IMPROVED METHODS FOR THE ANALYSIS OF SINGLE-CELL RNA-SEQUENCING AND IMAGING DATA

Two key challenges in the analysis of single cell RNA-seq (scRNA-seq) data are excess zeros due to “drop-out” events and substantial overdispersion due to stochastic and systematic differences. Association analysis of scRNA-seq data is further confronted with the possible dependency introduced by measuring multiple single cells from the same biological sample. To address these three challenges, the first chapter of this work proposes TWO-SIGMA: a TWO-component SInGle cell Model-based Association method for differential expression analysis of scRNA-seq data. The first component models the drop-out probability with a mixed-effects logistic regression, and the second component models the (conditional) mean read count with a mixed-effects negative binomial regression. Simulation studies and real data analysis show advantages in type-I error control and power enhancement over alternative approaches including MAST and a zero-inflated negative binomial model without random effects. The second chapter of this dissertation expands the first to Gene set testing (GST). Here, we propose TWO-SIGMA-Geneset to conduct competitive gene set testing, in which the genes in a given set are compared to the remaining collection of genes. Previous work has demonstrated that inter-gene correlation can substantially inflate type-I error. We provide an adjustment for inter-gene correlation, which is estimated using the residuals from the gene-level TWO-SIGMA model. Simulation studies show that type-I error is well controlled in a variety of representative scenarios, with or without inter-gene correlation present. Power is improved over state-of-the-art methods, including CAMERA, for a variety of scenarios consistent with real single-cell RNA-seq data. Finally, the third chapter of this work studies chromosomal interactions at the single-cell level. First, we discuss the Hi-C technology for analyzing genome-wide chromosomal interactions. In particular, we focus on peak calling, in which the aim is to separate interactions between loci that are due to random chance from interactions that are not random. Second, we discuss state-of-the-art methods for single-cell imaging. We then show an example of a way to combine information from Hi-C and imaging data from Drosophilia embryos for peak calling using the Cauchy Combination Test. We conclude by discussing potential future research in this context.Doctor of Philosoph

To see or not to see a Bow Shock: Identifying Bow Shocks with H-Alpha Allsky Surveys

OB-stars have the highest luminosities and strongest stellar winds of all stars, which enables them to interact strongly with their surrounding ISM, thus creating bow shocks. These offer us an ideal opportunity to learn more about the ISM. They were first detected and analysed around runaway OB-stars using the IRAS allsky survey by van Buren et al. (1995). Using the geometry of such bow shocks information concerning the ISM density and its fluctuations can be gained from such infrared observations. As to help to improve the bow shock models, additional observations at other wavelengths, e.g. H-Alpha, are most welcome. However due to their low velocity these bow shocks have a size of ~1 degrees, and could only be observed as a whole with great difficulties. In the light of the new H-Alpha allsky surveys (SHASSA/VTSS) this is no problem any more. We developed different methods to detect bow shocks, e.g. the improved determination of their symmetry axis with radial distance profiles. Using two H-Alpha-allsky surveys (SHASSA/VTSS), we searched for bow shocks and compared the different methods. From our sample we conclude, that the correlation between the direction of both proper motion and the symmetry axis determined with radial distance profile is the most promising detection method. We found eight bow shocks around HD 17505, HD 24430, HD 48099, HD 57061, HD 92206, HD 135240, HD 149757, and HD 158186 from 37 candidates taken from van Buren et al. (1995). Additionally to the traditional determination of ISM parameters using the standoff distance of the bow shock, another approach was chosen, using the thickness of the bow-shock layer. Both methods lead to the same results, yielding densities (~1 cm^{-3}) and the maximal temperatures (~10^4 K), that fit well to the up-to-date picture of the Warm Ionised Medium.Comment: 12 pages, 12 figures, Accepted, A&A 04/28/200

Traces of Thermalization from Transverse Momentum Fluctuations in Nuclear Collisions

Scattering of particles produced in Au+Au collisions at RHIC can wrestle the system into a state near local thermal equilibrium. I illustrate how measurements of the centrality dependence of the mean transverse momentum and its fluctuations can exhibit this thermalization.Comment: 4 pages, 2 eps figures, final version to appear in PR

A Candidate Protoplanet in the Taurus Star Forming Region

HST/NICMOS images of the class I protostar TMR-1 (IRAS04361+2547) reveal a faint companion with 10.0" = 1400 AU projected separation. The central protostar is itself resolved as a close binary with 0.31" = 42 AU separation, surrounded by circumstellar reflection nebulosity. A long narrow filament seems to connect the protobinary to the faint companion TMR-1C, suggesting a physical association. If the sources are physically related then we hypothesize that TMR-1C has been ejected by the protobinary. If TMR-1C has the same age and distance as the protobinary then current models indicate its flux is consistent with a young giant planet of several Jovian masses.Comment: 16 pages, 1 figure, Accepted by Astrophysical Journal Letters, Related information is available at http://www.extrasolar.co

