Wavelet noise is an alternative to Perlin noise which reduces the problems of aliasing and detail loss that are encountered when Perlin noise is summed into a fractal. == Algorithm detail == The basic algorithm for 2-dimensional wavelet noise is as follows: Create an image, R {\displaystyle R} , filled with uniform white noise. Downsample R {\displaystyle R} to half-size to create R ↓ {\displaystyle R^{\downarrow }} , then upsample it back up to full size to create R ↓↑ {\displaystyle R^{\downarrow \uparrow }} . Subtract R ↓↑ {\displaystyle R^{\downarrow \uparrow }} from R {\displaystyle R} to create the end result, N {\displaystyle N} . This results in an image that contains all the information that cannot be represented at half-scale. From here, N {\displaystyle N} can be used similarly to Perlin noise to create fractal patterns.
Neural network Gaussian process
A Neural Network Gaussian Process (NNGP) is a Gaussian process (GP) obtained as the limit of a certain type of sequence of neural networks. Specifically, a wide variety of network architectures converges to a GP in the infinitely wide limit, in the sense of distribution. The concept constitutes an intensional definition, i.e., a NNGP is just a GP, but distinguished by how it is obtained. == Motivation == Bayesian networks are a modeling tool for assigning probabilities to events, and thereby characterizing the uncertainty in a model's predictions. Deep learning and artificial neural networks are approaches used in machine learning to build computational models which learn from training examples. Bayesian neural networks merge these fields. They are a type of neural network whose parameters and predictions are both probabilistic. While standard neural networks often assign high confidence even to incorrect predictions, Bayesian neural networks can more accurately evaluate how likely their predictions are to be correct. Computation in artificial neural networks is usually organized into sequential layers of artificial neurons. The number of neurons in a layer is called the layer width. When we consider a sequence of Bayesian neural networks with increasingly wide layers (see figure), they converge in distribution to a NNGP. This large width limit is of practical interest, since the networks often improve as layers get wider. And the process may give a closed form way to evaluate networks. NNGPs also appears in several other contexts: It describes the distribution over predictions made by wide non-Bayesian artificial neural networks after random initialization of their parameters, but before training; it appears as a term in neural tangent kernel prediction equations; it is used in deep information propagation to characterize whether hyperparameters and architectures will be trainable. It is related to other large width limits of neural networks. === Scope === The first correspondence result had been established in the 1995 PhD thesis of Radford M. Neal, then supervised by Geoffrey Hinton at University of Toronto. Neal cites David J. C. MacKay as inspiration, who worked in Bayesian learning. Today the correspondence is proven for: Single hidden layer Bayesian neural networks; deep fully connected networks as the number of units per layer is taken to infinity; convolutional neural networks as the number of channels is taken to infinity; transformer networks as the number of attention heads is taken to infinity; recurrent networks as the number of units is taken to infinity. In fact, this NNGP correspondence holds for almost any architecture: Generally, if an architecture can be expressed solely via matrix multiplication and coordinatewise nonlinearities (i.e., a tensor program), then it has an infinite-width GP. This in particular includes all feedforward or recurrent neural networks composed of multilayer perceptron, recurrent neural networks (e.g., LSTMs, GRUs), (nD or graph) convolution, pooling, skip connection, attention, batch normalization, and/or layer normalization. === Illustration === Every setting of a neural network's parameters θ {\displaystyle \theta } corresponds to a specific function computed by the neural network. A prior distribution p ( θ ) {\displaystyle p(\theta )} over neural network parameters therefore corresponds to a prior distribution over functions computed by the network. As neural networks are made infinitely wide, this distribution over functions converges to a Gaussian process