Statistics and Probability Commons^™

Probabilistic Modeling Of Personalized Drug Combinations From Integrated Chemical Screen And Molecular Data In Sarcoma, Noah E. Berlow, Rishi Rikhi, Mathew Geltzeiler, Jinu Abraham, Matthew N. Svalina, Lara E. Davis, Erin Wise, Maria Mancini, Jonathan Noujaim, Atiya Mansoor, Michael J. Quist, Kevin L. Matlock, Martin W. Goros, Brian S. Hernandez, Yee C. Doung, Khin Thway, Tomohide Tsukahara, Jun Nishio, Elaine T. Huang, Susan Airhart, Carol J. Bult, Regina Gandour-Edwards, Robert G. Maki, Robin L. Jones, Joel E. Michalek, Milan Milovancev, Souparno Ghosh, Ranadip Pal, Charles Keller

Department of Statistics: Faculty Publications

Background: Cancer patients with advanced disease routinely exhaust available clinical regimens and lack actionable genomic medicine results, leaving a large patient population without effective treatments options when their disease inevitably progresses. To address the unmet clinical need for evidence-based therapy assignment when standard clinical approaches have failed, we have developed a probabilistic computational modeling approach which integrates molecular sequencing data with functional assay data to develop patient-specific combination cancer treatments. Methods: Tissue taken from a murine model of alveolar rhabdomyosarcoma was used to perform single agent drug screening and DNA/RNA sequencing experiments; results integrated via our computational modeling approach identified …

Informative Group Testing For Multiplex Assays, Christopher R. Bilder, Joshua M. Tebbs, Christopher S. Mcmahan

Department of Statistics: Faculty Publications

Infectious disease testing frequently takes advantage of two tools–group testing and multiplex assays–to make testing timely and cost effective. Until the work of Tebbs et al. (2013) and Hou et al. (2017), there was no research available to understand how best to apply these tools simultaneously. This recent work focused on applications where each individual is considered to be identical in terms of the probability of disease. However, risk-factor information, such as past behavior and presence of symptoms, is very often available on each individual to allow one to estimate individual-specific probabilities. The purpose of our paper is to propose …

Functional Random Forest With Applications In Dose-Response Predictions, Raziur Rahman, Saugato Rahman Dhruba, Souparno Ghosh, Ranadip Pal

Department of Statistics: Faculty Publications

Drug sensitivity prediction for individual tumors is a significant challenge in personalized medicine. Current modeling approaches consider prediction of a single metric of the drug response curve such as AUC or IC₅₀. However, the single summary metric of a dose-response curve fails to provide the entire drug sensitivity profile which can be used to design the optimal dose for a patient. In this article, we assess the problem of predicting the complete dose-response curve based on genetic characterizations. We propose an enhancement to the popular ensemble-based Random Forests approach that can directly predict the entire functional profile of …

Cost-Effective Surveillance For Infectious Diseases Through Specimen Pooling And Multiplex Assays, Christopher Bilder, Joshua Tebbs, Christopher Mcmahan

Department of Statistics: Faculty Publications

To develop specimen pooling algorithms that reduce the number of tests needed to test individuals for infectious diseases with multiplex assays.

Genomic Prediction Using Canopy Coverage Image And Genotypic Information In Soybean Via A Hybrid Model, Reka Howard, Diego Jarquin

Department of Statistics: Faculty Publications

Prediction techniques are important in plant breeding as they provide a tool for selection that is more efficient and economical than traditional phenotypic and pedigree based selection. The conventional genomic prediction models include molecular marker information to predict the phenotype. With the development of new phenomics techniques we have the opportunity to collect image data on the plants, and extend the traditional genomic prediction models where we incorporate diverse set of information collected on the plants. In our research, we developed a hybrid matrix model that incorporates molecular marker and canopy coverage information as a weighted linear combination to predict …

Post-Er Stress Biogenesis Of Golgi Is Governed By Giantin, Cole P. Frisbie, Alexander Y. Lushnikov, Alexey V. Krasnoslobodtsev, Jean-Jack Riethoven, Jennifer L. Clarke, Elena I. Stepchenkova, Armen Petrosyan

Department of Statistics: Faculty Publications

Background: The Golgi apparatus undergoes disorganization in response to stress, but it is able to restore compact and perinuclear structure under recovery. This self-organization mechanism is significant for cellular homeostasis, but remains mostly elusive, as does the role of giantin, the largest Golgi matrix dimeric protein. Methods: In HeLa and different prostate cancer cells, we used the model of cellular stress induced by Brefeldin A (BFA). The conformational structure of giantin was assessed by proximity ligation assay and atomic force microscopy. The post-BFA distribution of Golgi resident enzymes was examined by 3D SIM high-resolution microscopy. Results: We detected that giantin …