Comparison of Visual Analog Pain Score Reported to Physician vs Nurse in Nonoperatively Treated Foot and Ankle Patients

Background: Patient reported outcome measures (PROMs) are taking a more prominent role in Orthopedics as health care seeks to define treatment outcomes. The Visual Analogue Scale (VAS) is considered a reliable measure of acute pain. A previous study found that operative candidates’ VAS pain score was significantly higher when reported to the surgeon compared to the nurse. This study’s aim is to examine whether this phenomenon occurs in nonoperative patients. We hypothesize that patients’ VAS scores reported to the surgeon and a nurse will be the same Methods: This study is a retrospective cohort of 201 consecutive nonoperative patients treated by a single surgeon. Patients were asked to rate pain intensity by a nurse followed by the surgeon using a horizontal VAS, 0 “no pain” to 10 worst pain”. Differences in reported pain levels were compared with data from the previous cohort of 201 consecutive operative patients. Results: The mean VAS score reported to the nurse was 3.2 whereas the mean VAS score reported to the surgeon was 4.2 (p\u3c.001). The mean difference in VAS scores reported for operative patients was 2.9, whereas the mean difference for nonoperative patients was 1.0 (p \u3c .001). Conclusion: This study found statistically significant differences between VAS scores reported to the surgeon versus the nurse in nonoperative patients which support the trend found in our previous study, where operative patients reported significantly higher scores to the surgeon. The mean difference between reported pain scores is significantly higher for operative patients compared to nonoperative patients

Case-Control Study of Risk Factors Associated with Feline and Canine Chronic Kidney Disease

An age-matched case-control study was initiated to determine the major risk factors associated with CKD in cats and dogs and to determine what clinical signs cat and dog owners observed before their veterinarian diagnosed their pet with CKD. When compared to controls, the feline cases were more likely to have had polydipsia and polyuria in the year before the owners' cats were diagnosed with CKD. In the dogs, increased water intake, increased urination, small size and a recent history of weight loss and bad breath were noticed by the dog owners before veterinary CKD diagnosis. Dog owners recognized abnormal drinking and urination behavior over half a year before their pet's veterinary diagnosis with CKD, and they recognized weight loss almost 4 months before CKD diagnosis. Bad breath was noticed 1.2 years before recognition of CKD by a veterinarian. Given that earlier CKD diagnosis should have been possible in most cases, clinical trials should proceed to measure the efficacy of early interventions

Development and test of an IR camera for astronomical observation at the Palomar 200-inch observatory using the NICMOS II array

A NICMOS II array, a NIR (0.80 - 2.6 micron) imaging system, was integrated into the California Institute of Technology Palomar Observatory camera. The Palomar camera system which consists of six discrete subsystems including a focal plane, an electrical interface, data acquisition electronics, a dewar, dewar optics, and the software is described. The performance and calibration data for each subsystem are presented. Emphasis is placed on test data on the focal plane performance

An IR Search for Extinguished Supernovae in Starburst Galaxies

IR and Radio band observations of heavily extinguished regions in starburst galaxies suggest a very high SN rate associated with such regions. Optically measured supernova (SN) rates may therefore underestimate the total SN rate by factors of up to 10, due to the high extinction to SNe in starburst regions. The IR/radio SN rates come from a variety of indirect means, however, which suffer from model dependence and other problems. We describe a direct measurement of the SN rate from a regular patrol of starburst galaxies done with K' band imaging to minimize the effects of extinction. A collection of K' measurements of core-collapse SNe near maximum light is presented. Results of a preliminary SN search using the MIRC camera at the Wyoming IR Observatory (WIRO), and an improved search using the ORCA optics are described. A monthly patrol of starburst galaxies within 25 Mpc should yield 1.6 - 9.6 SNe/year. Our MIRC search with low-resolution (2.2" pixels) failed to find extinguished SNe, limiting the SN rate outside the nucleus (at > 15" radius) to less than 3.8 Supernova Rate Units (SRU or SNe/century/10^10 L(solar); 90% confidence). The MIRC camera had insufficient resolution to search nuclear starburst regions, where SN activity is concentrated, explaining why we found no heavily obscured SNe. We conclude that high-resolution, small field SN searches in starburst nuclei are more productive than low resolution, large-field searches, even for our large galaxies. With our ORCA high-resolution optics, we could limit the total SN rate to < 1.3 SRU at 90% confidence in 3 years of observations, lower than the most pessimistic estimate.Comment: AJ Submitted 1998 Dec. 13. View figures and download all as one file at http://panisse.lbl.gov/public/bruce/irs