# Informative Initialization and Kernel Selection Improves t-SNE for Biological Sequences

arXiv: https://arxiv.org/abs/2211.09263 · HTML: https://mlsanity.com/paper/2211.09263/

## Key facts

- Cited by 5 papers in the map (data through 14 Oct 2026).
- Builds on 8 of its 22 references that are in the map.
- First posted on arXiv 16 Nov 2022.

## Builds on (most cited first, 8 of 8)

- [Spike2Vec: An Efficient and Scalable Embedding Approach for COVID-19 Spike Sequences](https://mlsanity.com/paper/2109.05019/) (2021)
- [A k-mer Based Approach for SARS-CoV-2 Variant Identification](https://mlsanity.com/paper/2108.03465/) (2021)
- [PWM2Vec: An Efficient Embedding Approach for Viral Host Specification from Coronavirus Spike Sequences](https://mlsanity.com/paper/2201.02273/) (2022)
- [Efficient Approximate Kernel Based Spike Sequence Classification](https://mlsanity.com/paper/2209.04952/) (2022)
- [Effective and scalable clustering of SARS-CoV-2 sequences](https://mlsanity.com/paper/2108.08143/) (2021)
- [Robust Representation and Efficient Feature Selection Allows for Effective Clustering of SARS-CoV-2 Variants](https://mlsanity.com/paper/2110.09622/) (2021)
- [Stochastic Neighbor Embedding separates well-separated clusters](https://mlsanity.com/paper/1702.02670/) (2017)
- [Improving the Effectiveness and Efficiency of Stochastic Neighbour Embedding with Isolation Kernel](https://mlsanity.com/paper/1906.09744/) (2019)

## Built on by (most cited first, 5 of 5)

- [BioSequence2Vec: Efficient Embedding Generation For Biological Sequences](https://mlsanity.com/paper/2304.00291/) (2023)
- [ViralVectors: Compact and Scalable Alignment-free Virome Feature Generation](https://mlsanity.com/paper/2304.02891/) (2023)
- [Virus2Vec: Viral Sequence Classification Using Machine Learning](https://mlsanity.com/paper/2304.12328/) (2023)
- [Beyond Accuracy: Measuring Representation Capacity of Embeddings to Preserve Structural and Contextual Information](https://mlsanity.com/paper/2309.11294/) (2023)
- [How smoothing the affinity matrix affects neighborhood preservation in t-SNE](https://mlsanity.com/paper/2608.17190/) (2026)

## Abstract (arXiv)

The t-distributed stochastic neighbor embedding (t- SNE) is a method for interpreting high dimensional (HD) data by mapping each point to a low dimensional (LD) space (usually two-dimensional). It seeks to retain the structure of the data. An important component of the t-SNE algorithm is the initialization procedure, which begins with the random initialization of an LD vector. Points in this initial vector are then updated to minimize the loss function (the KL divergence) iteratively using gradient descent. This leads comparable points to attract one another while pushing dissimilar points apart. We believe that, by default, these algorithms should employ some form of informative initialization. Another essential component of the t-SNE is using a kernel matrix, a similarity matrix comprising the pairwise distances among the sequences. For t-SNE-based visualization, the Gaussian kernel is employed by default in the literature. However, we show that kernel selection can also play a crucial role in the performance of t-SNE. In this work, we assess the performance of t-SNE with various alternative initialization methods and kernels, using four different sets, out of which three are biological sequences (nucleotide, protein, etc.) datasets obtained from various sources, such as the well-known GISAID database for sequences of the SARS- CoV-2 virus. We perform subjective and objective assessments of these alternatives. We use the resulting t-SNE plots and k- ary neighborhood agreement (k-ANA) to evaluate and compare the proposed methods with the baselines. We show that by using different techniques, such as informed initialization and kernel matrix selection, that t-SNE performs significantly better. Moreover, we show that t-SNE also takes fewer iterations to converge faster with more intelligent initialization.