Recursive Model For Dose-Time Responses In Pharmacological Studies, Saugato Rahman Dhruba, Aminur Rahman, Raziur Rahman, Souparno Ghosh, Ranadip Pal

Department of Statistics: Faculty Publications

Background: Clinical studies often track dose-response curves of subjects over time. One can easily model the dose-response curve at each time point with Hill equation, but such a model fails to capture the temporal evolution of the curves. On the other hand, one can use Gompertz equation to model the temporal behaviors at each dose without capturing the evolution of time curves across dosage

Results: In this article, we propose a parametric model for dose-time responses that follows Gompertz law in time and Hill equation across dose approximately. We derive a recursion relation for dose-response curves over time capturing the …

An Information Theory-Based Approach To Assessing Spatial Patterns In Complex Systems, Tarsha Eason, Wen Ching-Chuang, Shana Sundstrom, Heriberto Cabezas

School of Natural Resources: Faculty Publications

Given the intensity and frequency of environmental change, the linked and cross-scale nature of social-ecological systems, and the proliferation of big data, methods that can help synthesize complex system behavior over a geographical area are of great value. Fisher information evaluates order in data and has been established as a robust and effective tool for capturing changes in system dynamics, including the detection of regimes and regime shifts. The methods developed to compute Fisher information can accommodate multivariate data of various types and requires no a priori decisions about system drivers, making it a unique and powerful tool. However, the …

Pawnee Dam Inflow Design Flood (Idf) Update And Stage-Frequency Curve Development Using Rmcrfa, Jennifer P. Christensen, Joshua J. Melliger

United States Geological Survey: Water Reports and Publications

Pawnee Dam is one of the ten Salt Creek Dams designed and built in the 1960s to mitigate flooding in Lincoln, Nebraska. This short paper illustrates the update of the Pawnee Dam inflow design flood (IDF) through calibration to recent high flow events and the development of its stage-frequency or hydrologic loading curve with the U.S. Army Corps of Engineers’ Risk Management Center Reservoir Frequency Analysis (RMC-RFA) model. The IDF update follows Engineering Regulation 1110-8-2, Inflow Design Flood for Dams and Reservoirs, including unit hydrograph peaking and two antecedent pool elevations. Background information on the original design of the dam …

Role Of Misclassification Estimates In Estimating Disease Prevalence And A Non-Linear Approach To Study Synchrony Using Heart Rate Variability In Chickens, Dola Pathak

Department of Statistics: Dissertations, Theses, and Student Research

Infectious disease assays can be imperfect. When estimating disease prevalence, these imperfections are accounted for by incorporating assay sensitivity and specificity into point and variance estimates. Unfortunately, these accuracy measures are often treated as fixed constants, rather than acknowledging that they are estimates from an assay validation process. The purpose of this study is to show the detrimental effect of not taking into account this sampling variability when samples are obtained through group testing (aka, pooled testing). We show that confidence interval coverage can dramatically decline as the sample size increases for the main sample of interest. As a remedy …

Statistical Investigation Of Road And Railway Hazardous Materials Transportation Safety, Amirfarrokh Iranitalab

Department of Civil and Environmental Engineering: Dissertations, Theses, and Student Research

Transportation of hazardous materials (hazmat) in the United States (U.S.) constituted 22.8% of the total tonnage transported in 2012 with an estimated value of more than 2.3 billion dollars. As such, hazmat transportation is a significant economic activity in the U.S. However, hazmat transportation exposes people and environment to the infrequent but potentially severe consequences of incidents resulting in hazmat release. Trucks and trains carried 63.7% of the hazmat in the U.S. in 2012 and are the major foci of this dissertation. The main research objectives were 1) identification and quantification of the effects of different factors on occurrence and …

Quantitative Appraisal Of Non-Irrigated Cropland In South Dakota, Shelby Riggs

Honors Program: Senior Projects (Public)

This appraisal attempts to remove subjectivity from the appraisal process and replace it with quantitative analysis of known data to generate a fair market value of the subject property. Two methods of appraisal were used, the income approach and the comparable sales approach. For the income approach, I used the average cash rent for the region, the current property taxes for the subject property, and a capitalization rate based on Stokes' (2018) capitalization rate formula to arrive at my income-based valuation. For the comparable sales approach, I utilized Stokes' (2018) research in optimization modeling to estimate a market value for …

Essentials Of Structural Equation Modeling, Mustafa Emre Civelek

Zea E-Books Collection

Structural Equation Modeling is a statistical method increasingly used in scientific studies in the fields of Social Sciences. It is currently a preferred analysis method, especially in doctoral dissertations and academic researches. However, since many universities do not include this method in the curriculum of undergraduate and graduate courses, students and scholars try to solve the problems they encounter by using various books and internet resources.

