arXiv subjects

Nicholas D. Socci

Publications and source records attributed to Nicholas D. Socci.

6 recordsLinked to original sources

arXiv2013

Comprehensive evaluation of differential expression analysis methods for RNA-seq data

High-throughput sequencing of RNA transcripts (RNA-seq) has become the method of choice for detection of differential expression (DE). Concurrent with the growing popularity of this technology there has been a significant research effort devoted towards understanding the statistical properties of this data and the development of analysis methods. We report on a comprehensive evaluation of the commonly used DE methods using the SEQC benchmark data set. We evaluate a number of key features including: assessment of normalization, accuracy of DE detection, modeling of genes expressed in only one condition, and the impact of sequencing depth and number of replications on identifying DE genes. We find significant differences among the methods with no single method consistently outperforming the others. Furthermore, the performance of array-based approach is comparable to methods customized for RNA-seq data. Perhaps most importantly, our results demonstrate that increasing the number of replicate samples provides significantly more detection power than increased sequencing depth.

q-bio.GN↗

arXiv2005

Non-equilibrium raft-like membrane domains under continuous recycling

We present a model for the kinetics of spontaneous membrane domain (raft) assembly that includes the effect of membrane recycling ubiquitous in living cells. We show that the domains have a broad power-law distribution with an average radius that scales with the 1/4 power of the domain lifetime when the line tension at the domain edges is large. For biologically reasonable recycling and diffusion rates the average domain radius is in the tens of nm range, consistent with observations. This represents one possible link between signaling (involving rafts) and traffic (recycling) in cells. Finally, we present evidence that suggests that the average raft size may be the same for all scale-free recycling schemes.

cond-mat.soft↗

arXiv2002

A study of accuracy and precision in oligonucleotide arrays: extracting more signal at large concentrations

Despite the success and popularity of oligonucleotide arrays as a high-throughput technique for measuring mRNA expression levels, quantitative calibration studies have until now been limited. The main reason is that suitable data was not available. However, calibration data recently produced by Affymetrix now permits detailed studies of the intensity dependent sensitivity. Given a certain transcript concentration, it is of particular interest to know whether current analysis methods are capable of detecting differential expression ratios of 2 or higher. Using the calibration data, we demonstrate that while current techniques are capable of detecting changes in the low to mid concentration range, the situation is noticeably worse for high concentrations. In this regime, expression changes as large as 4 fold are severely biased, and changes of 2 are often undetectable. Such effects are mainly the consequence of the sequence specific binding properties of probes, and not the result of optical saturation in the fluorescence measurements. GeneChips are manufactured such that each transcript is probed by a set of sequences with a wide affinity range. We show that this property can be used to design a method capable of reducing the high intensity bias. The idea behind our methods is to transfers the weight of a measurement to a subset of probes with optimal linear response at a given concentration, which can be achieved using local embedding techniques.

physics.bio-ph↗

arXiv1995

Kinetic and thermodynamic analysis of proteinlike heteropolymers: Monte Carlo histogram technique

Using Monte Carlo dynamics and the Monte Carlo Histogram Method, the simple three-dimensional 27 monomer lattice copolymer is examined in depth. The thermodynamic properties of various sequences are examined contrasting the behavior of good and poor folding sequences. The good (fast folding) sequences have sharp well-defined thermodynamic transitions while the slow folding sequences have broad ones. We find two independent transitions: a collapse transition to compact states and a folding transition from compact states to the native state. The collapse transition is second order-like, while folding is first order. The system is also studied as a function of the energy parameters. In particular, as the average energetic drive toward compactness is reduced, the two transitions approach each other. At zero average drive, collapse and folding occur almost simultaneously; i.e., the chain collapses directly into the native state. At a specific value of this energy drive the folding temperature falls below the glass point, indicating that the chain is now trapped in local minimum. By varying one parameter in this simple model, we obtain a diverse array of behaviors which may be useful in understanding the different folding properties of various proteins.

chem-ph↗

arXiv1994

Folding Kinetics of Protein Like Heteropolymers

Using a simple three-dimensional lattice copolymer model and Monte Carlo dynamics, we study the collapse and folding of protein-like heteropolymers. The polymers are 27 monomers long and consist of two monomer types. Although these chains are too long for exhaustive enumeration of all conformations, it is possible to enumerate all the maximally compact conformations, which are 3x3x3 cubes. This allows us to select sequences that have a unique global minimum. We then explore the kinetics of collapse and folding and examine what features determine the various rates. The folding time has a plateau over a broad range of temperatures and diverges at both high and low temperatures. The folding time depends on sequence and is related to the amount of energetic frustration in the native state. The collapse times of the chains are sequence independent and are a few orders of magnitude faster than the folding times, indicating a two-phase folding process. Below a certain temperature the chains exhibit glass-like behavior, characterized by a slowing down of time scales and loss of self-averaging behavior. We explicitly define the glass transition temperature (Tg), and by comparing it to the folding temperature (Tf), we find two classes of sequences: good folders with Tf > Tg and non-folders with Tf < Tg.

cond-mat↗

arXiv1994

Properties and Origins of Protein Secondary Structure

Proteins contain a large fraction of regular, repeating conformations, called secondary structure. A simple, generic definition of secondary structure is presented which consists of measuring local correlations along the protein chain. Using this definition and a simple model for proteins, the forces driving the formation of secondary structure are explored. The relative role of energy and entropy are examined. Recent work has indicated that compaction is sufficient to create secondary structure. We test this hypothesis, using simple non-lattice protein models.

cond-mat↗