Relative Comparison Kernel Learning with Auxiliary Kernels

In this work we consider the problem of learning a positive semidefinite kernel matrix from relative comparisons of the form: "object A is more similar to object B than it is to C", where comparisons are given by humans. Existing solutions to this problem assume many comparisons are provided to learn a high quality kernel. However, this can be considered unrealistic for many real-world tasks since relative assessments require human input, which is often costly or difficult to obtain. Because of this, only a limited number of these comparisons may be provided. In this work, we explore methods for aiding the process of learning a kernel with the help of auxiliary kernels built from more easily extractable information regarding the relationships among objects. We propose a new kernel learning approach in which the target kernel is defined as a conic combination of auxiliary kernels and a kernel whose elements are learned directly. We formulate a convex optimization to solve for this target kernel that adds only minor overhead to methods that use no auxiliary information. Empirical results show that in the presence of few training relative comparisons, our method can learn kernels that generalize to more out-of-sample comparisons than methods that do not utilize auxiliary information, as well as similar methods that learn metrics over objects

What Is the Important Point Related to Follow-Up Sonographic Evaluation for the Developmental Dysplasia of the Hip?

Developmental dysplasia of the hip (DDH) is an important cause of childhood disability. Subluxation or dislocation can be diagnosed through pediatric physical examination; nevertheless, the ultrasonographic examination is necessary in diagnosing certain borderline cases. It has been evaluated routine sonographic examination of 2,444 hips of 1,222 babies to determine differences in both, developmental dysplasia and types of hips, and evaluated their development on the 3-month follow-up. Evaluating the pathologic alpha angles under 59, there was no statistically significant differences between girls and boys in both right (55.57 +/- 3.73) (56.20 +/- 4.01), (p = 0.480), and left (55.79 +/- 3.96) (57.00 +/- 3.84), (p = 0.160) hips on the 45th day of life. Routine sonographic examinations on the 45th day of life revealed that 51 of (66.2%) 77 type 2a right hips were girls and 26 (33.8%) were boys. The number of the right hips that develop into type 1 was 38 (74.5%) for girls and 26 (100%) for boys on the 90th day of life (p = 0.005). A total of 87 type 2a left hips included 64 girls (73.6%) and 23 boys (26.4%). In the 90th day control, 49 right hip of girls (76.6%) and 21 right hip of boys (91.3%) developed into type 1 (p = 0.126). In the assessment of both left and right hips, girls showed a significantly higher frequency in latency and boys showed significantly higher development in the control sonography. A total of 31 girls (2.5%) and 11 boys (0.9%) accounted for a total of 42 (3.4%) cases who showed bilateral type 2a hips in 1,222 infants. On the 90th day control, 26 girls (83.9%) and all 11 boys (100%) developed into type 1 (p = 0.156). The study emphasizes the importance of the sonographic examination on the 90th day of life. Results of the investigation include the data of sonographic screening of DDH on the 45th day, and also stress the importance of the 90th-day control sonography after a close follow-up with physical examination between 45th and 90th days of life

Multi-Target Prediction: A Unifying View on Problems and Methods

Multi-target prediction (MTP) is concerned with the simultaneous prediction of multiple target variables of diverse type. Due to its enormous application potential, it has developed into an active and rapidly expanding research field that combines several subfields of machine learning, including multivariate regression, multi-label classification, multi-task learning, dyadic prediction, zero-shot learning, network inference, and matrix completion. In this paper, we present a unifying view on MTP problems and methods. First, we formally discuss commonalities and differences between existing MTP problems. To this end, we introduce a general framework that covers the above subfields as special cases. As a second contribution, we provide a structured overview of MTP methods. This is accomplished by identifying a number of key properties, which distinguish such methods and determine their suitability for different types of problems. Finally, we also discuss a few challenges for future research

Time to Recurrence and Survival in Serous Ovarian Tumors Predicted from Integrated Genomic Profiles

Serous ovarian cancer (SeOvCa) is an aggressive disease with differential and often inadequate therapeutic outcome after standard treatment. The Cancer Genome Atlas (TCGA) has provided rich molecular and genetic profiles from hundreds of primary surgical samples. These profiles confirm mutations of TP53 in ∼100% of patients and an extraordinarily complex profile of DNA copy number changes with considerable patient-to-patient diversity. This raises the joint challenge of exploiting all new available datasets and reducing their confounding complexity for the purpose of predicting clinical outcomes and identifying disease relevant pathway alterations. We therefore set out to use multi-data type genomic profiles (mRNA, DNA methylation, DNA copy-number alteration and microRNA) available from TCGA to identify prognostic signatures for the prediction of progression-free survival (PFS) and overall survival (OS). prediction algorithm and applied it to two datasets integrated from the four genomic data types. We (1) selected features through cross-validation; (2) generated a prognostic index for patient risk stratification; and (3) directly predicted continuous clinical outcome measures, that is, the time to recurrence and survival time. We used Kaplan-Meier p-values, hazard ratios (HR), and concordance probability estimates (CPE) to assess prediction performance, comparing separate and integrated datasets. Data integration resulted in the best PFS signature (withheld data: p-value = 0.008; HR = 2.83; CPE = 0.72).We provide a prediction tool that inputs genomic profiles of primary surgical samples and generates patient-specific predictions for the time to recurrence and survival, along with outcome risk predictions. Using integrated genomic profiles resulted in information gain for prediction of outcomes. Pathway analysis provided potential insights into functional changes affecting disease progression. The prognostic signatures, if prospectively validated, may be useful for interpreting therapeutic outcomes for clinical trials that aim to improve the therapy for SeOvCa patients

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies

Large-scale optimization with the primal-dual column generation method

The primal-dual column generation method (PDCGM) is a general-purpose column generation technique that relies on the primal-dual interior point method to solve the restricted master problems. The use of this interior point method variant allows to obtain suboptimal and well-centered dual solutions which naturally stabilizes the column generation. As recently presented in the literature, reductions in the number of calls to the oracle and in the CPU times are typically observed when compared to the standard column generation, which relies on extreme optimal dual solutions. However, these results are based on relatively small problems obtained from linear relaxations of combinatorial applications. In this paper, we investigate the behaviour of the PDCGM in a broader context, namely when solving large-scale convex optimization problems. We have selected applications that arise in important real-life contexts such as data analysis (multiple kernel learning problem), decision-making under uncertainty (two-stage stochastic programming problems) and telecommunication and transportation networks (multicommodity network flow problem). In the numerical experiments, we use publicly available benchmark instances to compare the performance of the PDCGM against recent results for different methods presented in the literature, which were the best available results to date. The analysis of these results suggests that the PDCGM offers an attractive alternative over specialized methods since it remains competitive in terms of number of iterations and CPU times even for large-scale optimization problems.Comment: 28 pages, 1 figure, minor revision, scaled CPU time