TY - JOUR A1 - Mireles, Victor A1 - Conrad, Tim T1 - Reusable building blocks in biological systems JF - Journal of the Royal Society Interface N2 - One of the most widely recognized features of biological systems is their modularity. The modules that constitute biological systems are said to be redeployed and combined across several conditions, thus acting as building blocks. In this work, we analyse to what extent are these building blocks reusable as compared with those found in randomized versions of a system. We develop a notion of decompositions of systems into phenotypic building blocks, which allows them to overlap while maximizing the number of times a building block is reused across several conditions. Different biological systems present building blocks whose reusability ranges from single use (e.g. condition specific) to constitutive, although their average reusability is not always higher than random equivalents of the system. These decompositions reveal a distinct distribution of building block sizes in real biological systems. This distribution stems, in part, from the peculiar usage pattern of the elements of biological systems, and constitutes a new angle to study the evolution of modularity. Y1 - 2018 U6 - https://doi.org/10.1098/rsif.2018.0595 VL - 15 IS - 149 SP - 1 EP - 10 ER - TY - JOUR A1 - Ma, Xiaolin A1 - Conrad, Tim A1 - Alchikh, Maren A1 - Reiche, J. A1 - Schweiger, Brunhilde A1 - Rath, Barbara T1 - Can we distinguish respiratory viral infections based on clinical features? A prospective pediatric cohort compared to systematic literature review JF - Medical Virology N2 - Studies have shown that the predictive value of “clinical diagnoses” of influenza and other respiratory viral infections is low, especially in children. In routine care, pediatricians often resort to clinical diagnoses, even in the absence of robust evidence‐based criteria. We used a dual approach to identify clinical characteristics that may help to differentiate infections with common pathogens including influenza, respiratory syncytial virus, adenovirus, metapneumovirus, rhinovirus, bocavirus‐1, coronaviruses, or parainfluenza virus: (a) systematic review and meta‐analysis of 47 clinical studies published in Medline (June 1996 to March 2017, PROSPERO registration number: CRD42017059557) comprising 49 858 individuals and (b) data‐driven analysis of an inception cohort of 6073 children with ILI (aged 0‐18 years, 56% male, December 2009 to March 2015) examined at the point of care in addition to blinded PCR testing. We determined pooled odds ratios for the literature analysis and compared these to odds ratios based on the clinical cohort dataset. This combined analysis suggested significant associations between influenza and fever or headache, as well as between respiratory syncytial virus infection and cough, dyspnea, and wheezing. Similarly, literature and cohort data agreed on significant associations between HMPV infection and cough, as well as adenovirus infection and fever. Importantly, none of the abovementioned features were unique to any particular pathogen but were also observed in association with other respiratory viruses. In summary, our “real‐world” dataset confirmed published literature trends, but no individual feature allows any particular type of viral infection to be ruled in or ruled out. For the time being, laboratory confirmation remains essential. More research is needed to develop scientifically validated decision models to inform best practice guidelines and targeted diagnostic algorithms. Y1 - 2018 U6 - https://doi.org/10.1002/rmv.1997 VL - 28 IS - 5 SP - 1 EP - 12 ER - TY - JOUR A1 - Alchikh, Maren A1 - Conrad, Tim A1 - Hoppe, Christian A1 - Ma, Xiaolin A1 - Broberg, Eeva K. A1 - Penttinen, P. A1 - Reiche, J. A1 - Biere, Barbara A1 - Schweiger, Brunhilde A1 - Rath, Barbara T1 - Are we missing respiratory viral infections in infants and children? Comparison of a hospital-based quality management system with standard of care. Clinical Microbiology and Infection JF - Clinical Microbiology and Infection Y1 - 2018 U6 - https://doi.org/10.1016/j.cmi.2018.05.023 IS - 06/18 SP - 1 EP - 1 ER - TY - CHAP A1 - Jayrannejad, Fahrnaz A1 - Conrad, Tim T1 - Better Interpretable Models for Proteomics Data Analysis Using rule-based Mining T2 - Springer Lecture Notes in Artificial Intelligence N2 - Recent advances in -omics technology has yielded in large data-sets in many areas of biology, such as mass spectrometry based proteomics. However, analyzing this data is still a challenging task mainly due to the very high dimensionality and high noise content of the data. One of the main objectives of the analysis is the identification of relevant patterns (or features) which can be used for classification of new samples to healthy or diseased. So, a method is required to find easily interpretable models from this data. To gain the above mentioned