Discovery and replication of gene influences on brain structure using LASSO regression

We implemented least absolute shrinkage and selection operator (LASSO) regression to evaluate gene effects in genome-wide association studies (GWAS) of brain images, using an MRI-derived temporal lobe volume measure from 729 subjects scanned as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Sparse groups of SNPs in individual genes were selected by LASSO, which identifies efficient sets of variants influencing the data. These SNPs were considered jointly when assessing their association with neuroimaging measures. We discovered 22 genes that passed genome-wide significance for influencing temporal lobe volume. This was a substantially greater number of significant genes compared to those found with standard, univariate GWAS. These top genes are all expressed in the brain and include genes previously related to brain function or neuropsychiatric disorders such as MACROD2, SORCS2, GRIN2B, MAGI2, NPAS3, CLSTN2, GABRG3, NRXN3, PRKAG2, GAS7, RBFOX1, ADARB2, CHD4, and CDH13. The top genes we identified with this method also displayed significant and widespread post hoc effects on voxelwise, tensor-based morphometry (TBM) maps of the temporal lobes. The most significantly associated gene was an autism susceptibility gene known as MACROD2.We were able to successfully replicate the effect of the MACROD2 gene in an independent cohort of 564 young, Australian healthy adult twins and siblings scanned with MRI (mean age: 23.8±2.2 SD years). Our approach powerfully complements univariate techniques in detecting influences of genes on the living brain.

An iterative contractive framework for probe methods: LASSO

We present a new iterative approach called Line Adaptation for the Singular Sources Objective (LASSO) to object or shape reconstruction based on the singular sources method (or probe method) for the reconstruction of scatterers from the far-field pattern of scattered acoustic or electromagnetic waves. The scheme is based on the construction of an indicator function given by the scattered field for incident point sources in its source point from the given far-field patterns for plane waves. The indicator function is then used to drive the contraction of a surface which surrounds the unknown scatterers. A stopping criterion for those parts of the surfaces that touch the unknown scatterers is formulated. A splitting approach for the contracting surfaces is formulated, such that scatterers consisting of several separate components can be reconstructed. Convergence of the scheme is shown, and its feasibility is demonstrated using a numerical study with several examples.

Prediction error property of the Lasso Estimator and its generalization

The lasso procedure is an estimator-shrinkage and variable selection method. This paper shows that there always exists an interval of tuning parameter values such that the corresponding mean squared prediction error for the lasso estimator is smaller than for the ordinary least squares estimator. For an estimator satisfying some condition such as unbiasedness, the paper defines the corresponding generalized lasso estimator. Its mean squared prediction error is shown to be smaller than that of the estimator for values of the tuning parameter in some interval. This implies that all unbiased estimators are not admissible. Simulation results for five models support the theoretical results.

Identifying markov blankets using lasso estimation

Determining the causal relation among attributes in a domain is a key task in data mining and knowledge discovery. The Minimum Message Length (MML) principle has demonstrated its ability in discovering linear causal models from training data. To explore the ways to improve efficiency, this paper proposes a novel Markov Blanket identification algorithm based on the Lasso estimator. For each variable, this algorithm first generates a Lasso tree, which represents a pruned candidate set of possible feature sets. The Minimum Message Length principle is then employed to evaluate all those candidate feature sets, and the feature set with minimum message length is chosen as the Markov Blanket. Our experiment results show the ability of this algorithm. In addition, this algorithm can be used to prune the search space of causal discovery, and further reduce the computational cost of those score-based causal discovery algorithms.

Stable feature selection for clinical prediction: Exploiting ICD tree structure using Tree-Lasso

Modern healthcare is getting reshaped by growing Electronic Medical Records (EMR). Recently, these records have been shown of great value towards building clinical prediction models. In EMR data, patients' diseases and hospital interventions are captured through a set of diagnoses and procedures codes. These codes are usually represented in a tree form (e.g. ICD-10 tree) and the codes within a tree branch may be highly correlated. These codes can be used as features to build a prediction model and an appropriate feature selection can inform a clinician about important risk factors for a disease. Traditional feature selection methods (e.g. Information Gain, T-test, etc.) consider each variable independently and usually end up having a long feature list. Recently, Lasso and related l1-penalty based feature selection methods have become popular due to their joint feature selection property. However, Lasso is known to have problems of selecting one feature of many correlated features randomly. This hinders the clinicians to arrive at a stable feature set, which is crucial for clinical decision making process. In this paper, we solve this problem by using a recently proposed Tree-Lasso model. Since, the stability behavior of Tree-Lasso is not well understood, we study the stability behavior of Tree-Lasso and compare it with other feature selection methods. Using a synthetic and two real-world datasets (Cancer and Acute Myocardial Infarction), we show that Tree-Lasso based feature selection is significantly more stable than Lasso and comparable to other methods e.g. Information Gain, ReliefF and T-test. We further show that, using different types of classifiers such as logistic regression, naive Bayes, support vector machines, decision trees and Random Forest, the classification performance of Tree-Lasso is comparable to Lasso and better than other methods. Our result has implications in identifying stable risk factors for many healthcare problems and therefore can potentially assist clinical decision making for accurate medical prognosis.

Classification and selection of biomarkers in genomic data using LASSO

High-throughput gene expression technologies such as microarrays have been utilized in a variety of scientific applications. Most of the work has been on assessing univariate associations between gene expression with clinical outcome (variable selection) or on developing classification procedures with gene expression data (supervised learning). We consider a hybrid variable selection/classification approach that is based on linear combinations of the gene expression profiles that maximize an accuracy measure summarized using the receiver operating characteristic curve. Under a specific probability model, this leads to consideration of linear discriminant functions. We incorporate an automated variable selection approach using LASSO. An equivalence between LASSO estimation with support vector machines allows for model fitting using standard software. We apply the proposed method to simulated data as well as data from a recently published prostate cancer study.

Orlando di Lasso, Brustbild

Signatur des Originals: S 36/F01064

Orlando di Lasso, Brustbild

Signatur des Originals: S 36/F01065

Orlando di Lasso, Denkmal

Signatur des Originals: S 36/F05137

Orlando di Lasso, Brustbild

Signatur des Originals: S 36/G00084

Orlando di Lasso, Brustbild

Signatur des Originals: S 36/G00087

Orlando di Lasso, Brustbild

Signatur des Originals: S 36/G00088

Orlando di Lasso, Brustbild

Signatur des Originals: S 36/G01376

Orlando di Lasso, Brustbild

Signatur des Originals: S 36/G03275