Cancer Markers Selection Using Network-Based Cox Regression: A Methodological and Computational Practice.

International initiatives such as the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) are collecting multiple datasets at different genome-scales with the aim of identifying novel cancer biomarkers and predicting survival of patients. To analyze such data, several statistical methods have been applied, among them Cox regression models. Although these models provide a good statistical framework to analyze omic data, there is still a lack of studies that illustrate advantages and drawbacks in integrating biological information and selecting groups of biomarkers. In fact, classical Cox regression algorithms focus on the selection of a single biomarker, without taking into account the strong correlation between genes. Even though network-based Cox regression algorithms overcome such drawbacks, such network-based approaches are less widely used within the life science community. In this article, we aim to provide a clear methodological framework on the use of such approaches in order to turn cancer research results into clinical applications. Therefore, we first discuss the rationale and the practical usage of three recently proposed network-based Cox regression algorithms (i.e., Net-Cox, AdaLnet, and fastcox). Then, we show how to combine existing biological knowledge and available data with such algorithms to identify networks of cancer biomarkers and to estimate survival of patients. Finally, we describe in detail a new permutation-based approach to better validate the significance of the selection in terms of cancer gene signatures and pathway/networks identification. We illustrate the proposed methodology by means of both simulations and real case studies. Overall, the aim of our work is two-fold. Firstly, to show how network-based Cox regression models can be used to integrate biological knowledge (e.g., multi-omics data) for the analysis of survival data. Secondly, to provide a clear methodological and computational approach for investigating cancers regulatory networks

Network-based survival analysis methods for pathway detection in cancer

We compare three penalized Cox regression methods for high-dimensional survival data in order to identify the pathways involved into cancer occurrence and pro- gression. We analyze each method with three gene expression datasets including breast, lung and ovarian cancer. More precisely, we focus on cancer survival prediction and on top signature genes. The goal of this study is to gain a deeper insight of the benefits and drawbacks of the regression techniques in order to find the pathways involved in a specific type of cancer and identify cancer biomarkers useful for prognosis, diagnosis and treatment

Combining Pathway Identification and Breast Cancer Survival Prediction via Screening-Network Methods.

Breast cancer is one of the most common invasive tumors causing high mortality among women. It is characterized by high heterogeneity regarding its biological and clinical characteristics. Several high-throughput assays have been used to collect genome-wide information for many patients in large collaborative studies. This knowledge has improved our understanding of its biology and led to new methods of diagnosing and treating the disease. In particular, system biology has become a valid approach to obtain better insights into breast cancer biological mechanisms. A crucial component of current research lies in identifying novel biomarkers that can be predictive for breast cancer patient prognosis on the basis of the molecular signature of the tumor sample. However, the high dimension and low sample size of data greatly increase the difficulty of cancer survival analysis demanding for the development of ad-hoc statistical methods. In this work, we propose novel screening-network methods that predict patient survival outcome by screening key survival-related genes and we assess the capability of the proposed approaches using METABRIC dataset. In particular, we first identify a subset of genes by using variable screening techniques on gene expression data. Then, we perform Cox regression analysis by incorporating network information associated with the selected subset of genes. The novelty of this work consists in the improved prediction of survival responses due to the different types of screenings (i.e., a biomedical-driven, data-driven and a combination of the two) before building the network-penalized model. Indeed, the combination of the two screening approaches allows us to use the available biological knowledge on breast cancer and complement it with additional information emerging from the data used for the analysis. Moreover, we also illustrate how to extend the proposed approaches to integrate an additional omic layer, such as copy number aberrations, and we show that such strategies can further improve our prediction capabilities. In conclusion, our approaches allow to discriminate patients in high-and low-risk groups using few potential biomarkers and therefore, can help clinicians to provide more precise prognoses and to facilitate the subsequent clinical management of patients at risk of disease

The IASI Water Deficit Index to Monitor Vegetation Stress and Early Drying in Summer Heatwaves: An Application to Southern Italy

The boreal hemisphere has been experiencing increasing extreme hot and dry conditions over the past few decades, consistent with anthropogenic climate change. The continental extension of this phenomenon calls for tools and techniques capable of monitoring the global to regional scales. In this context, satellite data can satisfy the need for global coverage. The main objective we have addressed in the present paper is the capability of infrared satellite observations to monitor the vegetation stress due to increasing drought and heatwaves in summer. We have designed and implemented a new water deficit index (wdi) that exploits satellite observations in the infrared to retrieve humidity, air temperature, and surface temperature simultaneously. These three parameters are combined to provide the water deficit index. The index has been developed based on the Infrared Atmospheric Sounder Interferometer or IASI, which covers the infrared spectral range 645 to 2760 cm−1 with a sampling of 0.25 cm−1. The index has been used to study the 2017 heatwave, which hit continental Europe from May to October. In particular, we have examined southern Italy, where Mediterranean forests suffer from climate change. We have computed the index’s time series and show that it can be used to indicate the atmospheric background conditions associated with meteorological drought. We have also found a good agreement with soil moisture, which suggests that the persistence of an anomalously high water deficit index was an essential driver of the rapid development and evolution of the exceptionally severe 2017 droughts

