Source author record

Antti Honkela

Antti Honkela appears in the imported research catalog. Authorship, coauthor and topic links are available while profile ownership is still unclaimed.

ResearcherUnclaimed source record

Catalog footprint

What is connected

22works
13topics
4close collaborators

Actions

Connect this record

Log in to claim

Research graph

See the researcher in context

Open full explorer

Inspect adjacent papers, topics, institutions and collaborators without losing the researcher page.

Building this map preview

BZPEER is loading the nearby papers, people, topics and institutions for this page.

Published work

22 published item(s)

preprint2026arXiv

Beyond Square Roots: Explicit Memory-Efficient Factorization for Multi-Epoch Private Learning

Correlated-noise mechanisms are among the most promising approaches for improving the utility of differentially private model training, but rigorous guarantees require explicit, analyzable factorizations, and practical deployment requires memory efficiency. Recent works have developed banded inverse factorizations, which address both requirements by exploiting a banded structure in the correlation matrix. The bandwidth controls the size of the noise buffer used to correlate noise across iterations, and thus governs the tradeoff between utility and memory cost. Existing factorizations highlight this tradeoff: DP-$λ$CGD achieves high memory efficiency by using only a one-step noise buffer, but this limits its utility gains, while the banded inverse square root (BISR) factorization exploits larger correlation windows and is asymptotically optimal for large bandwidths but performs poorly at low bandwidths. We propose $γ$-BIFR, a unified generalization of both factorizations. In the low-memory, low-bandwidth regime, $γ$-BIFR significantly improves RMSE, amplified RMSE, and private training performance, while yielding tighter theoretical guarantees for multi-participation error in multi-epoch training.

preprint2026arXiv

Efficient and Scalable Implementation of Differentially Private Deep Learning without Shortcuts

Differentially private stochastic gradient descent (DP-SGD) is the standard algorithm for training machine learning models under differential privacy (DP). The most common DP-SGD privacy accountants rely on Poisson subsampling to ensure the theoretical DP guarantees. Implementing computationally efficient DP-SGD with Poisson subsampling is not trivial, which leads many implementations to taking a shortcut by using computationally faster subsampling. We quantify the computational cost of training deep learning models under DP by implementing and benchmarking efficient methods with the correct Poisson subsampling. We find that using the naive implementation of DP-SGD with Opacus in PyTorch has a throughput between 2.6 and 8 times lower than that of SGD. However, efficient gradient clipping implementations like Ghost Clipping can roughly halve this cost. We propose an alternative computationally efficient implementation of DP-SGD with JAX that uses Poisson subsampling and performs comparably with efficient clipping optimizations based on PyTorch. We study the scaling behavior using up to 80 GPUs and find that DP-SGD scales better than SGD. We share our library at https://github.com/DPBayes/Towards-Efficient-Scalable-Training-DP-DL.

preprint2022arXiv

Privacy-preserving Data Sharing on Vertically Partitioned Data

In this work, we introduce a differentially private method for generating synthetic data from vertically partitioned data, \emph{i.e.}, where data of the same individuals is distributed across multiple data holders or parties. We present a differentially privacy stochastic gradient descent (DP-SGD) algorithm to train a mixture model over such partitioned data using variational inference. We modify a secure multiparty computation (MPC) framework to combine MPC with differential privacy (DP), in order to use differentially private MPC effectively to learn a probabilistic generative model under DP on such vertically partitioned data. Assuming the mixture components contain no dependencies across different parties, the objective function can be factorized into a sum of products of the contributions calculated by the parties. Finally, MPC is used to compute the aggregate between the different contributions. Moreover, we rigorously define the privacy guarantees with respect to the different players in the system. To demonstrate the accuracy of our method, we run our algorithm on the Adult dataset from the UCI machine learning repository, where we obtain comparable results to the non-partitioned case.

