Inferential stability in systems biology

The modern biological sciences are fraught with statistical difficulties. Biomolecular stochasticity, experimental noise, and the “large p, small n” problem all contribute to the challenge of data analysis. Nevertheless, we routinely seek to draw robust, meaningful conclusions from observations. In this thesis, we explore methods for assessing the effects of data variability upon downstream inference, in an attempt to quantify and promote the stability of the inferences we make. We start with a review of existing methods for addressing this problem, focusing upon the bootstrap and similar methods. The key requirement for all such approaches is a statistical model that approximates the data generating process. We move on to consider biomarker discovery problems. We present a novel algorithm for proposing putative biomarkers on the strength of both their predictive ability and the stability with which they are selected. In a simulation study, we find our approach to perform favourably in comparison to strategies that select on the basis of predictive performance alone. We then consider the real problem of identifying protein peak biomarkers for HAM/TSP, an inflammatory condition of the central nervous system caused by HTLV-1 infection. We apply our algorithm to a set of SELDI mass spectral data, and identify a number of putative biomarkers. Additional experimental work, together with known results from the literature, provides corroborating evidence for the validity of these putative biomarkers. Having focused on static observations, we then make the natural progression to time course data sets. We propose a (Bayesian) bootstrap approach for such data, and then apply our method in the context of gene network inference and the estimation of parameters in ordinary differential equation models. We find that the inferred gene networks are relatively unstable, and demonstrate the importance of finding distributions of ODE parameter estimates, rather than single point estimates

Proxy Assertion

In proxy assertion an individual or group asserts something through a spokesperson. The chapter explains proxy assertion as resting on the assignment of a status role to a person (that of spokesperson) whose utterances acts in virtue of that role have the status function of signaling that the principal is committed in a way analogous to an individual asserting that in his own voice. The chapter briefly explains how status functions and status roles are grounded and then treats, in turn, the case of a spokesperson for an individual and a group and the differences in the significance of what the spokesperson does in each case. Finally, it reviews complications introduced by spokesperson autonomy, where the spokesperson is given leave to represent her principal’s views or positions in her own words and to respond to questions on his behalf

Fission, First Person Thought, and Subject-body Dualism

In “The Argument for Subject Body Dualism from Transtemporal Identity Defended” (PPR 2013), Martine Nida-Rümelin (NR) responded to my (PPR 2013) criticism of her (2010) argument for subject-body dualism. The crucial premise of her (2010) argument was that there is a factual difference between the claims that in a fission case the original person is identical with one, or the other, of the successors. I argued that, on the three most plausible interpretations of ‘factual difference’, the argument fails. NR responds that I missed the intended, fourth interpretation, and that, in any case, with an additional assumption, the argument on the third interpretation goes through. I argue that the fourth interpretation, while insufficient as stated, reveals an assumption that provides an independent argument, namely, that in first person thought about future properties we have a positive conception of the self that rules out having empirical criteria of transtemporal identity. I argue that the considerations offered for this thesis fail to establish it, and that we do not bring ourselves under any positive conception in first person thought. I argue also that on the third interpretation, the first premise of the argument is inconsistent with the necessity of identity

A review of central production experiments at the CERN Omega spectrometer

The non-Abelian nature of QCD suggests that particles that have a gluon constituent, such as glueballs or hybrids, should exist. This paper presents a study of central meson production in the fixed target experiments WA76, WA91 and WA102 at the CERN Omega spectrometer at centre-of-mass energies of $\sqrt{s} = 12.7$, 23.8 and 29~GeV. A study of the resonance production cross section as a function of $\sqrt{s}$ shows which states are compatible with being produced by Double Pomeron Exchange (DPE). In these DPE processes, the difference in the transverse momentum between the exchange particles ($dP_T)$ can be used to select out known $q\overline q$ states from non-$q \overline q$ candidates. The distribution of the azimuthal angle ($\phi$) between the two exchange particles suggests that the Pomeron transforms like a non-conserved vector current. Finally there is evidence from an analysis of the the decay modes of the scalar states observed, that the lightest scalar glueball manifests itself through the mixing with nearby $q\overline q$ states.Comment: 14 pages, 8 figures. arXiv admin note: text overlap with arXiv:hep-ph/000805