for many architectures. The notation used in this section is the same as the notation used below to derive the correspondence between NNGPs and fully connected networks, and more details can be found there. The figure to the right plots the one-dimensional outputs z L ( ⋅ ; θ ) {\displaystyle z^{L}(\cdot ;\theta )} of a neural network for two inputs x {\displaystyle x} and x ∗ {\displaystyle x^{}} against each other. The black dots show the function computed by the neural network on these inputs for random draws of the parameters from p ( θ ) {\displaystyle p(\theta )} . The red lines are iso-probability contours for the joint distribution over network outputs z L ( x ; θ ) {\displaystyle z^{L}(x;\theta )} and z L ( x ∗ ; θ ) {\displaystyle z^{L}(x^{};\theta )} induced by p ( θ ) {\displaystyle p(\theta )} . This is the distribution in function space corresponding to the distribution p ( θ ) {\displaystyle p(\theta )} in parameter space, and the black dots are samples from this distribution. For infinitely wide neural networks, since the distribution over functions computed by the neural network is a Gaussian process, the joint distribution over network outputs is a multivariate Gaussian for any finite set of network inputs. == Discussion == === Infinitely wide fully connected network === This section expands on the correspondence between infinitely wide neural networks and Gaussian processes for the specific case of a fully connected architecture. It provides a proof sketch outlining why the correspondence holds, and introduces the specific functional form of the NNGP for fully connected networks. The proof sketch closely follows the approach by Novak and coauthors. ==== Network architecture specification ==== Consider a fully connected artificial neural network with inputs x {\displaystyle x} , parameters θ {\displaystyle \theta } consisting of weights W l {\displaystyle W^{l}} and biases b l {\displaystyle b^{l}} for each layer l {\displaystyle l} in the network, pre-activations (pre-nonlinearity) z l {\displaystyle z^{l}} , activations (post-nonlinearity) y l {\displaystyle y^{l}} , pointwise nonlinearity ϕ ( ⋅ ) {\displaystyle \phi (\cdot )} , and layer widths n l {\displaystyle n^{l}} . For simplicity, the width n L + 1 {\displaystyle n^{L+1}} of the readout vector z L {\displaystyle z^{L}} is taken to be 1. The parameters of this network have a prior distribution p ( θ ) {\displaystyle p(\theta )} , which consists of an isotropic Gaussian for each weight and bias, with the variance of the weights scaled inversely with layer width. This network is illustrated in the figure to the right, and described by the following set of equations: x ≡ input y l ( x ) = { x l = 0 ϕ ( z l − 1 ( x ) ) l > 0 z i l ( x ) = ∑ j W i j l y j l ( x ) + b i l W i j l ∼ N ( 0 , σ w 2 n l ) b i l ∼ N ( 0 , σ b 2 ) ϕ ( ⋅ ) ≡ nonlinearity y l ( x ) , z l − 1 ( x ) ∈ R n l × 1 n L + 1 = 1 θ = { W 0 , b 0 , … , W L , b L } {\displaystyle {\begin{aligned}x&\equiv {\text{input}}\\y^{l}(x)&=\left\{{\begin{array}{lcl}x&&l=0\\\phi \left(z^{l-1}(x)\right)&&l>0\end{array}}\right.\\z_{i}^{l}(x)&=\sum _{j}W_{ij}^{l}y_{j}^{l}(x)+b_{i}^{l}\\W_{ij}^{l}&\sim {\mathcal {N}}\left(0,{\frac {\sigma _{w}^{2}}{n^{l}}}\right)\\b_{i}^{l}&\sim {\mathcal {N}}\left(0,\sigma _{b}^{2}\right)\\\phi (\cdot )&\equiv {\text{nonlinearity}}\\y^{l}(x),z^{l-1}(x)&\in \mathbb {R} ^{n^{l}\times 1}\\n^{L+1}&=1\\\theta &=\left\{W^{0},b^{0},\dots ,W^{L},b^{L}\right\}\end{aligned}}} ==== ==== z l | y l {\displaystyle z^{l}|y^{l}} is a Gaussian process We first observe that the pre-activations z l {\displaystyle z^{l}} are described by a Gaussian process conditioned on the preceding activations y l {\displaystyle y^{l}} . This result holds even at finite width. Each pre-activation z i l {\displaystyle z_{i}^{l}} is a weighted sum of Gaussian random variables, corresponding to the weights W i j l {\displaystyle W_{ij}^{l}} and biases b i l {\displaystyle b_{i}^{l}} , where the coefficients for each of those Gaussian variables are the preceding activations y j l {\displaystyle y_{j}^{l}} . Because they are a weighted sum of zero-mean Gaussians, the z i l {\displaystyle z_{i}^{l}} are themselves zero-mean Gaussians (conditioned on the coefficients y j l {\displaystyle y_{j}^{l}} ). Since the z l {\displaystyle z^{l}} are jointly Gaussian for any set of y l {\displaystyle y^{l}} , they are described by a Gaussian process