preprint2022arXiv

Tight Accounting in the Shuffle Model of Differential Privacy

Shuffle model of differential privacy is a novel distributed privacy model based on a combination of local privacy mechanisms and a secure shuffler. It has been shown that the additional randomisation provided by the shuffler improves privacy bounds compared to the purely local mechanisms. Accounting tight bounds, however, is complicated by the complexity brought by the shuffler. The recently proposed numerical techniques for evaluating $(\varepsilon,δ)$-differential privacy guarantees have been shown to give tighter bounds than commonly used methods for compositions of various complex mechanisms. In this paper, we show how to obtain accurate bounds for adaptive compositions of general $\varepsilon$-LDP shufflers using the analysis by Feldman et al. (2021) and tight bounds for adaptive compositions of shufflers of $k$-randomised response mechanisms, using the analysis by Balle et al. (2019). We show how to speed up the evaluation of the resulting privacy loss distribution from $\mathcal{O}(n^2)$ to $\mathcal{O}(n)$, where $n$ is the number of users, without noticeable change in the resulting $δ(\varepsilon)$-upper bounds. We also demonstrate looseness of the existing bounds and methods found in the literature, improving previous composition results significantly.

preprint2021arXiv

D3p -- A Python Package for Differentially-Private Probabilistic Programming

We present d3p, a software package designed to help fielding runtime efficient widely-applicable Bayesian inference under differential privacy guarantees. d3p achieves general applicability to a wide range of probabilistic modelling problems by implementing the differentially private variational inference algorithm, allowing users to fit any parametric probabilistic model with a differentiable density function. d3p adopts the probabilistic programming paradigm as a powerful way for the user to flexibly define such models. We demonstrate the use of our software on a hierarchical logistic regression example, showing the expressiveness of the modelling approach as well as the ease of running the parameter inference. We also perform an empirical evaluation of the runtime of the private inference on a complex model and find a $\sim$10 fold speed-up compared to an implementation using TensorFlow Privacy.

preprint2020arXiv

Differentially private cross-silo federated learning

Strict privacy is of paramount importance in distributed machine learning. Federated learning, with the main idea of communicating only what is needed for learning, has been recently introduced as a general approach for distributed learning to enhance learning and improve security. However, federated learning by itself does not guarantee any privacy for data subjects. To quantify and control how much privacy is compromised in the worst-case, we can use differential privacy. In this paper we combine additively homomorphic secure summation protocols with differential privacy in the so-called cross-silo federated learning setting. The goal is to learn complex models like neural networks while guaranteeing strict privacy for the individual data subjects. We demonstrate that our proposed solutions give prediction accuracy that is comparable to the non-distributed setting, and are fast enough to enable learning models with millions of parameters in a reasonable time. To enable learning under strict privacy guarantees that need privacy amplification by subsampling, we present a general algorithm for oblivious distributed subsampling. However, we also argue that when malicious parties are present, a simple approach using distributed Poisson subsampling gives better privacy. Finally, we show that by leveraging random projections we can further scale-up our approach to larger models while suffering only a modest performance loss.

preprint2019arXiv

Computing Tight Differential Privacy Guarantees Using FFT

Differentially private (DP) machine learning has recently become popular. The privacy loss of DP algorithms is commonly reported using $(\varepsilon,δ)$-DP. In this paper, we propose a numerical accountant for evaluating the privacy loss for algorithms with continuous one dimensional output. This accountant can be applied to the subsampled multidimensional Gaussian mechanism which underlies the popular DP stochastic gradient descent. The proposed method is based on a numerical approximation of an integral formula which gives the exact $(\varepsilon,δ)$-values. The approximation is carried out by discretising the integral and by evaluating discrete convolutions using the fast Fourier transform algorithm. We give both theoretical error bounds and numerical error estimates for the approximation. Experimental comparisons with state-of-the-art techniques demonstrate significant improvements in bound tightness and/or computation time. Python code for the method can be found in Github (https://github.com/DPBayes/PLD-Accountant/).

