Lie Bodies: A Manifold Representation of 3D Human Shape

Abstract. Three-dimensional object shape is commonly represented in terms of deformations of a triangular mesh from an exemplar shape. Ex-isting models, however, are based on a Euclidean representation of shape deformations. In contrast, we argue that shape has a manifold structure: For example, summing the shape deformations for two people does not necessarily yield a deformation corresponding to a valid human shape, nor does the Euclidean difference of these two deformations provide a meaningful measure of shape dissimilarity. Consequently, we define a novel manifold for shape representation, with emphasis on body shapes, using a new Lie group of deformations. This has several advantages. First we define triangle deformations exactly, removing non-physical deforma-tions and redundant degrees of freedom common to previous methods. Second, the Riemannian structure of Lie Bodies enables a more mean-ingful definition of body shape similarity by measuring distance between bodies on the manifold of body shape deformations. Third, the group structure allows the valid composition of deformations. This is important for models that factor body shape deformations into multiple causes or represent shape as a linear combination of basis shapes. Finally, body shape variation is modeled using statistics on manifolds. Instead of mod-eling Euclidean shape variation with Principal Component Analysis we capture shape variation on the manifold using Principal Geodesic Analy-sis. Our experiments show consistent visual and quantitative advantages of Lie Bodies over traditional Euclidean models of shape deformation and our representation can be easily incorporated into existing methods

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Herd-level risk factors associated with cow mortality in Swedish dairy herds

An increase in on-farm mortality (euthanasia and death) in dairy herds has been reported in several countries in the last decade. This does not only imply possible problems with animal welfare, but it also causes economic losses to the farmer. The objective of this study was to evaluate time trends in on-farm dairy cow mortality in Sweden and identify potential herd-level risk factors. Data was retrieved on all Swedish dairy herds enrolled in the milk recording scheme between 2002 and 2010. Herds with a herd size of 40 dead or euthanized cows per 100 cow-years were excluded. Two different models were used: 1 multiple year analysis which included 6,898 herds during the period 2002 to 2010 and 1 single year analysis including 4,252 herds for the year 2010, where other variables that were not present during the entire multiple year study were analyzed. The outcome variable was the number of euthanized and dead cows per year and season. A negative binomial regression model, adjusted for clustering within herd, was applied to both models. Fixed effects in the multiple year analysis were breed, calving interval, herd size, milk yield, region, season, pasture period, and year. Fixed effects in the single year analysis were breed, calving interval, conventional vs. organic farming, herd size, housing system, milk yield, region, and season. The multiple year analysis demonstrated that MR gradually increased from 5.1 to 6.6 events per 100 cow-years during the study period. Swedish MR are consequently on par with, or even greater than, MR among dairy herds in other comparable countries. Higher mortality was associated with larger herd size, longer calving intervals, and herds that had Swedish Holstein as the predominant breed. Lower mortality was observed in herds with a higher herd average milk yield, during the fall and winter, and in organically managed herds. There were regional differences in mortality. An interaction between herd size and season was found in both models. Also, an interaction between housing system and milk yield was found in the single year analysis. This first assessment of on-farm mortality in Swedish dairy herds confirmed that the MR has increased over the last few years. The study also identified some herd-level risk factors

Exponential Barycenters of the Canonical Cartan Connection and Invariant Means on Lie Groups

International audienceWhen performing statistics on elements of sets that possess a particular geometric structure, it is desirable to respect this structure. For instance in a Lie group, it would be judicious to have a notion of a mean which is stable by the group operations (composition and inversion). Such a property is ensured for Riemannian center of mass in Lie groups endowed with a bi-invariant Riemannian metric, like compact Lie groups (e.g. rotations). However, bi-invariant Riemannian metrics do not exist for most non compact and non-commutative Lie groups. This is the case in particular for rigid-body transformations in any dimension greater than one, which form the most simple Lie group involved in biomedical image registration. In this paper, we propose to replace the Riemannian metric by an affine connection structure on the group. We show that the canonical Cartan connections of a connected Lie group provides group geodesics which are completely consistent with the composition and inversion. With such a non-metric structure, the mean cannot be defined by minimizing the variance as in Riemannian Manifolds. However, the characterization of the mean as an exponential barycenter gives us an implicit definition of the mean using a general barycentric equation. Thanks to the properties of the canonical Cartan connection, this mean is naturally bi-invariant. We show the local existence and uniqueness of the invariant mean when the dispersion of the data is small enough. We also propose an iterative fixed point algorithm and demonstrate that the convergence to the invariant mean is at least linear. In the case of rigid-body transformations, we give a simple criterion for the global existence and uniqueness of the bi-invariant mean, which happens to be the same as for rotations. We also give closed forms for the bi-invariant mean in a number of simple but instructive cases, including 2D rigid transformations. For general linear transformations, we show that the bi-invariant mean is a generalization of the (scalar) geometric mean, since the determinant of the bi-invariant mean is the geometric mean of the determinants of the data. Finally, we extend the theory to higher order moments, in particular with the covariance which can be used to define a local bi-invariant Mahalanobis distance

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

Renal cell carcinoma(RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival

Somatic Mutational Landscape of Splicing Factor Genes and Their Functional Consequences across 33 Cancer Types

Hotspot mutations in splicing factor genes have been recently reported at high frequency in hematological malignancies, suggesting the importance of RNA splicing in cancer. We analyzed whole-exome sequencing data across 33 tumor types in The Cancer Genome Atlas (TCGA), and we identified 119 splicing factor genes with significant non-silent mutation patterns, including mutation over-representation, recurrent loss of function (tumor suppressor-like), or hotspot mutation profile (oncogene-like). Furthermore, RNA sequencing analysis revealed altered splicing events associated with selected splicing factor mutations. In addition, we were able to identify common gene pathway profiles associated with the presence of these mutations. Our analysis suggests that somatic alteration of genes involved in the RNA-splicing process is common in cancer and may represent an underappreciated hallmark of tumorigenesis

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although the MYC oncogene has been implicated in cancer, a systematic assessment of alterations of MYC, related transcription factors, and co-regulatory proteins, forming the proximal MYC network (PMN), across human cancers is lacking. Using computational approaches, we define genomic and proteomic features associated with MYC and the PMN across the 33 cancers of The Cancer Genome Atlas. Pan-cancer, 28% of all samples had at least one of the MYC paralogs amplified. In contrast, the MYC antagonists MGA and MNT were the most frequently mutated or deleted members, proposing a role as tumor suppressors. MYC alterations were mutually exclusive with PIK3CA, PTEN, APC, or BRAF alterations, suggesting that MYC is a distinct oncogenic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such as immune response and growth factor signaling; chromatin, translation, and DNA replication/repair were conserved pan-cancer. This analysis reveals insights into MYC biology and is a reference for biomarkers and therapeutics for cancers with alterations of MYC or the PMN. We present a computational study determining the frequency and extent of alterations of the MYC network across the 33 human cancers of TCGA. These data, together with MYC, positively correlated pathways as well as mutually exclusive cancer genes, will be a resource for understanding MYC-driven cancers and designing of therapeutics