conditioned on the preceding activations y l {\displaystyle y^{l}} . The covariance or kernel of this Gaussian process depends on the weight and bias variances σ w 2 {\displaystyle \sigma _{w}^{2}} and σ b 2 {\displaystyle \sigma _{b}^{2}} , as well as the second moment matrix K l {\displaystyle K^{l}} of the preceding activations y l {\displaystyle y^{l}} , z i l ∣ y l ∼ G P ( 0 , σ w 2 K l + σ b 2 ) K l ( x , x ′ ) = 1 n l ∑ i y i l ( x ) y i l ( x ′ ) {\displaystyle {\begin{aligned}z_{i}^{l}\mid y^{l}&\sim {\mathcal {GP}}\left(0,\sigma _{w}^{2}K^{l}+\sigma _{b}^{2}\right)\\K^{l}(x,x')&={\frac {1}{n^{l}}}\sum _{i}y_{i}^{l}(x)y_{i}^{l}(x')\end{aligned}}} The effect of the weight scale σ w 2 {\displaystyle \sigma _{w}^{2}} is to rescale the contribution to the covariance matrix from K l {\displaystyle K^{l}} , while the bias is shared for all inputs, and so σ b 2 {\displaystyle \sigma _{b}^{2}} makes the z i l {\displaystyle z_{i}^{l}} for different datapoints more similar and
FrameNet
FrameNet is a group of online lexical databases based upon the theory of meaning known as Frame semantics, developed by linguist Charles J. Fillmore. The project's fundamental notion is simple: most words' meanings may be best understood in terms of a semantic frame, which is a description of a certain kind of event, connection, or item and its actors. As an illustration, the act of cooking usually requires the following: a cook, the food being cooked, a container to hold the food while it is being cooked, and a heating instrument. Within FrameNet, this act is represented by a frame named Apply_heat, and its components (Cook, Food, Container, and Heating_instrument), are referred to as frame elements (FEs). The Apply_heat frame also lists a number of words that represent it, known as lexical units (LUs), like fry, bake, boil, and broil. Other frames are simpler. For example, Placing only has an agent or cause, a theme—something that is placed—and the location where it is placed. Some frames are more complex, like Revenge, which contains more FEs (offender, injury, injured party, avenger, and punishment). As in the examples of Apply_heat and Revenge below, FrameNet's role is to define the frames and annotate sentences to demonstrate how the FEs fit syntactically around the word that elicits the frame. == Concepts == === Frames === A frame is a schematic representation of a situation involving various participants, props, and other conceptual roles. Examples of frame names are Being_born and Locative_relation. A frame in FrameNet contains a textual description of what it represents (a frame definition), associated frame elements, lexical units, example sentences, and frame-to-frame relations. === Frame elements === Frame elements (FE) provide additional information to the semantic structure of a sentence. Each frame has a number of core and non-core FEs which can be thought of as semantic roles. Core FEs are essential to the meaning of the frame while non-core FEs are generally descriptive (such as time, place, manner, etc.) For example: The only core FE of the Being_born frame is called Child; non-core FEs Time, Place, Means, etc. Core FEs of the Commerce_goods-transfer frame include the Seller, Buyer, and Goods, while non-core FEs include a Place, Purpose, etc. FrameNet includes shallow data on syntactic roles that frame elements play in the example sentences. For example, for a sentence like "She was born about AD 460", FrameNet would mark She as a noun phrase referring to the Child frame element, and "about AD 460" as a noun phrase corresponding to the Time frame element. Details of how frame elements can be realized in a sentence are important because this reveals important information about the subcategorization frames as well as possible diathesis alternations (e.g. "John broke the window" vs. "The window broke") of a verb. === Lexical units === Lexical units (LUs) are lemmas, with their part of speech, that evoke a specific frame. In other words, when an LU is identified in a sentence, that specific LU can be associated with its specific frame(s). For each frame, there may be many LUs associated to that frame, and also there may be many frames that share a specific LU; this is typically the case with LUs that have multiple word senses. Alongside the frame, each lexical unit is associated with specific frame elements by means of the annotated example sentences. For example, lexical