The third major opportunity comes from recent advances in mass spectrometry, such as the abovementioned timsTOF Pro and Astral instruments, whose improved sensitivity improves the number of high-quality spectra acquired from complex samples, essential for de novo sequencing. The timsTOF Pro combines trapped ion mobility spectrometry (TIMS) with parallel accumulation-serial fragmentation (PASEF), producing cleaner spectra with more finely resolved peaks, which reduces misidentifications and enhances peptide predictions. Similarly, the Astral offers ultra-high mass accuracy and resolution, enabling the detection of lowabundance peptides, thereby expanding proteome coverage. These instruments, along with orthogonal separation techniques like ion mobility spectrometry, help reduce spectral overlap and noise, allowing improved peptide identification and PTM detection. Moreover, in silico efforts such as filtering spectra based on quality metrics, such as signal-to-noise ratios , is therefore crucial for maximizing the accuracy of de novo sequencing. Additionally, clustering spectra into consensus representations can yield more comprehensive ion series information . Notably, clustering MS/MS data has proven effective for rapid quantitative profiling of metaproteomic samples, reducing the need for extensive database searches .