlled clinical trial. Conclusions: Compliance with treatment, lung function, and quality of life were evaluated at regular intervals during follow-up, and records were kept of hospitalizations and vital status. Treatment compliance was less than optimal; only half of the participants used their devices for the prescribed amount of time or 10 minutes at least three times a day. Although this was disappointing, it was probably the best compliance that could be attained. There was no statistically significant difference between the treatment groups in mortality, rate and duration of hospitalizations, or change in lung function or life quality with time, overall or for clinically relevant subgroups. The trial group saw no advantage of IPPB over compressor nebulizer therapy and concluded that, if an advantage existed, it must be marginal.

  Study phs004010

• INSPIRE - Investigator-initiated Phase 2 Study of Pembrolizumab Immunological Response in Metastatic Solid Tumors

  Whole exome and RNA sequencing source data for: Clouthier, D.L., Lien, S.C., Yang, S.Y.C. et al. An interim report on the investigator-initiated phase 2 study of pembrolizumab immunological response evaluation (INSPIRE). j. immunotherapy cancer 7, 72 (2019). https://doi.org/10.1186/s40425-019-0541-0 Bratman S*, Yang SYC*, Iafolla MAJ, Liu Z, Hansen AR, Bedard P, Lheureux S, Spreafico A, Razak AA, Shchegrova S, Louie M, Billings P, Zimmerman B, Sethi H, Aleshi A, Torti D, Marsh K, Eagles J, Cirlan I, Hanna Y, Clouthier D, Lien SC, Ohashi PS, Xu W, Siu LL, Pugh TJ. Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab. Nature Cancer. 2020:1:873-881. https://doi.org/10.1038/s43018- 020-0096-5. Yang SYC, Lien SC, Wang BX, Clouthier DL, Hanna Y, Cirlan I, Zhu K, Bruce JP, El Ghamrasni S, Iafallo MAJ, Oliva M, Hansen AR, Spreafico A, Bedard PL, Lheureux S, Razak A, Speers V, Berman HK, Aleshin A, Haibe-Kains B, Brooks DG, McGaha TL, Butler MO, Bratman SV, Ohashi PS, Siu LL, and Pugh TJ. Pan-cancer analysis of longitudinal metastatic tumors reveals genomic alterations and immune landscape dynamics associated with pembrolizumab sensitivity. Nature Comm 2021:12, 5137. https://doi.org/10.1038/s41467-021-25432-7

  Study EGAS00001003280

• A Cancer Cell-Line Titration Series for Evaluating Somatic Classification

  Accurate detection of somatic single nucleotide variants and small insertions and deletions from DNA sequencing experiments of tumour-normal pairs is a challenging task. Tumour samples are often contaminated with normal cells confounding the available evidence for the somatic variants. Furthermore, tumours are heterogeneous so sub-clonal variants are observed at reduced allele frequencies. We present here a cell-line titration series dataset that can be used to evaluate somatic variant calling pipelines with the goal of reliably calling true somatic mutations at low allele frequencies. Cell-line DNA was mixed with matched normal DNA at 8 different ratios to generate samples with known tumour cellularities, and exome sequenced on Illumina HiSeq to depths of >300x. The data was processed with several different variant calling pipelines and verification experiments were performed to assay >1,500 somatic variant candidates using Ion Torrent PGM as an orthogonal technology. By examining the variants called at varying cellularities and depths of coverage, we show that the best performing pipelines are able to maintain a high level of precision at any cellularity. In addition, we estimate the number of true somatic variants undetected as cellularity and coverage decrease. Our cell-line titration series dataset, along with the associated verification results, is effective for this evaluation and will serve as a valuable dataset for future somatic calling algorithm development.

  Study EGAS00001001016

• TRACERx 100: metastatic samples

  Whole exome sequencing of 10 metastatic biopsies from four TRACERx100 patients (see EGA dataset EGAS00001002247), collected either after relapse or death. The data from these samples are initially published with Abbosh, C. et al. Phylogenetic ctDNA analysis depicts early stage lung cancer evolution. Nature http://dx.doi.org/10.1038/nature22364 (2017). Abstract: Earlier detection of relapse following primary surgery for non-small cell lung cancer and the characterization of emerging subclones seeding metastatic sites might offer new therapeutic approaches to limit tumor recurrence. The potential to non-invasively track tumor evolutionary dynamics in ctDNA of early-stage lung cancer is not established. Here we conduct a patient-specific approach to ctDNA profiling in the first 100 lung TRACERx (TRAcking Cancer Evolution through therapy (Rx)) study participants, including one patient co-recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release in early-stage non-small cell lung cancer and perform tumor volume limit of detection analyses. Through blinded profiling of post-operative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients destined to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastases, providing a new approach for ctDNA driven therapeutic studies.

  Study EGAS00001002415

• mFAST-SeqS

  Recent progress in the analysis of cell-free DNA fragments (cell-free circulating tumor DNA, ctDNA) now allows monitoring of tumor genomes by non-invasive means. However, previous studies with plasma DNA from patients with cancer demonstrated highly variable allele frequencies of ctDNA. The comprehensive analysis of tumor genomes is greatly facilitated when plasma DNA has increased amounts of ctDNA. Therefore, a fast and cost-effective pre-screening method to identify such plasma samples without previous knowledge about alterations in the respective tumor genome could assist in the selection of samples suitable for further extensive qualitative analysis. To address this, we adapted the recently described FAST-SeqS method, which was originally established as a simple and effective, non-invasive screening method for fetal aneuploidy from maternal blood. We show that our modified FAST-SeqS method (mFAST-SeqS) can be used as a pre-screening tool for an estimation of the ctDNA percentage. Using a combined evaluation of genome-wide and chromosome-arm specific z-scores from dilution series with cell line DNA and by comparisons of plasma-Seq profiles with data from mFAST-SeqS, we established a detection limit of 10% or more of mutant alleles. Plasma samples with an mFAST-SeqS z-score above 5 showed highly concordant results compared to copy number profiles obtained from our previously described plasma-Seq approach.

  Study EGAS00001001133