units that evoke the Complaining frame (or more specific perspectivized versions of it, to be precise), include the verbs complain, grouse, lament, and others. === Example sentences === Frames are associated with example sentences and frame elements are marked within the sentences. Thus, the sentence She was born about AD 460 is associated with the frame Being_born, while She is marked as the frame element Child and "about AD 460" is marked as Time. From the start, the FrameNet project has been committed to looking at evidence from actual language use as found in text collections like the British National Corpus. Based on such example sentences, automatic semantic role labeling tools are able to determine frames and mark frame elements in new sentences. === Valences === FrameNet also exposes statistics on the valence of each frame; that is, the number and position of the frame elements within example sentences. The sentence She was born about AD 460 falls in the valence pattern NP Ext, INI --, NP Dep which occurs twice in the FrameNet's annotation report for the born.v lexical unit, namely: She was born about AD 460, daughter and granddaughter of Roman and Byzantine emperors, whose family had been prominent in Roman politics for over 700 years. He was soon posted to north Africa, and never met their only child, a daughter born 8 June 1941. === Frame relations === FrameNet additionally captures relationships between different frames using relations. These include the following: Inheritance: When one frame is a more specific version of another, more abstract, parent frame. Anything that is true about the parent frame must also be true about the child frame, and a mapping is specified between the frame elements of the parent and the frame elements of the child. Perspectivization: A neutral frame is connected to a frame with a specific perspective of the same scenario. For example, Commerce_transfer-goods is considered from the perspective of the buyer in Commerce_buy and from that of the seller in Commerce_sell. Subframe: Some frames refer to complex scenarios that consist of several individual states or events that can be described by separate frames. For example, Criminal_process is composed of Arrest, Trial, and so on. Precedence: This relation captures the temporal order that holds between subframes of a complex frame. For example, within the Cycle_of_life_and_death frame, the subframe Death is preceded by the subframe Being_born. Causative and Inchoative: These two relations mark, for causative- and inchoative-aspect frames, the separate stative frame they refer to. For example, the stative Position_on_a_scale (e.g. "She had a high salary") is described by the causative Cause_change_of_scalar_position (e.g. "She raised his salary") and by the inchoative Change_position_on_a_scale frame (e.g. "Her salary increased"). Using: This relation marks a frame that in some way involves another frame. For example, Judgment_communication uses both Judgment and Statement, but does not inherit from either of them because there is no clear correspondence of frame elements. See also: Connects frames that bear some resemblance but need to be distinguished carefully. == Applications == FrameNet has proven to be useful in a number of computational applications, because computers need additional knowledge in order to recognize that "John sold a car to Mary" and "Mary bought a car from John" describe essentially the same situation, despite using two quite different verbs, different prepositions and a different word order. FrameNet has been used in applications like question answering, paraphrasing, recognizing textual entailment, and information extraction, either directly or by means of Semantic Role Labeling tools. The first automatic system for Semantic Role Labeling (SRL, sometimes also referred to as "shallow semantic parsing") was developed by Daniel Gildea and Daniel Jurafsky based on FrameNet in 2002. Semantic Role Labeling has since become one of the standard tasks in natural language processing, with the latest version (1.7) of FrameNet now fully supported in the Natural Language Toolkit. Since frames are essentially semantic descriptions, they are similar across languages, and several projects have arisen over the years that have relied on the original FrameNet as the basis for additional non-English FrameNets, for Spanish, Japanese, German, and Polish, among others.