preprint2019arXiv

Learning Rate Adaptation for Federated and Differentially Private Learning

We propose an algorithm for the adaptation of the learning rate for stochastic gradient descent (SGD) that avoids the need for validation set use. The idea for the adaptiveness comes from the technique of extrapolation: to get an estimate for the error against the gradient flow which underlies SGD, we compare the result obtained by one full step and two half-steps. The algorithm is applied in two separate frameworks: federated and differentially private learning. Using examples of deep neural networks we empirically show that the adaptive algorithm is competitive with manually tuned commonly used optimisation methods for differentially privately training. We also show that it works robustly in the case of federated learning unlike commonly used optimisation methods.

preprint2016arXiv

Analysis of differential splicing suggests different modes of short-term splicing regulation

Motivation: Alternative splicing is an important mechanism in which the regions of pre-mRNAs are differentially joined in order to form different transcript isoforms. Alternative splicing is involved in the regulation of normal physiological functions but also linked to the development of diseases such as cancer. We analyse differential expression and splicing using RNA-seq time series in three different settings: overall gene expression levels, absolute transcript expression levels and relative transcript expression levels. Results: Using estrogen receptor $α$ signalling response as a model system, our Gaussian process (GP)-based test identifies genes with differential splicing and/or differentially expressed transcripts. We discover genes with consistent changes in alternative splicing independent of changes in absolute expression and genes where some transcripts change while others stay constant in absolute level. The results suggest classes of genes with different modes of alternative splicing regulation during the experiment. Availability: R and Matlab codes implementing the method are available at https://github.com/PROBIC/diffsplicing . An interactive browser for viewing all model fits is available at http://users.ics.aalto.fi/hande/splicingGP/ .

preprint2016arXiv

Bayesian identification of bacterial strains from sequencing data

Rapidly assaying the diversity of a bacterial species present in a sample obtained from a hospital patient or an evironmental source has become possible after recent technological advances in DNA sequencing. For several applications it is important to accurately identify the presence and estimate relative abundances of the target organisms from short sequence reads obtained from a sample. This task is particularly challenging when the set of interest includes very closely related organisms, such as different strains of pathogenic bacteria, which can vary considerably in terms of virulence, resistance and spread. Using advanced Bayesian statistical modelling and computation techniques we introduce a novel pipeline for bacterial identification that is shown to outperform the currently leading pipeline for this purpose. Our approach enables fast and accurate sequence-based identification of bacterial strains while using only modest computational resources. Hence it provides a useful tool for a wide spectrum of applications, including rapid clinical diagnostics to distinguish among closely related strains causing nosocomial infections. The software implementation is available at https://github.com/PROBIC/BIB

preprint2016arXiv

On the inconsistency of $\ell_1$-penalised sparse precision matrix estimation

Various $\ell_1$-penalised estimation methods such as graphical lasso and CLIME are widely used for sparse precision matrix estimation. Many of these methods have been shown to be consistent under various quantitative assumptions about the underlying true covariance matrix. Intuitively, these conditions are related to situations where the penalty term will dominate the optimisation. In this paper, we explore the consistency of $\ell_1$-based methods for a class of sparse latent variable -like models, which are strongly motivated by several types of applications. We show that all $\ell_1$-based methods fail dramatically for models with nearly linear dependencies between the variables. We also study the consistency on models derived from real gene expression data and note that the assumptions needed for consistency never hold even for modest sized gene networks and $\ell_1$-based methods also become unreliable in practice for larger networks.

preprint2015arXiv

Fast and accurate approximate inference of transcript expression from RNA-seq data