goal, we have adapted the disjunctive association rule mining algorithm, TitanicOR, to identify emerging patterns from our mass spectrometry proteomics data-sets. Comparison to five state-of-the-art methods shows that our method is advantageous them in terms of identifying the inter-dependency between the features and the TP-rate and precision of the features selected. We further demonstrate the applicability of our algorithm to one previously published clinical data-set. Y1 - 2017 SP - studi ER - TY - CHAP A1 - Tack, Alexander A1 - Zachow, Stefan T1 - Accurate Automated Volumetry of Cartilage of the Knee using Convolutional Neural Networks: Data from the Osteoarthritis Initiative T2 - IEEE 16th International Symposium on Biomedical Imaging (ISBI 2019) N2 - Volumetry of cartilage of the knee is needed for knee osteoarthritis (KOA) assessment. It is typically performed manually in a tedious and subjective process. We developed a method for an automated, segmentation-based quantification of cartilage volume by employing 3D Convolutional Neural Networks (CNNs). CNNs were trained in a supervised manner using magnetic resonance imaging data and cartilage volumetry readings performed by clinical experts for 1378 subjects provided by the Osteoarthritis Initiative. It was shown that 3D CNNs are able to achieve volume measures comparable to the magnitude of variation between expert readings and the real in vivo situation. In the future, accurate automated cartilage volumetry might support both, diagnosis of KOA as well as longitudinal analysis of KOA progression. Y1 - 2019 U6 - https://doi.org/10.1109/ISBI.2019.8759201 SP - 40 EP - 43 ER - TY - GEN A1 - Ambellan, Felix A1 - Tack, Alexander A1 - Ehlke, Moritz A1 - Zachow, Stefan T1 - Automated Segmentation of Knee Bone and Cartilage combining Statistical Shape Knowledge and Convolutional Neural Networks: Data from the Osteoarthritis Initiative (Supplementary Material) T2 - Medical Image Analysis N2 - We present a method for the automated segmentation of knee bones and cartilage from magnetic resonance imaging that combines a priori knowledge of anatomical shape with Convolutional Neural Networks (CNNs). The proposed approach incorporates 3D Statistical Shape Models (SSMs) as well as 2D and 3D CNNs to achieve a robust and accurate segmentation of even highly pathological knee structures. The shape models and neural networks employed are trained using data of the Osteoarthritis Initiative (OAI) and the MICCAI grand challenge "Segmentation of Knee Images 2010" (SKI10), respectively. We evaluate our method on 40 validation and 50 submission datasets of the SKI10 challenge. For the first time, an accuracy equivalent to the inter-observer variability of human readers has been achieved in this challenge. Moreover, the quality of the proposed method is thoroughly assessed using various measures for data from the OAI, i.e. 507 manual segmentations of bone and cartilage, and 88 additional manual segmentations of cartilage. Our method yields sub-voxel accuracy for both OAI datasets. We made the 507 manual segmentations as well as our experimental setup publicly available to further aid research in the field of medical image segmentation. In conclusion, combining statistical anatomical knowledge via SSMs with the localized classification via CNNs results in a state-of-the-art segmentation method for knee bones and cartilage from MRI data. Y1 - 2019 U6 - https://doi.org/10.12752/4.ATEZ.1.0 N1 - OAI-ZIB dataset VL - 52 IS - 2 SP - 109 EP - 118 ER - TY - JOUR A1 - Ambellan, Felix A1 - Tack, Alexander A1 - Ehlke, Moritz A1 - Zachow, Stefan T1 - Automated Segmentation of Knee Bone and Cartilage combining Statistical Shape Knowledge and Convolutional Neural Networks: Data from the Osteoarthritis Initiative JF - Medical Image Analysis N2 - We present a method for the automated segmentation of knee bones and cartilage from magnetic resonance imaging that combines a priori knowledge of anatomical shape with Convolutional Neural Networks (CNNs). The proposed approach incorporates 3D Statistical Shape Models (SSMs) as well as 2D and 3D CNNs to achieve a robust and accurate segmentation of even highly pathological knee structures. The shape models and neural networks employed are trained using data of the Osteoarthritis Initiative (OAI) and the MICCAI grand challenge "Segmentation of Knee Images 2010" (SKI10), respectively. We evaluate our method on 40 validation and 50 submission datasets of the SKI10 challenge. For the first time, an accuracy equivalent to the inter-observer variability of human readers has been achieved in this challenge. Moreover, the quality of the proposed method is thoroughly assessed using various measures for data from the OAI, i.e. 507 manual segmentations of bone and cartilage, and 88 additional manual segmentations of cartilage. Our method yields sub-voxel accuracy for both OAI datasets. We made