Vector quantization
Vector quantization (VQ) is a classical quantization technique from signal processing that allows the modeling of probability density functions by the distribution of prototype vectors. Developed in the early 1980s by Robert M. Gray, it was originally used for data compression. It works by dividing a large set of points (vectors) into groups having approximately the same number of points closest to them. Each group is represented by its centroid point, as in k-means and some other clustering algorithms. In simpler terms, vector quantization chooses a set of points to represent a larger set of points. The density matching property of vector quantization is powerful, especially for identifying the density of large and high-dimensional data. Since data points are represented by the index of their closest centroid, commonly occurring data have low error, and rare data high error. This is why VQ is suitable for lossy data compression. It can also be used for lossy data correction and density estimation. Vector quantization is based on the competitive learning paradigm, so it is closely related to the self-organizing map model and to sparse coding models used in deep learning algorithms such as autoencoder. == Training == One simple training algorithm for vector quantization is: Pick a sample point at random Move the nearest quantization vector centroid towards this sample point, by a small fraction of the distance Repeat A more sophisticated algorithm reduces the bias in the density matching estimation and ensures that all points are used, by including an extra sensitivity parameter: Increase each centroid's sensitivity s i {\displaystyle s_{i}} by a small amount Pick a sample point P {\displaystyle P} at random For each quantization vector centroid c i {\displaystyle c_{i}} , let d ( P , c i ) {\displaystyle d(P,c_{i})} denote the distance of P {\displaystyle P} and c i {\displaystyle c_{i}} Find the centroid c i {\displaystyle c_{i}} for which d ( P , c i ) − s i {\displaystyle d(P,c_{i})-s_{i}} is the smallest Move c i {\displaystyle c_{i}} towards P {\displaystyle P} by a small fraction of the distance Set s i {\displaystyle s_{i}} to zero Repeat It is desirable to use a cooling schedule to produce convergence: see Simulated annealing. Another simple method is LBG, which is based on k-means. The algorithm can be iteratively updated with "live" data, rather than by picking random points from a data set, but this will introduce some bias if the data are temporally correlated over many samples. == Applications == Vector quantization is used for lossy data compression, lossy data correction, pattern recognition, density estimation and clustering. Lossy data correction, or prediction, is used to recover data missing from some dimensions. It is done by finding the nearest group with the data dimensions available, then predicting the result based on the values for the missing dimensions, assuming that they will have the same value as the group's centroid. For density estimation, the area/volume that is closer to a particular centroid than to any other is inversely proportional to the density (due to the density matching property of the algorithm). === Use in data compression === Vector quantization, also called "block quantization" or "pattern matching quantization" is often used in lossy data compression. It works by encoding values from a multidimensional vector space into a finite set of values from a discrete subspace of lower dimension. A lower-space vector requires less storage space, so the data is compressed. Due to the density matching property of vector quantization, the compressed data has errors that are inversely proportional to density. The transformation is usually done by projection or by using a codebook. In some cases, a codebook can be also used to entropy code the discrete value in the same step, by generating a prefix coded variable-length encoded value as its output. The set of discrete amplitude levels is quantized jointly rather than each sample being quantized separately. Consider a k-dimensional vector [ x 1 , x 2 , . . . , x k ] {\displaystyle [x_{1},x_{2},...,x_{k}]} of amplitude levels. It is compressed by choosing the nearest matching vector from a set of n-dimensional vectors [ y 1 , y 2 , . . . , y n ] {\displaystyle [y_{1},y_{2},...,y_{n}]} , with n < k. All possible combinations of the n-dimensional vector [ y 1 , y 2 , . . . , y n ] {\displaystyle [y_{1},y_{2},...,y_{n}]} form the vector space to which all the quantized vectors belong. Only the index of the codeword in the codebook is sent instead of the quantized values. This conserves space and achieves more compression. Twin vector quantization (VQF) is part of the MPEG-4 standard dealing with time domain weighted interleaved vector quantization. === Video codecs based on vector quantization === Bink video Cinepak Daala is transform-based but uses pyramid vector quantization on transformed coefficients Digital Video Interactive: Production-Level Video and Real-Time Video Indeo Microsoft Video 1 QuickTime: Apple Video (RPZA) and Graphics Codec (SMC) Sorenson SVQ1 and SVQ3 Smacker video VQA format, used in many games The usage of video codecs based on vector quantization has declined significantly in favor of those based on motion compensated prediction combined with transform coding, e.g. those defined in MPEG standards, as the low decoding complexity of vector quantization