Motivation: Assigning RNA-seq reads to their transcript of origin is a fundamental task in transcript expression estimation. Where ambiguities in assignments exist due to transcripts sharing sequence, e.g. alternative isoforms or alleles, the problem can be solved through probabilistic inference. Bayesian methods have been shown to provide accurate transcript abundance estimates compared to competing methods. However, exact Bayesian inference is intractable and approximate methods such as Markov chain Monte Carlo (MCMC) and Variational Bayes (VB) are typically used. While providing a high degree of accuracy and modelling flexibility, standard implementations can be prohibitively slow for large datasets and complex transcriptome annotations. Results: We propose a novel approximate inference scheme based on VB and apply it to an existing model of transcript expression inference from RNA-seq data. Recent advances in VB algorithmics are used to improve the convergence of the algorithm beyond the standard Variational Bayes Expectation Maximisation (VBEM) algorithm. We apply our algorithm to simulated and biological datasets, demonstrating a significant increase in speed with only very small loss in accuracy of expression level estimation. We carry out a comparative study against seven popular alternative methods and demonstrate that our new algorithm provides excellent accuracy and inter-replicate consistency while remaining competitive in computation time. Availability: The methods were implemented in R and C++, and are available as part of the BitSeq project at \url{https://github.com/BitSeq}. The method is also available through the BitSeq Bioconductor package. The source code to reproduce all simulation results can be accessed via \url{https://github.com/BitSeq/BitSeqVB_benchmarking}.

preprint2015arXiv

Fast Approximate Inference of Transcript Expression Levels from RNA-seq Data

Motivation: The mapping of RNA-seq reads to their transcripts of origin is a fundamental task in transcript expression estimation and differential expression scoring. Where ambiguities in mapping exist due to transcripts sharing sequence, e.g. alternative isoforms or alleles, the problem becomes an instance of non-trivial probabilistic inference. Bayesian inference in such a problem is intractable and approximate methods must be used such as Markov chain Monte Carlo (MCMC) and Variational Bayes. Standard implementations of these methods can be prohibitively slow for large datasets and complex gene models. Results: We propose an approximate inference scheme based on Variational Bayes applied to an existing model of transcript expression inference from RNA-seq data. We apply recent advances in Variational Bayes algorithmics to improve the convergence of the algorithm beyond the standard variational expectation-maximisation approach. We apply our algorithm to simulated and biological datasets, demonstrating that the increase in speed requires only a small trade-off in accuracy of expression level estimation. Availability: The methods were implemented in R and C++, and are available as part of the BitSeq project at https://code.google.com/p/bitseq/. The methods will be made available through the BitSeq Bioconductor package at the next stable release.

preprint2015arXiv

Genome-wide modelling of transcription kinetics reveals patterns of RNA production delays

Genes with similar transcriptional activation kinetics can display very different temporal mRNA profiles due to differences in transcription time, degradation rate and RNA processing kinetics. Recent studies have shown that a splicing-associated RNA production delay can be significant. We introduce a joint model of transcriptional activation and mRNA accumulation which can be used for inference of transcription rate, RNA production delay and degradation rate given genome-wide data from high-throughput sequencing time course experiments. We combine a mechanistic differential equation model with a non-parametric statistical modelling approach allowing us to capture a broad range of activation kinetics, and use Bayesian parameter estimation to quantify the uncertainty in the estimates of the kinetic parameters. We apply the model to data from estrogen receptor (ER-α) activation in the MCF-7 breast cancer cell line. We use RNA polymerase II (pol-II) ChIP-Seq time course data to characterise transcriptional activation and mRNA-Seq time course data to quantify mature transcripts. We find that 11% of genes with a good signal in the data display a delay of more than 20 minutes between completing transcription and mature mRNA production. The genes displaying these long delays are significantly more likely to be short. We also find a statistical association between high delay and late intron retention in pre-mRNA data, indicating significant splicing-associated production delays in many genes.

preprint2014arXiv

Exploration and retrieval of whole-metagenome sequencing samples

Over the recent years, the field of whole metagenome shotgun sequencing has witnessed significant growth due to the high-throughput sequencing technologies that allow sequencing genomic samples cheaper, faster, and with better coverage than before. This technical advancement has initiated the trend of sequencing multiple samples in different conditions or environments to explore the similarities and dissimilarities of the microbial communities. Examples include the human microbiome project and various studies of the human intestinal tract. With the availability of ever larger databases of such measurements, finding samples similar to a given query sample is becoming a central operation. In this paper, we develop a content-based exploration and retrieval method for whole metagenome sequencing samples. We apply a distributed string mining framework to efficiently extract all informative sequence $k$-mers from a pool of metagenomic samples and use them to measure the dissimilarity between two samples. We evaluate the performance of the proposed approach on two human gut metagenome data sets as well as human microbiome project metagenomic samples. We observe significant enrichment for diseased gut samples in results of queries with another diseased sample and very high accuracy in discriminating between different body sites even though the method is unsupervised. A software implementation of the DSM framework is available at https://github.com/HIITMetagenomics/dsm-framework

preprint2014arXiv

Gaussian process test for high-throughput sequencing time series: application to experimental evolution

