Welcome to ShortScience.org! |
[link]
Lee et al. propose a variant of adversarial training where a generator is trained simultaneously to generated adversarial perturbations. This approach follows the idea that it is possible to “learn” how to generate adversarial perturbations (as in [1]). In this case, the authors use the gradient of the classifier with respect to the input as hint for the generator. Both generator and classifier are then trained in an adversarial setting (analogously to generative adversarial networks), see the paper for details. [1] Omid Poursaeed, Isay Katsman, Bicheng Gao, Serge Belongie. Generative Adversarial Perturbations. ArXiv, abs/1712.02328, 2017. |
[link]
This paper from 2016 introduced a new k-mer based method to estimate isoform abundance from RNA-Seq data called kallisto. The method provided a significant improvement in speed and memory usage compared to the previously used methods while yielding similar accuracy. In fact, kallisto is able to quantify expression in a matter of minutes instead of hours. The standard (previous) methods for quantifying expression rely on mapping, i.e. on the alignment of a transcriptome sequenced reads to a genome of reference. Reads are assigned to a position in the genome and the gene or isoform expression values are derived by counting the number of reads overlapping the features of interest. The idea behind kallisto is to rely on a pseudoalignment which does not attempt to identify the positions of the reads in the transcripts, only the potential transcripts of origin. Thus, it avoids doing an alignment of each read to a reference genome. In fact, kallisto only uses the transcriptome sequences (not the whole genome) in its first step which is the generation of the kallisto index. Kallisto builds a colored de Bruijn graph (T-DBG) from all the k-mers found in the transcriptome. Each node of the graph corresponds to a k-mer (a short sequence of k nucleotides) and retains the information about the transcripts in which they can be found in the form of a color. Linear stretches having the same coloring in the graph correspond to transcripts. Once the T-DBG is built, kallisto stores a hash table mapping each k-mer to its transcript(s) of origin along with the position within the transcript(s). This step is done only once and is dependent on a provided annotation file (containing the sequences of all the transcripts in the transcriptome). Then for a given sequenced sample, kallisto decomposes each read into its k-mers and uses those k-mers to find a path covering in the T-DBG. This path covering of the transcriptome graph, where a path corresponds to a transcript, generates k-compatibility classes for each k-mer, i.e. sets of potential transcripts of origin on the nodes. The potential transcripts of origin for a read can be obtained using the intersection of its k-mers k-compatibility classes. To make the pseudoalignment faster, kallisto removes redundant k-mers since neighboring k-mers often belong to the same transcripts. Figure1, from the paper, summarizes these different steps. https://i.imgur.com/eNH2kuO.png **Figure1**. Overview of kallisto. The input consists of a reference transcriptome and reads from an RNA-seq experiment. (a) An example of a read (in black) and three overlapping transcripts with exonic regions as shown. (b) An index is constructed by creating the transcriptome de Bruijn Graph (T-DBG) where nodes (v1, v2, v3, ... ) are k-mers, each transcript corresponds to a colored path as shown and the path cover of the transcriptome induces a k-compatibility class for each k-mer. (c) Conceptually, the k-mers of a read are hashed (black nodes) to find the k-compatibility class of a read. (d) Skipping (black dashed lines) uses the information stored in the T-DBG to skip k-mers that are redundant because they have the same k-compatibility class. (e) The k-compatibility class of the read is determined by taking the intersection of the k-compatibility classes of its constituent k-mers.[From Bray et al. Near-optimal probabilistic RNA-seq quantification, Nature Biotechnology, 2016.] Then, kallisto optimizes the following RNA-Seq likelihood function using the expectation-maximization (EM) algorithm. $$L(\alpha) \propto \prod_{f \in F} \sum_{t \in T} y_{f,t} \frac{\alpha_t}{l_t} = \prod_{e \in E}\left( \sum_{t \in e} \frac{\alpha_t}{l_t} \right )^{c_e}$$ In this function, $F$ is the set of fragments (or reads), $T$ is the set of transcripts, $l_t$ is the (effective) length of transcript $t$ and **y**$_{f,t}$ is a compatibility matrix defined as 1 if fragment $f$ is compatible with $t$ and 0 otherwise. The parameters $α_t$ are the probabilities of selecting reads from a transcript $t$. These $α_t$ are the parameters of interest since they represent the isoforms abundances or relative expressions. To make things faster, the compatibility matrix is collapsed (factorized) into equivalence classes. An equivalent class consists of all the reads compatible with the same subsets of transcripts. The EM algorithm is applied to equivalence classes (not to reads). Each $α_t$ will be optimized to maximise the likelihood of transcript abundances given observations of the equivalence classes. The speed of the method makes it possible to evaluate the uncertainty of the abundance estimates for each RNA-Seq sample using a bootstrap technique. For a given sample