MOTIVATION: The interactions between microbial colonies through chemical signaling are not well understood. A microbial colony can use different molecules to inhibit or accelerate the growth of other colonies. A better understanding of the molecules involved in these interactions could lead to advancements in health and medicine. Imaging mass spectrometry (IMS) applied to co-cultured microbial communities aims to capture the spatial characteristics of the colonies' molecular fingerprints. These data are high-dimensional and require computational analysis methods to interpret. RESULTS: Here, we present a dictionary learning method that deconvolves spectra of different molecules from IMS data. We call this method MOLecular Dictionary Learning ( MOLDL: ). Unlike standard dictionary learning methods which assume Gaussian-distributed data, our method uses the Poisson distribution to capture the count nature of the mass spectrometry data. Also, our method incorporates universally applicable information on common ion types of molecules in MALDI mass spectrometry. This greatly reduces model parameterization and increases deconvolution accuracy by eliminating spurious solutions. Moreover, our method leverages the spatial nature of IMS data by assuming that nearby locations share similar abundances, thus avoiding overfitting to noise. Tests on simulated datasets show that this method has good performance in recovering molecule dictionaries. We also tested our method on real data measured on a microbial community composed of two species. We confirmed through follow-up validation experiments that our method recovered true and complete signatures of molecules. These results indicate that our method can discover molecules in IMS data reliably, and hence can help advance the study of interaction of microbial colonies. AVAILABILITY AND IMPLEMENTATION: The code used in this paper is available at: https://github.com/frizfealer/IMS_project.

We propose a multi-view depthmap estimation approach aimed at adaptively ascertaining the pixel level data associations between a reference image and all the elements of a source image set. Namely, we address the question, what aggregation subset of the source image set should we use to estimate the depth of a particular pixel in the reference image? We pose the problem within a probabilistic framework that jointly models pixel-level view selection and depthmap estimation given the local pairwise image photoconsistency. The corresponding graphical model is solved by EM-based view selection probability inference and PatchMatch-like depth sampling and propagation. Experimental results on standard multi-view benchmarks convey the state-of-the art estimation accuracy afforded by mitigating spurious pixel level data associations. Additionally, experiments on large Internet crowd sourced data demonstrate the robustness of our approach against unstructured and heterogeneous image capture characteristics. Moreover, the linear computational and storage requirements of our formulation, as well as its inherent parallelism, enables an efficient and scalable GPU-based implementation.

Recent studies [1] -- [5] have suggested using constraints in the form of relative distance comparisons to represent domain knowledge: d(a, b)

In our paper “Coping with Viral Diversity in HIV Vaccine Design” [1], we presented several approaches to incorporate viral variability within vaccine immunogens, including judicious choice of natural strains. Most of our approaches included at least one collinear gene length corresponding to the Center-of-Tree (COT) sequence, which has near-optimal peptide coverage for a single gene. Inclusion of a COT sequence and optimizing the rest of the immunogen for coverage, as suggested in [2], yielded a construct (COT+) with the greatest coverage of peptide diversity, minimally sacrificing peptide coverage in comparison with unconstrained diversity optimization. Fischer et al. [3] introduced mosaics—a different approach to increasing coverage while maintaining collinearity using an optimization algorithm based on simulated recombination. In their response to Nickle et al. [1], Fischer et al. [4] suggest that maintaining full collinearity of viral gene sequences with native viral proteins is the only tractable approach to producing immunogens inclusive of viral variability. This claim was based on the observation that mosaics had slightly higher coverage than COT+ at 3× and 4× strain lengths, despite the fact that all mosaic components are constrained to be collinear with the full gene. However, as we pointed out, a variety of optimization algorithms can be used to perform coverage optimization, with computationally intensive approaches typically yielding better results. Figure 1 compares the coverage of mosaics with COT+ constructs produced by two optimization algorithms—the simple greedy extension described in Nickle et al. [1], which can be implemented in hours and run in seconds on any modern personal computer, and the more complex combinatiorial optimization approach of [5] run for one day on a cluster of 300 PCs. We also include the coverage of a construct optimized without any collinearity constraints, derived using the Kirovski et al. [5] algorithm. The coverage of COT+ created by combinatorial optimization is greater than that of mosaics, especially at larger lengths where even the simple greedy algorithm surpasses the mosaic coverage. Furthermore, the optimized COT+ coverage is almost identical to the coverage of constructs optimized with no collinearity constraints, indicating that the price for imposing a constraint on the immunogen to include a single virus-like strain is small. Figure 1 Comparison of Peptide Coverage Scores Achievable with Different Immunogen Formats and Algorithms Fischer and colleagues also argued that COT+ creates unnatural peptide sequences by concatenation. However, similar concatenation of their mosaics would have produced about 18 unnatural 9-mer peptides. Furthermore, the COT+ approach can be tuned to both penalize the introduction of unnatural peptides on concatenation, and to define the number of segments to be separately expressed, and thus reduce the requirement for concatenation. Several additional inferences were made in the response by Fischer et al. that should be commented upon. First, COT+ may, of course, be optimized for arbitrary HIV clades or combinations of clades, but the publication of our paper in PLoS Computational Biology reflects our focus on approaches to immunogen design rather than on the production of an exhaustive series of constructs. Also, just as in the mosaic approach, COT+ can be optimized to exclude rare variants (referred to as smoothing in our paper). Fischer et al. also discussed disappointing unpublished findings on the immunogenicity induced against Nef by a construct obtained by fusing a full-length Gag gene and the central portion of the Nef gene. However, these results can only be fairly assessed in light of what would be expected for the full-length Nef protein, and in the case of cellular immune responses, in the context of the same MHC specificities. However, these controls were not provided. We certainly agree that there are substantial challenges to the establishment of a multivalent CD8 response, yet multiple strategies have been and are being devised to overcome this important problem. For example, different groups have shown that CD8+ T cell responses can be successfully elicited against CD8+ T cell epitope strings when they are separated by short linker sequences and not in the context of the native protein, implying that they can be processed and presented in vivo [6–11]. Finally, despite 25 years of AIDS research and intensive yet uniformly failed efforts to develop an AIDS vaccine, the scientific community is poorly positioned to determine which, if any, approach to vaccine immunogen design will prove successful. Thus, arguing over methodologies developed with the same goal of incorporating variability has little significance as long as we do not know whether maximizing variability or inclusion of the entire full-length viral proteins are valid strategies. It may very well be that removing certain epitopes could be a more judicious approach than an overall epitope maximization strategy [12]. Indeed, the flexibility afforded by the COT+ approach, which is not limited to full-length proteins, may well prove superior to immunization with full-length viral protein immunogens.