This book aims to guide the researcher who wants to use this method in a way that is free from math expressions. It teaches the steps of a research program using structured equality modeling …

Existing And Potential Statistical And Computational Approaches For The Analysis Of 3d Ct Images Of Plant Roots, Zheng Xu, Camilo Valdes, Jennifer Clarke

Department of Statistics: Faculty Publications

Scanning technologies based on X-ray Computed Tomography (CT) have been widely used in many scientific fields including medicine, nanosciences and materials research. Considerable progress in recent years has been made in agronomic and plant science research thanks to X-ray CT technology. X-ray CT image-based phenotyping methods enable high-throughput and non-destructive measuring and inference of root systems, which makes downstream studies of complex mechanisms of plants during growth feasible. An impressive amount of plant CT scanning data has been collected, but how to analyze these data efficiently and accurately remains a challenge. We review statistical and computational approaches that have been …

Characterization Of Soybean Protein Adhesives Modified By Xanthan Gum, Chen Feng, Fang Wang, Zheng Xu, Huilin Sui, Yong Fang, Xiaozhi Tang, Xinchun Shen

Department of Statistics: Faculty Publications

The aim of this study was to provide a basis for the preparation of medical adhesives from soybean protein sources. Soybean protein (SP) adhesives mixed with different concentrations of xanthan gum (XG) were prepared. Their adhesive features were evaluated by physicochemical parameters and an in vitro bone adhesion assay. The results showed that the maximal adhesion strength was achieved in 5% SP adhesive with 0.5% XG addition, which was 2.6-fold higher than the SP alone. The addition of XG significantly increased the hydrogen bond and viscosity, as well as increased the β-sheet content but decreased the α-helix content in the …

Development Of 11-Plex Mol-Pcr Assay For The Rapid Screening Of Samples For Shiga Toxin-Producing Escherichia Coli, Travis A. Woods, Heather M. Mendez, Sandy Ortega, Xiaorong Shi, David Marx, Jianfa Bai, Rodney A. Moxley, T. G. Nagaraja, Steven W. Graves, Alina Deshpande

Department of Statistics: Faculty Publications

Strains of Shiga toxin-producing Escherichia coli (STEC) are a serious threat to the health, with approximately half of the STEC related food-borne illnesses attributable to contaminated beef. We developed an assay that was able to screen samples for several important STEC associated serogroups (O26, O45, O103, O104, O111, O121, O145, O157) and three major virulence factors (eae, stx1, stx2) in a rapid and multiplexed format using the Multiplex oligonucleotide ligation-PCR (MOL-PCR) assay chemistry. This assay detected unique STEC DNA signatures and is meant to be used on samples from various sources related to beef production, providing a multiplex and high-throughput …

Application Of Transfer Learning For Cancer Drug Sensitivity Prediction, Saugato Rahman Dhruba, Raziur Rahman, Kevin Matlock, Souparno Ghosh, Ranadip Pal

Department of Statistics: Faculty Publications

Background: In precision medicine, scarcity of suitable biological data often hinders the design of an appropriate predictive model. In this regard, large scale pharmacogenomics studies, like CCLE and GDSC hold the promise to mitigate the issue. However, one cannot directly employ data from multiple sources together due to the existing distribution shift in data. One way to solve this problem is to utilize the transfer learning methodologies tailored to fit in this specific context.

Results: In this paper, we present two novel approaches for incorporating information from a secondary database for improving the prediction in a target database. The first …

Investigation Of Model Stacking For Drug Sensitivity Prediction, Kevin Matlock, Carlos De Niz, Raziur Rahman, Souparno Ghosh, Ranadip Pal

Department of Statistics: Faculty Publications

Background: A significant problem in precision medicine is the prediction of drug sensitivity for individual cancer cell lines. Predictive models such as Random Forests have shown promising performance while predicting from individual genomic features such as gene expressions. However, accessibility of various other forms of data types including information on multiple tested drugs necessitates the examination of designing predictive models incorporating the various data types.

