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- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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- Bulik, CM, et al.
(författare)
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The changing "weightscape" of bulimia nervosa
- 2012
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Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 169:10, s. 1031-1036
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Tidskriftsartikel (refereegranskat)
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- Romagnoni, A, et al.
(författare)
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Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10351-
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Tidskriftsartikel (refereegranskat)abstract
- Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.
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- Zerwas, SC, et al.
(författare)
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CBT4BN: A Randomized Controlled Trial of Online Chat and Face-to-Face Group Therapy for Bulimia Nervosa
- 2017
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Ingår i: Psychotherapy and psychosomatics. - : S. Karger AG. - 1423-0348 .- 0033-3190. ; 86:1, s. 47-53
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Objective:</i></b> Although cognitive-behavioral therapy (CBT) represents the first-line evidence-based psychotherapy for bulimia nervosa (BN), most individuals seeking treatment do not have access to this specialized intervention. We compared an Internet-based manualized version of CBT group therapy for BN conducted via a therapeutic chat group (CBT4BN) to the same treatment conducted via a traditional face-to-face group therapy (CBTF2F). <b><i>Method:</i></b> In a two-site, randomized, controlled noninferiority trial, we tested the hypothesis that CBT4BN would not be inferior to CBTF2F. A total of 179 adult patients with BN (2.6% males) received up to 16 sessions of group CBT over 20 weeks in either CBT4BN or CBTF2F, and outcomes were compared at the end of treatment and at the 12-month follow-up. <b><i>Results:</i></b> At the end of treatment, CBT4BN was inferior to CBTF2F in producing abstinence from binge eating and purging. However, by the 12-month follow-up, CBT4BN was mostly not inferior to CBTF2F. Participants in the CBT4BN condition, but not CBTF2F, continued to reduce their binge-eating and purging frequency from the end of treatment to the 12-month follow-up. <b><i>Conclusions:</i></b> CBT delivered online in a group chat format appears to be an efficacious treatment for BN, although the trajectory of recovery may be slower than face-to-face group therapy. Online chat groups may increase accessibility of treatment and represent a cost-effective approach to service delivery. However, barriers in service delivery such as state-specific license and ethical guidelines for online therapists need to be addressed.
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