Optimal Interpolation for Infrared Products from Hyperspectral Satellite Imagers and Sounders

Thermal infrared remote sensing measurements have greatly improved in terms of spectral, spatial, and temporal resolution. These improvements are producing a clearer picture of the land surface and Earth atmospheric composition than ever before. Nevertheless, the analysis of this big quantity of data presents important challenges due to incomplete temporal and spatial recorded information. The aim of the present paper is to discuss a methodology to retrieve missing values of some interesting geophysical variables on a spatial field retrieved from spatially scattered infrared satellite observations in order to yield level 3, regularly gridded, data. The technique is based on a 2-Dimensional (2D) Optimal Interpolation (OI) scheme and is derived from the broad class of Kalman filter or Bayesian estimation theory. The goodness of the approach has been tested on 15-min temporal resolution Spinning Enhanced Visible and Infrared Imager (SEVIRI) emissivity and surface temperature (ST) products over South Italy (land and sea), on Infrared Atmospheric Sounding Interferometer (IASI) atmospheric ammonia ( N H 3 ) concentration over North Italy and carbon monoxide ( C O ), sulfur dioxide ( S O 2 ) and N H 3 concentrations over China. All these gases affect air quality. Moreover, sea surface temperature (SST) retrievals have been compared with gridded data from MODIS (Moderate-resolution Imaging Spectroradiometer) observations. For gases concentration we have considered data from 3 different emission inventories, that is, Emissions Database for Global Atmospheric Research v3.4.2 (EDGARv3.4.2), the Regional Emission inventory in ASiav3.1 (REASv3.1) and MarcoPolov0.1, plus an independent study. The results show the efficacy of the proposed strategy to better capture the daily cycle for surface parameters and to detect hotspots of severe emissions from gas sources affecting air quality such as C O and N H 3 and, therefore, to yield valuable information on the variability of gas concentration to complete ground stations measurements

Convergence for the regularized inversion of Fourier series

AbstractThe problems of smoothing data through a transform in the Fourier domain and of retrieving a function from its Fourier coefficients are analyzed in the present paper. For both of them a solution, based on regularization tools, is known. Aim of the paper is to prove strong results of convergence of the regularized solution and optimality of the Generalized Cross Validation criterion for choosing the regularization parameter

Optimal Interpolation for Infrared Products from Hyperspectral Satellite Imagers and Sounders

Thermal infrared remote sensing measurements have greatly improved in terms of spectral, spatial, and temporal resolution. These improvements are producing a clearer picture of the land surface and Earth atmospheric composition than ever before. Nevertheless, the analysis of this big quantity of data presents important challenges due to incomplete temporal and spatial recorded information. The aim of the present paper is to discuss a methodology to retrieve missing values of some interesting geophysical variables on a spatial field retrieved from spatially scattered infrared satellite observations in order to yield level 3, regularly gridded, data. The technique is based on a 2-Dimensional (2D) Optimal Interpolation (OI) scheme and is derived from the broad class of Kalman filter or Bayesian estimation theory. The goodness of the approach has been tested on 15-min temporal resolution Spinning Enhanced Visible and Infrared Imager (SEVIRI) emissivity and surface temperature (ST) products over South Italy (land and sea), on Infrared Atmospheric Sounding Interferometer (IASI) atmospheric ammonia ( NH3 ) concentration over North Italy and carbon monoxide ( CO ), sulfur dioxide ( SO2 ) and NH3 concentrations over China. All these gases affect air quality. Moreover, sea surface temperature (SST) retrievals have been compared with gridded data from MODIS (Moderate-resolution Imaging Spectroradiometer) observations. For gases concentration we have considered data from 3 different emission inventories, that is, Emissions Database for Global Atmospheric Research v3.4.2 (EDGARv3.4.2), the Regional Emission inventory in ASiav3.1 (REASv3.1) and MarcoPolov0.1, plus an independent study. The results show the efficacy of the proposed strategy to better capture the daily cycle for surface parameters and to detect hotspots of severe emissions from gas sources affecting air quality such as CO and NH3 and, therefore, to yield valuable information on the variability of gas concentration to complete ground stations measurements