Motivation: Recent advances in high-throughput sequencing (HTS) have made it possible to monitor genomes in great detail. New experiments not only use HTS to measure genomic features at one time point but to monitor them changing over time with the aim of identifying significant changes in their abundance. In population genetics, for example, allele frequencies are monitored over time to detect significant frequency changes that indicate selection pressures. Previous attempts at analysing data from HTS experiments have been limited as they could not simultaneously include data at intermediate time points, replicate experiments and sources of uncertainty specific to HTS such as sequencing depth. Results: We present the beta-binomial Gaussian process (BBGP) model for ranking features with significant non-random variation in abundance over time. The features are assumed to represent proportions, such as proportion of an alternative allele in a population. We use the beta-binomial model to capture the uncertainty arising from finite sequencing depth and combine it with a Gaussian process model over the time series. In simulations that mimic the features of experimental evolution data, the proposed method clearly outperforms classical testing in average precision of finding selected alleles. We also present simulations exploring different experimental design choices and results on real data from Drosophila experimental evolution experiment in temperature adaptation. Availability: R software implementing the test is available at https://github.com/handetopa/BBGP

preprint2014arXiv

Inference of RNA Polymerase II Transcription Dynamics from Chromatin Immunoprecipitation Time Course Data

Gene transcription mediated by RNA polymerase II (pol-II) is a key step in gene expression. The dynamics of pol-II moving along the transcribed region influence the rate and timing of gene expression. In this work we present a probabilistic model of transcription dynamics which is fitted to pol-II occupancy time course data measured using ChIP-Seq. The model can be used to estimate transcription speed and to infer the temporal pol-II activity profile at the gene promoter. Model parameters are estimated using either maximum likelihood estimation or via Bayesian inference using Markov chain Monte Carlo sampling. The Bayesian approach provides confidence intervals for parameter estimates and allows the use of priors that capture domain knowledge, e.g. the expected range of transcription speeds, based on previous experiments. The model describes the movement of pol-II down the gene body and can be used to identify the time of induction for transcriptionally engaged genes. By clustering the inferred promoter activity time profiles, we are able to determine which genes respond quickly to stimuli and group genes that share activity profiles and may therefore be co-regulated. We apply our methodology to biological data obtained using ChIP-seq to measure pol-II occupancy genome-wide when MCF-7 human breast cancer cells are treated with estradiol (E2). The transcription speeds we obtain agree with those obtained previously for smaller numbers of genes with the advantage that our approach can be applied genome-wide. We validate the biological significance of the pol-II promoter activity clusters by investigating cluster-specific transcription factor binding patterns and determining canonical pathway enrichment. We find that rapidly induced genes are enriched for both estrogen receptor alpha (ER$α$) and FOXA1 binding in their proximal promoter regions.

preprint2014arXiv

Probe region expression estimation for RNA-seq data for improved microarray comparability

Rapidly growing public gene expression databases contain a wealth of data for building an unprecedentedly detailed picture of human biology and disease. This data comes from many diverse measurement platforms that make integrating it all difficult. Although RNA-sequencing (RNA-seq) is attracting the most attention, at present the rate of new microarray studies submitted to public databases far exceeds the rate of new RNA-seq studies. There is clearly a need for methods that make it easier to combine data from different technologies. In this paper, we propose a new method for processing RNA-seq data that yields gene expression estimates that are much more similar to corresponding estimates from microarray data, hence greatly improving cross-platform comparability. The method we call PREBS is based on estimating the expression from RNA-seq reads overlapping the microarray probe regions, and processing these estimates with microarray summarisation algorithm RMA. Using paired microarray and RNA-seq samples from TCGA LAML data set we show that PREBS expression estimates derived from RNA-seq are more similar to microarray-based expression estimates than those from other RNA-seq processing methods. In an experiment to retrieve paired microarray samples from a database using an RNA-seq query sample, gene signatures defined based on PREBS expression estimates were found to be much more accurate than those from other methods. PREBS also allows new ways of using RNA-seq data, such as expression estimation for microarray probe sets. An implementation of the proposed method is available in the Bioconductor package `prebs'.

