bioRxiv Science⌕ Search

Biology subjects

Saei, A.

Publications and source records attributed to Saei, A..

3 recordsLinked to original sources

CoPISA: Combinatorial Proteome Integral Solubility/Stability Alteration analysis

Combination therapies are widely used in acute myeloid leukemia (AML), but systematic datasets capturing proteome-wide responses to multi-drug perturbations remain limited. Here we present CoPISA (Combinatorial Proteome Integral Solubility/Stability Alteration), a quantitative proteomics assay designed to profile protein solubility and stability responses to single and combined drug treatments. The dataset includes two AML drug pairs (LY3009120-sapanisertib and ruxolitinib-ulixertinib) applied to four AML cell lines (MOLM-13, MOLM-16, SKM-1, and NOMO-1) under control, single-agent, and combination conditions in both lysate and intact-cell formats. Thermal solubility profiling coupled with TMT-based multiplexed LC-MS/MS generated 16 TMT16-plex experiments comprising 192 LC-MS/MS raw files, providing deep proteome coverage across treatments and biological contexts. The resource includes raw and processed proteomics data, detailed experimental metadata in Sample and Data Relationship Format (SDRF), and reproducible analysis scripts for reporter normalization, protein-level aggregation, statistical modeling, and classification of combinatorial response patterns. The experimental design enables identification of proteins responding uniquely to combination treatments as well as overlapping single-agent effects. Technical validation demonstrates reproducible quantification across multiplex experiments and assay formats. All data are publicly available through the PRIDE repository (PXD066812) together with analysis code, enabling independent reanalysis and method development. This dataset provides a benchmark resource for studying proteome responses to drug combinations, comparing lysate and intact-cell perturbation profiles, developing computational approaches for combinatorial target inference, and supporting training in computational proteomics.

bioinformatics↗

Beyond the known cuts: trypsin specificity in native proteins

Trypsin is a serine protease that plays a pivotal role in protein digestion, being extensively used in various proteomics workflows due to its cleavage profile and specificity. Understanding trypsins enzymatic behavior is thus critical. We have employed Above-Filter Digestion Proteomics (AFDIP) to investigate trypsins cleavage preferences in HeLa cell lysates, preserving the proteins native state. We quantified over 18,000 unique peptides and correlated their emergence rates with cleavage window sequence motifs and physicochemical properties. Contrary to previous studies performed on denatured proteomes, we found that in native proteins cleavages at lysine residues were more abundant and faster than at arginine residues, and that physicochemical properties of the peptides affected their emergence times. These findings may need to be taken into account when interpreting the results of limited proteolysis experiments as well as when designing a food protein with extremely fast digestion times.

biochemistry↗

Chromosome-level Genome Assembly and Annotation of Petunia hybrida

Petunia hybrida is the worlds most popular garden plant and is regarded as a supermodel for studying the biology associated with the Asterid clade, the largest of the two major groups of flowering plants. Unlike other Solanaceae, petunia has a base chromosome number of seven, not 12. This along with recombination suppression has previously hindered efforts to assemble its genome to chromosome level. Here we achieve a chromosome-level assembly for P. hybrida using a combination of short-read and long-read sequencing, optical mapping (Bionano) and Hi-C technologies. The resulting assembly spans 1253.6 Mb with a BUSCO score of 99.8%. A total of 35,089 genes were predicted and of those 29,655 were functionally annotated. Syntenic regions between petunia, tomato and pepper were identified, highlighting rearrangements that have occurred since their divergence indicating that the 12 chromosomes of Solanaceae did not originate from whole genome duplication of an ancestral species with seven chromosomes like petunia. This chromosome-level assembly will significantly enhance trait mapping efficiency in petunia and serve as a valuable resource for functional genomic studies in this key plant model.

genomics↗