has become less relevant. === Audio codecs based on vector quantization === AMR-WB+ CELP CELT (now part of Opus) is transform-based but uses pyramid vector quantization on transformed coefficients Codec 2 DTS G.729 iLBC Ogg Vorbis TwinVQ === Use in pattern recognition === VQ was also used in the eighties for speech and speaker recognition. Recently it has also been used for efficient nearest neighbor search and on-line signature recognition. In pattern recognition applications, one codebook is constructed for each class (each class being a user in biometric applications) using acoustic vectors of this user. In the testing phase the quantization distortion of a testing signal is worked out with the whole set of codebooks obtained in the training phase. The codebook that provides the smallest vector quantization distortion indicates the identified user. The main advantage of VQ in pattern recognition is its low computational burden when compared with other techniques such as dynamic time warping (DTW) and hidden Markov model (HMM). The main drawback when compared to DTW and HMM is that it does not take into account the temporal evolution of the signals (speech, signature, etc.) because all the vectors are mixed up. In order to overcome this problem a multi-section codebook approach has been proposed. The multi-section approach consists of modelling the signal with several sections (for instance, one codebook for the initial part, another one for the center and a last codebook for the ending part). === Use as clustering algorithm === As VQ is seeking for centroids as density points of nearby lying samples, it can be also directly used as a prototype-based clustering method: each centroid is then associated with one prototype. By aiming to minimize the expected squared quantization error and introducing a decreasing learning gain fulfilling the Robbins-Monro conditions, multiple iterations over the whole data set with a concrete but fixed number of prototypes converges to the solution of k-means clustering algorithm in an incremental manner. === Generative adversarial networks (GAN) === VQ has been used to quantize a feature representation layer in the discriminator of generative adversarial networks. The feature quantization (FQ) technique performs implicit feature matching. It improves the GAN training, and yields an improved performance on a variety of popular GAN models: BigGAN for image generation, StyleGAN for face synthesis, and U-GAT-IT for unsupervised image-to-image translation.
Nabil Ali
Nabil Ali Mohammed Abd AL Azeez (Arabic:نبيل علي) (3 January 1938 – 27 January 2016) was an Egyptian scientist, writer, and intellectual who worked in the field of natural language processing and computational linguistics. Ali is considered a pioneer of Arabic language computing, making significant innovations in early computational linguistics. == Education and career == Ali earned a bachelor's degree in Aeronautical Engineering in 1960, and a master's degree in 1967. In 1971, he earned a PhD in Aeronautics. From 1961 to 1972 Ali worked as an engineering officer in the Egyptian Air Force, specializing in maintenance and training. In 1972, he shifted focus to computing, and from 1972 to 1977 he worked as a computer manager at Egyptair. While in this position, Ali introduced the first automated reservation system for airlines in the Arab world. He later held various computing positions in Egypt, Kuwait, Europe, Canada and the US. Ali started working for Sakhr Software, an Arabic language technology company, in 1983. From 1985 to 1999, he was vice president of Sakhr's council for Research and Development. As a director of the Multilingual Advanced Systems Foundation and project manager at the Egyptian National Company for Scientific and Technical Information, Ali did extensive research on information culture and artificial intelligence relating to the Arabic language. Over the course of his career, Ali developed more than 20 educational programs relating to computational linguistics. He developed the first Arabic lexical database and the first knowledge base for Arabic poetry, as well as many other pieces of Arabic language software. == Awards == 1994: General Book Authority Award for Best Book (in the field of future studies). 2003: General Book Authority Award for Best Culture Book (in the field of "Challenges of the Information Age"). 2007: General Book Authority "Innovation in Information Technology" Award. 2012: King Faisal International Award, with Professor Ali Helmy Mousa, in the field of computer processing of the Arabic Language. == Works == Arabic Language and Computer (Research study), Dar Localization, 1988. Al Arab and the Information Age, Knowledge World Series No. 184, April 1994. Arab Culture and the Information Age: A Vision for the Future of Arab Culture Discourse, World of Knowledge Series, No. 265 January 2001. The Digital Gap: an Arab Vision for a Knowledge Society (in partnership with Dr. Nadia Hegazy), World of Knowledge Series, No. 318 August 2005. The Arab Mind and the Knowledge Society: Manifestations of the Crisis and Suggestions for Solutions, Part 1, The World of Knowledge Series, No. 369, November 2009. The Arab Mind and the Knowledge Society: Manifestations of the Crisis and Suggestions for Solutions, Part 2, The World of Knowledge Series, No. 370, December 2009. == Tribute == On 3 January 2020, Google Doodle celebrated Nabil Ali Mohamed's 82nd Birthday.