the 507 manual segmentations as well as our experimental setup publicly available to further aid research in the field of medical image segmentation. In conclusion, combining statistical anatomical knowledge via SSMs with the localized classification via CNNs results in a state-of-the-art segmentation method for knee bones and cartilage from MRI data. Y1 - 2019 U6 - https://doi.org/10.1016/j.media.2018.11.009 VL - 52 IS - 2 SP - 109 EP - 118 ER - TY - JOUR A1 - Shao, Borong A1 - Bjaanaes, Maria A1 - Helland, Aslaug A1 - Schütte, Christof A1 - Conrad, Tim T1 - EMT network-based feature selection improves prognosis prediction in lung adenocarcinoma JF - PLOS ONE N2 - Various feature selection algorithms have been proposed to identify cancer prognostic biomarkers. In recent years, however, their reproducibility is criticized. The performance of feature selection algorithms is shown to be affected by the datasets, underlying networks and evaluation metrics. One of the causes is the curse of dimensionality, which makes it hard to select the features that generalize well on independent data. Even the integration of biological networks does not mitigate this issue because the networks are large and many of their components are not relevant for the phenotype of interest. With the availability of multi-omics data, integrative approaches are being developed to build more robust predictive models. In this scenario, the higher data dimensions create greater challenges. We proposed a phenotype relevant network-based feature selection (PRNFS) framework and demonstrated its advantages in lung cancer prognosis prediction. We constructed cancer prognosis relevant networks based on epithelial mesenchymal transition (EMT) and integrated them with different types of omics data for feature selection. With less than 2.5% of the total dimensionality, we obtained EMT prognostic signatures that achieved remarkable prediction performance (average AUC values above 0.8), very significant sample stratifications, and meaningful biological interpretations. In addition to finding EMT signatures from different omics data levels, we combined these single-omics signatures into multi-omics signatures, which improved sample stratifications significantly. Both single- and multi-omics EMT signatures were tested on independent multi-omics lung cancer datasets and significant sample stratifications were obtained. Y1 - 2019 U6 - https://doi.org/10.1371/journal.pone.0204186 VL - 14 IS - 1 ER - TY - JOUR A1 - Bernard, Florian A1 - Salamanca, Luis A1 - Thunberg, Johan A1 - Tack, Alexander A1 - Jentsch, Dennis A1 - Lamecker, Hans A1 - Zachow, Stefan A1 - Hertel, Frank A1 - Goncalves, Jorge A1 - Gemmar, Peter T1 - Shape-aware Surface Reconstruction from Sparse 3D Point-Clouds JF - Medical Image Analysis N2 - The reconstruction of an object’s shape or surface from a set of 3D points plays an important role in medical image analysis, e.g. in anatomy reconstruction from tomographic measurements or in the process of aligning intra-operative navigation and preoperative planning data. In such scenarios, one usually has to deal with sparse data, which significantly aggravates the problem of reconstruction. However, medical applications often provide contextual information about the 3D point data that allow to incorporate prior knowledge about the shape that is to be reconstructed. To this end, we propose the use of a statistical shape model (SSM) as a prior for surface reconstruction. The SSM is represented by a point distribution model (PDM), which is associated with a surface mesh. Using the shape distribution that is modelled by the PDM, we formulate the problem of surface reconstruction from a probabilistic perspective based on a Gaussian Mixture Model (GMM). In order to do so, the given points are interpreted as samples of the GMM. By using mixture components with anisotropic covariances that are “oriented” according to the surface normals at the PDM points, a surface-based fitting is accomplished. Estimating the parameters of the GMM in a maximum a posteriori manner yields the reconstruction of the surface from the given data points. We compare our method to the extensively used Iterative Closest Points method on several different anatomical datasets/SSMs (brain, femur, tibia, hip, liver) and demonstrate superior accuracy and robustness on sparse data. Y1 - 2017 UR - http://www.sciencedirect.com/science/article/pii/S1361841517300233 U6 - https://doi.org/10.1016/j.media.2017.02.005 VL - 38 SP - 77 EP - 89 ER - TY - JOUR A1 - Sarich, Marco A1 - Djurdjevac Conrad, Natasa A1 - Bruckner, Sharon A1 - Conrad, Tim A1 - Schütte, Christof T1 - Modularity revisited: A novel dynamics-based concept for decomposing complex networks JF - Journal of Computational Dynamics Y1 - 2014 UR - http://publications.mi.fu-berlin.de/1127/ U6 - https://doi.org/10.3934/jcd.2014.1.191 VL - 1 IS - 1 SP - 191 EP - 212 ER -