Results: We explore the predictive performance of model stacking and the effect of stacking on the predictive bias and squarred error. In addition we discuss the analytical underpinnings supporting the advantages of stacking in reducing …

The Impact Of Truncating Data On The Predictive Ability For Single-Step Genomic Best Linear Unbiased Prediction, Jeremy T. Howard, Thomas A. Rathje, Caitlyn E. Bruns, Danielle F. Wilson-Wells, Stephen D. Kachman, Matthew L. Spangler

Department of Animal Science: Faculty Publications

Simulated and swine industry data sets were utilized to assess the impact of removing older data on the predictive ability of selection candidate estimated breeding values (EBV) when using single-step genomic best linear unbiased prediction (ssGBLUP). Simulated data included thirty replicates designed to mimic the structure of swine data sets. For the simulated data, varying amounts of data were truncated based on the number of ancestral generations back from the selection candidates. The swine data sets consisted of phenotypic and genotypic records for three traits across two breeds on animals born from 2003 to 2017. Phenotypes and genotypes were iteratively …

Stat 380: Statistics And Applications, Yumou Qiu

UNL Faculty Course Portfolios

This portfolio prepares for the introduction level undergraduate statistic course (Stat 380) for the students with calculus background, which includes the course goals, contents as well as teaching methods for large session classes. Analysis and evaluation of student learning are also included. In-class activities and discussion helping students’ engagement are introduced. The homework is assigned by Canvas, which summaries the students’ solution and provides analysis for each student.

Heterogeneity Aware Random Forest For Drug Sensitivity Prediction, Raziur Rahman, Kevin Matlock, Souparno Ghosh, Ranadip Pal

Department of Statistics: Faculty Publications

Samples collected in pharmacogenomics databases typically belong to various cancer types. For designing a drug sensitivity predictive model from such a database, a natural question arises whether a model trained on diverse inter-tumor heterogeneous samples will perform similar to a predictive model that takes into consideration the heterogeneity of the samples in model training and prediction. We explore this hypothesis and observe that ensemble model predictions obtained when cancer type is known out-perform predictions when that information is withheld even when the samples sizes for the former is considerably lower than the combined sample size. To incorporate the heterogeneity idea …

A Characterization Of A Value Added Model And A New Multi-Stage Model For Estimating Teacher Effects Within Small School Systems, Julie M. Garai

Department of Statistics: Dissertations, Theses, and Student Research

At both the national and state level there is increasing pressure to develop metrics to determine if school systems are meeting educational objectives. All states mandate some form of assessment by standardized tests. One method currently used to model student test scores is Value Added Modeling (VAM), which models student scores as a product of classroom and school environments. One VAM approach is the Tennessee Value Added Assessment System (TVAAS) which models student gains from year to year. Teacher effects are included in this layered model, which estimates the teacher’s added value to a student score through best linear unbiased …

Testing The Independence Hypothesis Of Accepted Mutations For Pairs Of Adjacent Amino Acids In Protein Sequences, Jyotsna Ramanan, Peter Revesz

School of Computing: Faculty Publications

Evolutionary studies usually assume that the genetic mutations are independent of each other. However, that does not imply that the observed mutations are independent of each other because it is possible that when a nucleotide is mutated, then it may be biologically beneficial if an adjacent nucleotide mutates too. With a number of decoded genes currently available in various genome libraries and online databases, it is now possible to have a large-scale computer-based study to test whether the independence assumption holds for pairs of adjacent amino acids. Hence the independence question also arises for pairs of adjacent amino acids within …

Assessing The Impact Of Retreat Mechanisms In A Simple Antarctic Ice Sheet Model Using Bayesian Calibration, Kelsey L. Ruckert, Gary Shaffer, David Pollard, Yawen Guan, Tony E. Wong, Chris E. Forest, Klaus Keller

Department of Statistics: Faculty Publications

The response of the Antarctic ice sheet (AIS) to changing climate forcings is an important driver of sea-level changes. Anthropogenic climate change may drive a sizeable AIS tipping point response with subsequent increases in coastal flooding risks. Many studies analyzing flood risks use simple models to project the future responses of AIS and its sea-level contributions. These analyses have provided important new insights, but they are often silent on the effects of potentially important processes such as Marine Ice Sheet Instability (MISI) or Marine Ice Cliff Instability (MICI). These approximations can be well justified and result in more parsimonious and …

Perennial Warm-Season Grasses For Producing Biofuel And Enhancing Soil Properties: An Alternative To Corn Residue Removal, Humberto Blanco-Canqui, Robert B. Mitchell, Virginia L. Jin, Marty R. Schmer, Kent M. Eskridge