containing $N$ reads, a bootstrap sample is generated from the sampling of $N$ counts from a multinomial distribution over the equivalence classes derived from the original sample. The EM algorithm is applied on those sampled equivalence class counts to estimate transcript abundances. The bootstrap information is then used in downstream analyses such as determining which genes are differentially expressed. Practically, we can illustrate the different steps involved in kallisto using a small example. Starting from a tiny genome with 3 transcripts, assume that the RNA-Seq experiment produced 4 reads as depicted in the image below. https://i.imgur.com/5JDpQO8.png The first step is to build the T-DBG graph and the kallisto index. All transcript sequences are decomposed into k-mers (here k=5) to construct the colored de Bruijn graph. Not all nodes are represented in the following drawing. The idea is that each different transcript will lead to a different path in the graph. The strand is not taken into account, kallisto is strand-agnostic. https://i.imgur.com/4oW72z0.png Once the index is built, the four reads of the sequenced sample can be analysed. They are decomposed into k-mers (k=5 here too) and the pre-built index is used to determine the k-compatibility class of each k-mer. Then, the k-compatibility class of each read is computed. For example, for read 1, the intersection of all the k-compatibility classes of its k-mers suggests that it might come from transcript 1 or transcript 2. https://i.imgur.com/woektCH.png This is done for the four reads enabling the construction of the compatibility matrix **y**$_{f,t}$ which is part of the RNA-Seq likelihood function. In this equation, the $α_t$ are the parameters that we want to estimate. https://i.imgur.com/Hp5QJvH.png The EM algorithm being too slow to be applied on millions of reads, the compatibility matrix **y**$_{f,t}$ is factorized into equivalence classes and a count is computed for each class (how many reads are represented by this equivalence class). The EM algorithm uses this collapsed information to maximize the new equivalent RNA-Seq likelihood function and optimize the $α_t$. https://i.imgur.com/qzsEq8A.png The EM algorithm stops when for every transcript $t$, $α_tN$ > 0.01 changes less than 1%, where $N$ is the total number of reads. |
[link]
Nayebi and Ganguli propose saturating neural networks as defense against adversarial examples. The main observation driving this paper can be stated as follows: Neural networks are essentially based on linear sums of neurons (e.g. fully connected layers, convolutiona layers) which are then activated; by injecting a small amount of noise per neuron it is possible to shift the final sum by large values, thereby propagating the noisy through the network and fooling the network into misclassifying an example. To prevent the impact of these adversarial examples, the network should be trained in a manner to drive many neurons into a saturated regime – noisy will, so the argument, have less impact then. The authors also give a biological motivation, which I won't go into detail here. Letting $\psi$ be the used activation function, e.g. sigmoid or ReLU, a regularizer is added to drive neurons into saturation. In particular, a penalty $\lambda \sum_l \sum_i \psi_c(h_i^l)$ is added to the loss. Here, $l$ indexes the layer and $i$ the unit in the layer; $h_i^l$ then describes the input to the non-linearity computed for unit $i$ in layer $l$. $\psi_c$ is the complementary function defined as $\psi_c(z) = \inf_{z': \psi'(z') = 0} |z – z'|$ It defines the distance of the point $z$ to the nearest saturated point $z'$ where $\psi'(z') = 0$. For ReLU activations, the complementary function is the ReLU function itself; for sigmoid activations, the complementary function is $\sigma_c(z) = |\sigma(z)(1 - \sigma(z))|$. In experiments, Nayebi and Ganguli show that training with the additional penalty yields networks with higher robustness against adversarial examples compared to adversarial training (i.e. training on adversarial examples). They also provide some insight, showing e.g. the activation and weight distribution of layers illustrating that neurons are indeed saturated in large parts. For details, see the paper. I also want to point to a comment on the paper written by Brendel and Bethge [1] questioning the effectiveness of the proposed defense strategy. They discuss a variant of the fast sign gradient method (FSGM) with stabilized gradients which is able to fool saturated networks. [1] W. Brendel, M. Behtge. Comment on “Biologically inspired protection of deep networks from adversarial attacks”, https://arxiv.org/abs/1704.01547. Also find this summary at [davidstutz.de](https://davidstutz.de/category/reading/). |
[link]