preprint2012arXiv

A mixed model approach for joint genetic analysis of alternatively spliced transcript isoforms using RNA-Seq data

RNA-Seq technology allows for studying the transcriptional state of the cell at an unprecedented level of detail. Beyond quantification of whole-gene expression, it is now possible to disentangle the abundance of individual alternatively spliced transcript isoforms of a gene. A central question is to understand the regulatory processes that lead to differences in relative abundance variation due to external and genetic factors. Here, we present a mixed model approach that allows for (i) joint analysis and genetic mapping of multiple transcript isoforms and (ii) mapping of isoform-specific effects. Central to our approach is to comprehensively model the causes of variation and correlation between transcript isoforms, including the genomic background and technical quantification uncertainty. As a result, our method allows to accurately test for shared as well as transcript-specific genetic regulation of transcript isoforms and achieves substantially improved calibration of these statistical tests. Experiments on genotype and RNA-Seq data from 126 human HapMap individuals demonstrate that our model can help to obtain a more fine-grained picture of the genetic basis of gene expression variation.

preprint2012arXiv

Bayes Blocks: An Implementation of the Variational Bayesian Building Blocks Framework

A software library for constructing and learning probabilistic models is presented. The library offers a set of building blocks from which a large variety of static and dynamic models can be built. These include hierarchical models for variances of other variables and many nonlinear models. The underlying variational Bayesian machinery, providing for fast and robust estimation but being mathematically rather involved, is almost completely hidden from the user thus making it very easy to use the library. The building blocks include Gaussian, rectified Gaussian and mixture-of-Gaussians variables and computational nodes which can be combined rather freely.

preprint2012arXiv

Gaussian process modelling of multiple short time series

We present techniques for effective Gaussian process (GP) modelling of multiple short time series. These problems are common when applying GP models independently to each gene in a gene expression time series data set. Such sets typically contain very few time points. Naive application of common GP modelling techniques can lead to severe over-fitting or under-fitting in a significant fraction of the fitted models, depending on the details of the data set. We propose avoiding over-fitting by constraining the GP length-scale to values that focus most of the energy spectrum to frequencies below the Nyquist frequency corresponding to the sampling frequency in the data set. Under-fitting can be avoided by more informative priors on observation noise. Combining these methods allows applying GP methods reliably automatically to large numbers of independent instances of short time series. This is illustrated with experiments with both synthetic data and real gene expression data.

preprint2012arXiv

Identifying differentially expressed transcripts from RNA-seq data with biological variation

Motivation: High-throughput sequencing enables expression analysis at the level of individual transcripts. The analysis of transcriptome expression levels and differential expression estimation requires a probabilistic approach to properly account for ambiguity caused by shared exons and finite read sampling as well as the intrinsic biological variance of transcript expression. Results: We present BitSeq (Bayesian Inference of Transcripts from Sequencing data), a Bayesian approach for estimation of transcript expression level from RNA-seq experiments. Inferred relative expression is represented by Markov chain Monte Carlo (MCMC) samples from the posterior probability distribution of a generative model of the read data. We propose a novel method for differential expression analysis across replicates which propagates uncertainty from the sample-level model while modelling biological variance using an expression-level-dependent prior. We demonstrate the advantages of our method using simulated data as well as an RNA-seq dataset with technical and biological replication for both studied conditions. Availability: The implementation of the transcriptome expression estimation and differential expression analysis, BitSeq, has been written in C++.