Department of Statistics: Faculty Publications

Removal of corn (Zea mays L.) residues at high rates for biofuel and other off-farm uses may negatively impact soil and the environment in the long term. Biomass removal from perennial warm-season grasses (WSGs) grown in marginally-productive lands could be an alternative to corn residue removal as biofuel feedstocks while controlling water and wind erosion, sequestering carbon (C), cycling water and nutrients, and enhancing other soil ecosystem services. We compared wind and water erosion potential, soil compaction, soil hydraulic properties, soil organic C (SOC), and soil fertility between biomass removal from WSGs and corn residue removal from rainfed no-till …

Impact Of Menthol Smoking On Nicotine Dependence For Diverse Racial/Ethnic Groups Of Daily Smokers, Julia N. Soulakova, Ryan R. Danczak

Department of Statistics: Faculty Publications

Introduction: The aims of this study were to evaluate whether menthol smoking and race/ethnicity are associated with nicotine dependence in daily smokers. Methods: The study used two subsamples of U.S. daily smokers who responded to the 2010–2011 Tobacco Use Supplement to the Current Population Survey. The larger subsample consisted of 18,849 non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic (HISP) smokers. The smaller subsample consisted of 1112 non-Hispanic American Indian/Alaska Native (AIAN), non-Hispanic Asian (ASIAN), non-Hispanic Hawaiian/Pacific Islander (HPI), and non-Hispanic Multiracial (MULT) smokers. Results: For larger (smaller) groups the rates were 45% (33%) for heavy smoking (16+ cig/day), 59% …

Evaluating Current Practices In Shelf Life Estimation, Robert Capen, David Christopher, Patrick Forenzo, Kim Huynh-Ba, David Leblond, Oscar Liu, John O'Neill, Nate Patterson, Michelle Quinlan, Radhika Rajagopalan, James Schwenke, Walter W. Stroup

Department of Statistics: Faculty Publications

The current International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) methods for determining the supported shelf life of a drug product, described in ICH guidance documents Q1A and Q1E, are evaluated in this paper. To support this evaluation, an industry data set is used which is comprised of 26 individual stability batches of a common drug product where most batches are measured over a 24 month storage period. Using randomly sampled sets of 3 or 6 batches from the industry data set, the current ICH methods are assessed from three perspectives. First, the distributional properties …

Generalized Confidence Intervals Compatible With The Min Test For Simultaneous Comparisons Of One Subpopulation To Several Other Subpopulations, Julia N. Soulakova

Department of Statistics: Faculty Publications

A problem where one subpopulation is compared to several other subpopulations in terms of means with the goal of estimating the smallest difference between the means commonly arises in biology, medicine, and many other scientific fields. A generalization of Strassburger, Bretz and Hochberg (2004) approach for two comparisons is presented for cases with three and more comparisons. The method allows constructing an interval-estimator for the smallest mean difference, which is compatible with the Min test. An application to a fluency-disorder study is illustrated. Simulations confirmed adequate probability coverage for normally distributed outcomes for a number of designs.

Increasing Genomic-Enabled Prediction Accuracy By Modeling Genotype X Environment Interactions In Kansas Wheat, Diego Jarquin, Cristiano Lemas Da Silva, R. Chris Gaynor, Jesse Poland, Allan Fritz, Reka Howard, Sarah Battenfield, José Crossa

Department of Statistics: Faculty Publications

Wheat (Triticum aestivum L.) breeding programs test experimental lines in multiple locations over multiple years to get an accurate assessment of grain yield and yield stability. Selections in early generations of the breeding pipeline are based on information from only one or few locations and thus materials are advanced with little knowledge of the genotype × environment interaction (G × E) effects. Later, large trials are conducted in several locations to assess the performance of more advanced lines across environments. Genomic selection (GS) models that include G × E covariates allow us to borrow information not only from related …

Application Of Response Surface Methods To Determine Conditions For Optimal Genomic Prediction, Reka Howard, Alicia L. Carriquiry, William D. Beavis

Department of Statistics: Faculty Publications

An epistatic genetic architecture can have a significant impact on prediction accuracies of genomic prediction (GP) methods. Machine learning methods predict traits comprised of epistatic genetic architectures more accurately than statistical methods based on additive mixed linear models. The differences between these types of GP methods suggest a diagnostic for revealing genetic architectures underlying traits of interest. In addition to genetic architecture, the performance of GP methods may be influenced by the sample size of the training population, the number of QTL, and the proportion of phenotypic variability due to genotypic variability (heritability). Possible values for these factors and the …