A very simple (but impractical) discrete model of subclonal evolution would include the following events: * Division of a cell to create two cells: * **Mutation** at a location in the genome of the new cells * Cell death at a new timestep * Cell survival at a new timestep Because measurements of mutations are usually taken at one time point, this is taken to be at the end of a time series of these events, where a tiny of subset of cells are observed and a **genotype matrix** $A$ is produced, in which mutations and cells are arbitrarily indexed such that $A_{i,j} = 1$ if mutation $j$ exists in cell $i$. What this matrix allows us to see is the proportion of cells which *both have mutation $j$*. Unfortunately, I don't get to observe $A$, in practice $A$ has been corrupted by IID binary noise to produce $A'$. This paper focuses on difference inference problems given $A'$, including *inferring $A$*, which is referred to as **`noise_elimination`**. The other problems involve inferring only properties of the matrix $A$, which are referred to as: * **`noise_inference`**: predict whether matrix $A$ would satisfy the *three gametes rule*, which asks if a given genotype matrix *does not describe a branching phylogeny* because a cell has inherited mutations from two different cells (which is usually assumed to be impossible under the infinite sites assumption). This can be computed exactly from $A$. * **Branching Inference**: it's possible that all mutations are inherited between the cells observed; in which case there are *no branching events*. The paper states that this can be computed by searching over permutations of the rows and columns of $A$. The problem is to predict from $A'$ if this is the case. In both problems inferring properties of $A$, the authors use fully connected networks with two hidden layers on simulated datasets of matrices. For **`noise_elimination`**, computing $A$ given $A'$, the authors use a network developed for neural machine translation called a [pointer network][pointer]. They also find it necessary to map $A'$ to a matrix $A''$, turning every element in $A'$ to a fixed length row containing the location, mutation status and false positive/false negative rate. Unfortunately, reported results on real datasets are reported only for branching inference and are limited by the restriction on input dimension. The inferred branching probability reportedly matches that reported in the literature. [pointer]: https://arxiv.org/abs/1409.0473 |
[link]
Ongoing declines in production of the world's fisheries may have serious ecological and socioeconomic consequences. As a result, a number of international efforts have sought to improve management and prevent overexploitation, while helping to maintain biodiversity and a sustainable food supply. Although these initiatives have received broad acceptance, the extent to which corrective measures have been implemented and are effective remains largely unknown. We used a survey approach, validated with empirical data, and enquiries to over 13,000 fisheries experts (of which 1,188 responded) to assess the current effectiveness of fisheries management regimes worldwide; for each of those regimes, we also calculated the probable sustainability of reported catches to determine how management affects fisheries sustainability. Our survey shows that 7% of all coastal states undergo rigorous scientific assessment for the generation of management policies, 1.4% also have a participatory and transparent processes to convert scientific recommendations into policy, and 0.95% also provide for robust mechanisms to ensure the compliance with regulations; none is also free of the effects of excess fishing capacity, subsidies, or access to foreign fishing. A comparison of fisheries management attributes with the sustainability of reported fisheries catches indicated that the conversion of scientific advice into policy, through a participatory and transparent process, is at the core of achieving fisheries sustainability, regardless of other attributes of the fisheries. Our results illustrate the great vulnerability of the world's fisheries and the urgent need to meet well-identified guidelines for sustainable management; they also provide a baseline against which future changes can be quantified. Author Summary Top Global fisheries are in crisis: marine fisheries provide 15% of the animal protein consumed by humans, yet 80% of the world's fish stocks are either fully exploited, overexploited or have collapsed. Several international initiatives have sought to improve the management of marine fisheries, hoping to reduce the deleterious ecological and socioeconomic consequence of the crisis. Unfortunately, the extent to which countries are improving their management and whether such intervention ensures the sustainability of the fisheries remain unknown. Here, we surveyed 1,188 fisheries experts from every coastal country in the world for information about the effectiveness with which fisheries are being managed, and related those results to an index of the probable sustainability of reported catches. We show that the management of fisheries worldwide is lagging far behind international guidelines recommended to minimize the effects of overexploitation. Only a handful of countries have a robust scientific basis for management recommendations, and transparent and participatory processes to convert those recommendations into policy while also ensuring compliance with regulations. Our study also shows that the conversion of scientific advice into policy, through a participatory and transparent process, is at the core of achieving fisheries sustainability, regardless of other attributes of the fisheries. These results illustrate the benefits of participatory, transparent, and science-based management while highlighting the great vulnerability of the world's fisheries services. The data for each country can be viewed at http://as01.ucis.dal.ca/ramweb/surveys/fishery_assessment . |