Symbol level
In knowledge-based systems, agents choose actions based on the principle of rationality to move closer to a desired goal. The agent is able to make decisions based on knowledge it has about the world (see knowledge level). But for the agent to actually change its state, it must use whatever means it has available. This level of description for the agent's behavior is the symbol level. The term was coined by Allen Newell in 1982. For example, in a computer program, the knowledge level consists of the information contained in its data structures that it uses to perform certain actions. The symbol level consists of the program's algorithms, the data structures themselves, and so on.
Multiple sequence alignment
Multiple sequence alignment (MSA) is the process or the result of sequence alignment of three or more biological sequences, generally protein, DNA, or RNA. These alignments are used to infer evolutionary relationships via phylogenetic analysis and can highlight homologous features between sequences. Alignments highlight mutation events such as point mutations (single amino acid or nucleotide changes), insertion mutations and deletion mutations, and alignments are used to assess sequence conservation and infer the presence and activity of protein domains, tertiary structures, secondary structures, and individual amino acids or nucleotides. Multiple sequence alignments require more sophisticated methodologies than pairwise alignments, as they are more computationally complex. Most multiple sequence alignment programs use heuristic methods rather than global optimization because identifying the optimal alignment between more than a few sequences of moderate length is prohibitively computationally expensive. However, heuristic methods generally cannot guarantee high-quality solutions and have been shown to fail to yield near-optimal solutions on benchmark test cases. == Problem statement == Given m {\displaystyle m} sequences S i {\displaystyle S_{i}} , i = 1 , ⋯ , m {\displaystyle i=1,\cdots ,m} similar to the form below: S := { S 1 = ( S 11 , S 12 , … , S 1 n 1 ) S 2 = ( S 21 , S 22 , ⋯ , S 2 n 2 ) ⋮ S m = ( S m 1 , S m 2 , … , S m n m ) {\displaystyle S:={\begin{cases}S_{1}=(S_{11},S_{12},\ldots ,S_{1n_{1}})\\S_{2}=(S_{21},S_{22},\cdots ,S_{2n_{2}})\\\,\,\,\,\,\,\,\,\,\,\vdots \\S_{m}=(S_{m1},S_{m2},\ldots ,S_{mn_{m}})\end{cases}}} A multiple sequence alignment is taken of this set of sequences S {\displaystyle S} by inserting any amount of gaps needed into each of the S i {\displaystyle S_{i}} sequences of S {\displaystyle S} until the modified sequences, S i ′ {\displaystyle S'_{i}} , all conform to length L ≥ max { n i ∣ i = 1 , … , m } {\displaystyle L\geq \max\{n_{i}\mid i=1,\ldots ,m\}} and no values in the sequences of S {\displaystyle S} of the same column consists of only gaps. The mathematical form of an MSA of the above sequence set is shown below: S ′ := { S 1 ′ = ( S 11 ′ , S 12 ′ , … , S 1 L ′ ) S 2 ′ = ( S 21 ′ , S 22 ′ , … , S 2 L ′ ) ⋮ S m ′ = ( S m 1 ′ , S m 2 ′ , … , S m L ′ ) {\displaystyle S':={\begin{cases}S'_{1}=(S'_{11},S'_{12},\ldots ,S'_{1L})\\S'_{2}=(S'_{21},S'_{22},\ldots ,S'_{2L})\\\,\,\,\,\,\,\,\,\,\,\vdots \\S'_{m}=(S'_{m1},S'_{m2},\ldots ,S'_{mL})\end{cases}}} To return from each particular sequence S i ′ {\displaystyle S'_{i}} to S i {\displaystyle S_{i}} , remove all gaps. == Graphing approach == A general approach when calculating multiple sequence alignments is to use graphs to identify all of the different alignments. When finding alignments via graph, a complete alignment is created in a weighted graph that contains a set of vertices and a set of edges. Each of the graph edges has a weight based on a certain heuristic that helps to score each alignment or subset of the original graph. === Tracing alignments === When determining the best suited alignments for each MSA, a trace is usually generated. A trace is a set of realized, or corresponding and aligned, vertices that has a specific weight based on the edges that are selected between corresponding vertices. When choosing traces for a set of sequences it is necessary to choose a trace with a maximum weight to get the best alignment of the sequences. == Alignment methods == There are various alignment methods used within multiple sequence to maximize scores and correctness of alignments. Each is usually based on a certain heuristic with an insight into the evolutionary process. Most try to replicate evolution to get the most realistic alignment possible to best predict relations between sequences. === Dynamic programming === A direct method for producing an MSA uses the dynamic programming technique to identify the globally optimal alignment solution. For proteins, this method usually involves two sets of parameters: a gap penalty and a substitution matrix assigning scores or probabilities to the alignment of each possible pair of amino acids based on the similarity of the amino acids' chemical properties and the evolutionary probability of the mutation. For nucleotide sequences, a similar gap penalty is used, but a much simpler substitution matrix, wherein only identical matches and mismatches are considered, is typical. The scores in the substitution matrix may be either all positive or a mix of positive and negative in the case of a global alignment, but must be both positive and negative, in the case of a local alignment. For n individual sequences, the naive method requires constructing the n-dimensional equivalent of the matrix formed in standard pairwise sequence alignment. The search space thus increases exponentially with increasing n and is also strongly dependent on sequence length. Expressed with the big O notation commonly used to measure computational complexity, a naïve MSA takes O(LengthNseqs) time to produce. To find the global optimum for n sequences this way has been shown to be an NP-complete problem. In 1989, based on Carrillo-Lipman Algorithm, Altschul introduced a practical method that uses pairwise alignments to constrain the n-dimensional search space. In this approach pairwise dynamic programming alignments are performed on each pair of sequences in the query set, and only the space near the n-dimensional intersection of these alignments is searched for the n-way alignment. The MSA program optimizes the sum of all of the pairs of characters at each position in the alignment (the so-called sum of pair score) and has been implemented in a software program for constructing multiple sequence alignments. In 2019, Hosseininasab and van Hoeve showed that by using decision diagrams, MSA may be modeled in polynomial space complexity. === Progressive alignment construction === The most widely used approach to multiple sequence alignments uses a heuristic search known as progressive technique (also known as the hierarchical or tree method) developed by Da-Fei Feng and Doolittle in 1987. Progressive alignment builds up a final MSA by combining pairwise alignments beginning with the most similar pair and progressing to the most distantly related. All progressive alignment methods require two stages: a first stage in which the relationships between the sequences are represented as a phylogenetic tree, called a guide tree, and a second step in which the MSA is built by adding the sequences sequentially to the growing MSA according to the guide tree. The initial guide tree is determined by an efficient clustering method such as neighbor-joining or unweighted pair group method with arithmetic mean (UPGMA), and may use distances based on the number of identical two-letter sub-sequences (as in FASTA rather than a dynamic programming alignment). Progressive alignments are not guaranteed to be globally optimal. The primary problem is that when errors are made at any stage in growing the MSA, these errors are then propagated through to the final result. Performance is also particularly bad when all of the sequences in the set are rather distantly related. Most modern progressive methods modify their scoring function with a secondary weighting function that assigns scaling factors to individual members of the query set in a nonlinear fashion based on their phylogenetic distance from their nearest neighbors. This corrects for non-random selection of the sequences given to the alignment program. Progressive alignment methods are efficient enough to implement on a large scale for many (100s to 1000s) sequences. A popular progressive alignment method has been the Clustal family. ClustalW is used extensively for phylogenetic tree construction, in spite of the author's explicit warnings that unedited alignments should not be used in such studies and as input for protein structure prediction by homology modeling. European Bioinformatics Institute (EMBL-EBI) announced that CLustalW2 will expire in August 2015. They recommend Clustal Omega which performs based on seeded guide trees and HMM profile-profile techniques for protein alignments. An alternative tool for progressive DNA alignments is multiple alignment using fast Fourier transform (MAFFT). Another common progressive alignment method named T-Coffee is slower than Clustal and its derivatives but generally produces more accurate alignments for distantly related sequence sets. T-Coffee calculates pairwise alignments by combining the direct alignment of the pair with indirect alignments that aligns each sequence of the pair to a third sequence. It uses the output from Clustal as well as another local alignment program LALIGN, which finds multiple regions of local alignment between two sequences. The resulting alignment and phylogenetic tree are used as a guide to produce new and more accurate w